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Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of breast cancer

Abstrict

Novel markers for breast cancer that are both sensitive and accurate. These markers are overexpressed in breast cancer specifically, as opposed to normal breast tissue. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can correlate with a probable diagnosis of breast cancer. The markers of the present invention, alone or in combination, show a high degree of differential detection between breast cancer and non-cancerous states.

Claims

1. An isolated polynucleotide comprising a polynucleotide having a sequence of R11723_PEA.sub.--1_T5 (SEQ ID NO:560).

2. The isolated polynucleotide of claim 1, comprising a node having a sequence of: R11723_PEA.sub.--1_node.sub.--13(SEQ ID NO:562).

3. An isolated polypeptide comprising a polypeptide having a sequence of: R11723_PEA.sub.--1_P13 (SEQ ID NO:591).

4. The isolated polypeptide of claim 3, comprising a chimeric polypeptide encoding for R11723_PEA.sub.--1_P13 (SEQ ID NO:591), comprising a first amino acid sequence being at least 95% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO:886), which also corresponds to amino acids 1-63 of R11723_PEA.sub.--1_P13 (SEQ ID NO:591), and a second amino acid sequence being at least about 95% homologous to a polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1026) corresponding to amino acids 64-84 of R11723_PEA.sub.--1_P13 (SEQ ID NO:591), wherein said first and second amino acid sequences are contiguous and in a sequential order.

4. (canceled)

5. The isolated polynucleotide of claim 1, comprising an amplicon according to SEQ ID NO: 975.

6. A primer pair, comprising a pair of isolated oligonucleotides capable of amplifying said amplicon of claim 5.

7. The primer pair of claim 6, comprising a pair of isolated oligonucleotides: SEQ NOs 973 and 974.

8. An antibody capable of specifically binding to an epitope of an amino acid sequence (SEQ ID NO:591) of claim 3.

9. The antibody of claim 8, wherein said amino acid sequence comprises said tail (SEQ ID NO:1026) of claim 4.

10. The antibody of claim 8, wherein said antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein PSEC (SEQ ID NO:886).

11. A kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant according to claim 1.

12. The kit of claim 11, wherein said kit comprises a NAT-based technology.

13. The kit of claim 11, wherein said kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence according to claim 1.

14. The kit of claim 11, wherein said kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence according to claim 1.

12. (canceled)

13. (canceled)

14. (canceled)

15. The method of claim 26, wherein said detecting overexpression is performed with a NAT-based technology.

16. A method for detecting breast cancer, comprising detecting overexpression of a splice variant according to claim 3, wherein said detecting overexpression is performed with an immunoassay.

17. The method of claim 16, wherein said immunoassay comprises an antibody according to claim 8.

18. A biomarker capable of detecting breast cancer, comprising a nucleic acid sequence according to claim 1 or a fragment thereof, or an amino acid sequence according to claim 3 or a fragment thereof.

19. A method for screening for breast cancer, comprising detecting breast cancer cells with a biomarker according to claim 18.

20. A method for diagnosing breast cancer, comprising detecting breast cancer cells with a biomarker according to claim 18.

21. A method for monitoring disease progression and/or treatment efficacy and/or relapse of breast cancer, comprising detecting breast cancer cells with a biomarker according to claim 18.

22. A method of selecting a therapy for breast cancer, comprising detecting breast cancer cells with a biomarker according to claim 18 and selecting a therapy according to said detection.

23. The isolated polypeptide of claim 4, comprising a tail of R11723_PEA.sub.--1_P13 (SEQ ID NO:591), comprising a polypeptide being at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1026) in R11723_PEA.sub.--1_P13 (SEQ ID NO:591).

24. A kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant according to claim 3, said kit comprising an antibody according to claim 8.

25. The kit of claim 24, wherein said kit further comprises at least one reagent for performing an ELISA or a Western blot.

26. A method for detecting breast cancer, comprising detecting overexpression of a splice variant according to claim 1.

Description

CROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] THIS APPLICATION IS RELATED TO NOVEL NUCLEOTIDE AND AMINO ACID SEQUENCES, AND ASSAYS AND METHODS OF USE THEREOF FOR DIAGNOSIS OF BREAST CANCER, AND CLAIMS PRIORITY TO THE BELOW U.S. PROVISIONAL APPLICATIONS WHICH ARE INCORPORATED BY REFERENCE HEREIN:

[0002] APPLICATION NO. 60/620,916 FILED OCT. 22, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN COLON CANCER

[0003] APPLICATION NO. 60/628,123 FILED NOV. 17, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN COLON CANCER II

[0004] APPLICATION NO. 60/621,131 FILED OCT. 25, 2004--DIAGNOSTIC MARKERS FOR COLON CANCER, AND ASSAYS AND METHODS OF USE THEREOF

[0005] APPLICATION NO. 60/620,917 FILED OCT. 22, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN BREAST CANCER

[0006] APPLICATION NO. 60/628,101 FILED NOV. 17, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN BREAST CANCER II

[0007] APPLICATION NO. 60/620,874 FILED OCT. 22, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN OVARIAN CANCER

[0008] APPLICATION NO. 60/628,134 FILED NOV. 17, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN OVARIAN CANCER II

[0009] APPLICATION NO. 60/620,924 FILED OCT. 22, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN STOMACH CANCER

[0010] APPLICATION NO. 60/628,111 FILED NOV. 17, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN STOMACH CANCER II

[0011] APPLICATION NO. 60/620,853 FILED OCT. 22, 2004-28814--DIFFERENTIAL EXPRESSION OF MARKERS IN LUNG CANCER

[0012] APPLICATION NO. 60/628,112 FILED NOV. 17, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN LUNG CANCER II

[0013] APPLICATION NO. 60/620,974 FILED OCT. 22, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN PANCREATIC CANCER

[0014] APPLICATION NO. 60/628,145 FILED NOV. 17, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN PANCREATIC CANCER II

[0015] APPLICATION NO. 60/620,656 FILED OCT. 22, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN PROSTATE CANCER

[0016] APPLICATION NO. 60/628,251 FILED NOV. 17, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN PROSTATE CANCER II

[0017] APPLICATION NO. 60/620,975 FILED OCT. 22, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN BRAIN CANCER

[0018] APPLICATION NO. 60/628,178 FILED NOV. 17, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN BRAIN CANCER II

[0019] APPLICATION NO. 60/628,231 FILED NOV. 17, 2004--NOVEL DIAGNOSTIC SERUM MARKERS, AND ASSAYS AND METHODS OF USE THEREOF

[0020] APPLICATION NO. 60/620,918 FILED OCT. 22, 2004--DIAGNOSTIC MARKERS FOR RENAL CANCER, AND ASSAYS AND METHODS OF USE THEREOF

[0021] APPLICATION NO. 60/628,156 FILED NOV. 17, 2004--DIAGNOSTIC MARKERS FOR RENAL CANCER, AND ASSAYS AND METHODS OF USE THEREOF II

[0022] APPLICATION NO. 60/628,167 FILED NOV. 17, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN BLADDER CANCER II

[0023] APPLICATION NO. 60/621,004 FILED OCT. 22, 2004--DIFFERENTIAL EXPRESSION OF MARKERS IN SKIN AND EPITHELIAL CANCER II

[0024] APPLICATION NO. ----NA----- FILED NOV. 17, 2004--NOVEL DIAGNOSTIC MARKERS, AND ASSAYS AND METHODS OF USE THEREOF

[0025] APPLICATION NO. 60/539,129 FILED JAN. 27, 2004--METHODS AND SYSTEMS FOR ANNOTATING BIOMOLECULAR SEQUENCES

[0026] APPLICATION NO. 60/539,128 FILED JAN. 27, 2004--EVOLUTIONARY CONSERVED SPLICED SEQUENCES AND METHODS AND SYSTEMS FOR IDENTIFYING THEREOF

FIELD OF THE INVENTION

[0027] The present invention is related to novel nucleotide and protein sequences that are diagnostic markers for breast cancer, and assays and methods of use thereof.

BACKGROUND OF THE INVENTION

[0028] Breast cancer is the most commonly occurring cancer in women, comprising almost a third of all malignancies in females. It is the leading cause of death for women between the ages 40-55 in the United States and one out of 8 females in the United States will develop breast cancer at some point in her life.

[0029] The death rate from breast cancer has been slowly declining over the past decade, partially due do the usage of molecular markers that facilitate the discovery, tumor typing (and therefore choice of treatment), response to treatment and recurrence.

[0030] The most widely used serum markers for breast cancers are Mucin1 (measured as CA 15-3) and CEA (CarcinoEmbryonic Antigen). Mucin 1 (MUC1) is present on the apical surface of normal epithelial cells. Its extracellular domain consists of a heavily O-linked glycosylated peptide core made up of variable number of multiple repeats of 20 amino acid sequence referred to as VNTR (Variable Number Tandem Repeat). This variability results in natural polymorphism of MUC1. Each VNTR has five potential O-linkage sites. The breast cancer disease state alters the enzymes which glycosylate Mucin 1 and therefore the polysaccharide side chains of tumor associated MUC1 are generally shorter than those on the normally expressed molecule. Both aberrant and up-regulated expression of MUC1 are features of malignancy and MUC1 related markers are based on it. Though CA 15-3 is a broadly used marker for breast cancer, a combination of CA 15-3 and CEA is more sensitive than using a single marker.

[0031] For the purpose of monitoring therapeutic response, CA 15-3, CEA and ESR (Erythrocyte Sedimentation Rate) are used as a panel, leading to over 90% of patients biochemically assessable. Serum markers used to monitor therapeutic response in patients with metastatic breast cancer are associated with the "spike phenomenon". It is an initial transient rise of tumor marker levels which can be seen in up to 30% of responders in the first 3 months of commencing a therapy. It is important not to interpret this as a sign of disease progression leading to premature change of an effective therapy.

[0032] CA 27.29 is a new monoclonal antibody directed against a different part of MUC1 and it is a newer marker than CA 15-3. It detects a different glycosylation pattern of MUC1, as compared with CA 15-3. CA 27.29 is the first FDA-approved blood test for breast cancer recurrence. Because of superior sensitivity and specificity, CA 27.29 has supplanted CA 15-3 as the preferred tumor marker in breast cancer. The CA 27.29 level is elevated in approximately one third of women with early-stage breast cancer (stage I or II) and in two thirds of women with late-stage disease (stage III or IV). CA 27.29 lacks predictive value in the earliest stages of breast cancer and thus has no role in screening for or diagnosing the malignancy. CA 27.29 also can be found in patients with benign disorders of the breast, liver, and kidney, and in patients with ovarian cysts. However, CA 27.29 levels higher than 100 units per mL are rare in benign conditions.

[0033] Recently Estrogen 2 (beta) was shown to have a diagnostic role in breast cancer. It has been shown that the expression of the `cx` variant of Estrogen 2 is correlated with response to Hormone adjuvant therapy. In addition it has been shown it may assist in better characterization of ER-1 positive breast cancers (together with progesterone receptor).

[0034] HER-2 (also known as c-erbB2) is a membrane proto-oncogene with intrinsic tyrosine kinase activity. Tumor expressing HER-2 are associated with shorter survival, shorter time-to-relapse and an overall worse prognosis. Tumors expressing HER-2 can be targeted with Trastuzumab--a biological adjuvant therapy which blocks the growth promoting action of HER-2. The ImmunoHistoChemistry (IHC) and Fluorescence In Situ Hybridization (FISH) tests are used to detect HER2: 1.IHC: The most common test used to check HER2 status is an ImmunoHistoChemistry (IHC) test. The IHC test measures the protein made by the HER2 gene. 2.FISH: This test measures the number of copies of the HER2 gene present in the tumor cell.

[0035] Measurement of the extracellular domain of HER-2 has been reported to show a better assessment of response to chemotherapy than a biochemical index score based on measurement of CA 15.3, CEA and ESR in a small series of patient. That finding is yet to be confirmed in a larger group of patient with HER-2 expressing tumors.

[0036] Other molecular markers, mainly used for the diagnosis for cancers other than breast cancer were shown to have a diagnostic potential in breast cancer. For example, CA125 which is a major marker for ovarian cancer is also associated with breast cancer. High levels of CA 19-9, a major marker for colorectal and pancreatic cancers, can be found in breast cancer. Overall, these markers are not frequently used for the detection of breast cancer to due their inferiority compared with other markers already described.

[0037] Panels of markers for the diagnosis and typing of breast cancer are being used by pathologists, including both markers described above and additional markers, such as immunohistochemistry markers that have been shown to have a beneficial value for the diagnosis of breast cancer, including PCNA and Ki-67 are maybe the most important and highly used immunohistochemistry markers for breast cancer. Other markers as E-Cadherin, Cathepsin D and TFF1 are also used for that purpose.

[0038] Despite relevant research efforts and the identification of many putative good prognosticators, few of them are proving clinically useful for identifying patients at minimal risk of relapse, patients with a worse prognosis, or patients likely to benefit from specific treatments. Most of them, such as epidermal growth factor receptor, cyclin E, p53 (this mutation is present in approximately 40% of human breast cancers as an acquired defect), bcl-2, vascular endothelial growth factor, urokinase-type plasminogen activator-1 and the anti-apoptosis protein survivin, are suggested for possible inclusion in the category of biomarkers with a high level of clinico-laboratory effectiveness. However, no single biomarker was able to identify those patients with the best (or worst) prognosis or those patients who would be responsive to a given therapy. High level cyclin E expression has been associated with the initiation or progression of different human cancers, in particular breast cancer but also leukemia, lymphoma and others. Cyclin-E expression level in the breast cancer was found to be a very strong indicator for prognosis, stronger than any other biological marker.

[0039] There are some non-cancerous pathological conditions which represent an increased risk factor for development breast cancer. Non-limiting examples of these conditions include: [0040] Ductal hyperplasia without atypia. It is the most frequently encountered breast biopsy result that is associated with increased risk of future development of breast cancer (2 fold increased risk). In particular, the loss of expression of transforming growth factor beta receptor II in the affected epithelial cells is associated with an increased risk of invasive breast cancer. [0041] Atypical hyperplasia. Women having atypical hyperplasia with over-expression of HER-2 have a greater than 7-fold increased risk of developing invasive breast carcinoma, as compared with women with non-proliferative benign breast lesions and no evidence of HER-2 amplification.

[0042] These pathological conditions should be effectively diagnosed and monitored in order to facilitate early detection of breast cancer.

SUMMARY OF THE INVENTION

[0043] The background art does not teach or suggest markers for breast cancer that are sufficiently sensitive and/or accurate, alone or in combination.

[0044] The present invention overcomes these deficiencies of the background art by providing novel markers for breast cancer that are both sensitive and accurate. These markers are overexpressed in breast cancer specifically, as opposed to normal breast tissue. The measurement of these markers, alone or in combination, in patient (biological) samples provides information that the diagnostician can correlate with a probable diagnosis of breast cancer. The markers of the present invention, alone or in combination, show a high degree of differential detection between breast cancer and non-cancerous states.

[0045] According to preferred embodiments of the present invention, examples of suitable biological samples which may optionally be used with preferred embodiments of the present invention include but are not limited to blood, serum, plasma, blood cells, urine, sputum, saliva, stool, spinal fluid or CSF, lymph fluid, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, milk, neuronal tissue, breast tissue, any human organ or tissue, including any tumor or normal tissue, any sample obtained by lavage (for example of the bronchial system or of the breast ductal system), and also samples of in vivo cell culture constituents. In a preferred embodiment, the biological sample comprises breast tissue and/or a serum sample and/or a urine sample and/or a milk sample and/or any other tissue or liquid sample. The sample can optionally be diluted with a suitable eluant before contacting the sample to an antibody and/or performing any other diagnostic assay.

[0046] Information given in the text with regard to cellular localization was determined according to four different software programs: (i) tmhmm (from Center for Biological Sequence Analysis, Technical University of Denmark DTU, http://www.cbs.dtu.dk/services/TMHMM/TMHMM2.0b.guide.php) or (ii) tmpred (from EMBnet, maintained by the ISREC Bionformatics group and the LICR Information Technology Office, Ludwig Institute for Cancer Research, Swiss Institute of Bioinformatics, http://www.ch.embnet.org/software/TMPRED_form.html) for transmembrane region prediction; (iii) signalp_hmm or (iv) signalp_nn (both from Center for Biological Sequence Analysis, Technical University of Denmark DTU, http://www.cbs.dtu.dk/services/SignalP/background/prediction.php) for signal peptide prediction. The terms "signalp_hmm" and "signalp_nn" refer to two modes of operation for the program SignalP: hmm refers to Hidden Markov Model, while nn refers to neural networks. Localization was also determined through manual inspection of known protein localization and/or gene structure, and the use of heuristics by the individual inventor. In some cases for the manual inspection of cellular localization prediction inventors used the ProLoc computational platform [Einat Hazkani-Covo, Erez Levanon, Galit Rotman, Dan Graur and Amit Novik; (2004) "Evolution of multicellularity in metazoa: comparative analysis of the subcellular localization of proteins in Saccharomyces, Drosophila and Caenorhabditis." Cell Biology International 2004;28(3):171-8.], which predicts protein localization based on various parameters including, protein domains (e.g., prediction of trans-membranous regions and localization thereof within the protein), pI, protein length, amino acid composition, homology to pre-annotated proteins, recognition of sequence patterns which direct the protein to a certain organelle (such as, nuclear localization signal, NLS, mitochondria localization signal), signal peptide and anchor modeling and using unique domains from Pfam that are specific to a single compartment.

[0047] Information is given in the text with regard to SNPs (single nucleotide polymorphisms). A description of the abbreviations is as follows. "T.fwdarw.C", for example, means that the SNP results in a change at the position given in the table from T to C. Similarly, "M.fwdarw.Q", for example, means that the SNP has caused a change in the corresponding amino acid sequence, from methionine (M) to glutamine (Q). If, in place of a letter at the right hand side for the nucleotide sequence SNP, there is a space, it indicates that a frameshift has occurred. A frameshift may also be indicated with a hyphen (-). A stop codon is indicated with an asterisk at the right hand side (*). As part of the description of an SNP, a comment may be found in parentheses after the above description of the SNP itself. This comment may include an FTId, which is an identifier to a SwissProt entry that was created with the indicated SNP. An FTId is a unique and stable feature identifier, which allows construction of links directly from position-specific annotation in the feature table to specialized protein-related databases. The FTId is always the last component of a feature in the description field, as follows: FTId=XXX_number, in which XXX is the 3-letter code for the specific feature key, separated by an underscore from a 6-digit number. In the table of the amino acid mutations of the wild type proteins of the selected splice variants of the invention, the header of the first column is "SNP position(s) on amino acid sequence", representing a position of a known mutation on amino acid sequence. SNPs may optionally be used as diagnostic markers according to the present invention, alone or in combination with one or more other SNPs and/or any other diagnostic marker. Preferred embodiments of the present invention comprise such SNPs, including but not limited to novel SNPs on the known (WT or wild type) protein sequences given below, as well as novel nucleic acid and/or amino acid sequences formed through such SNPs, and/or any SNP on a variant amino acid and/or nucleic acid sequence described herein.

[0048] Information given in the text with regard to the Homology to the known proteins was determined by Smith-Waterman version 5.1.2 using special (non default) parameters as follows: TABLE-US-00001 model=sw.model GAPEXT=0 GAPOP=100.0 MATRIX=blosum100

[0049] Information is given with regard to overexpression of a cluster in cancer based on ESTs. A key to the p values with regard to the analysis of such overexpression is as follows: [0050] library-based statistics: P-value without including the level of expression in cell-lines (P1) [0051] library based statistics: P-value including the level of expression in cell-lines (P2) [0052] EST clone statistics: P-value without including the level of expression in cell-lines (SP1) [0053] EST clone statistics: predicted overexpression ratio without including the level of expression in cell-lines (R3) [0054] EST clone statistics: P-value including the level of expression in cell-lines (SP2) [0055] EST clone statistics: predicted overexpression ratio including the level of expression in cell-lines (R4)

[0056] Library-based statistics refer to statistics over an entire library, while EST clone statistics refer to expression only for ESTs from a particular tissue or cancer.

[0057] Information is given with regard to overexpression of a cluster in cancer based on microarrays. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. There are two types of microarray results: those from microarrays prepared according to a design by the present inventors, for which the microarray fabrication procedure is described in detail in Materials and Experimental Procedures section herein; and those results from microarrays using Affymetrix technology. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. For microarrays prepared according to a design by the present inventors, the probe name begins with the name of the cluster (gene), followed by an identifying number. Oligonucleotide microarray results taken from Affymetrix data were from chips available from Affymetrix Inc, Santa Clara, Calif., USA (see for example data regarding the Human Genome U133 (HG-U133) Set at www.affymetrix.com/products/arrays/specific/hgu133..affx; GeneChip Human Genome U133A 2.0 Array at www.affymetrix.com/products/arrays/specific/hgu133av2.affx; and Human Genome U133 Plus 2.0 Array at www.affymetrix.com/products/arrays/specific/hgu133plus.affx). The probe names follow the Affymetrix naming convention. The data is available from NCBI Gene Expression Omnibus (see www.ncbi.nlm.nih.gov/projects/geo/ and Edgar et al, Nucleic Acids Research, 2002, Vol. 30, No. 1207-210). The dataset (including results) is available from www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1133 for the Series GSE1133 database (published on March 2004); a reference to these results is as follows: Su et al (Proc Natl Acad Sci USA. Apr. 20, 2004;101(16):6062-7. Epub Apr. 09, 2004). The probes designed according to the present inventors are listed below. TABLE-US-00002 >Z21368_0_0_61857 AGTTCATCCTTCTTCAGTGTGACCAGTAAATTCTTCCCATACTCTTGAAG (SEQ ID NO:895) >HUMGRP5E_0_0_16630 GCTGATATGGAAGTTGGGGAATCTGAATTGCCAGAGAATCTTGGGAAGAG (SEQ ID NO:896) >HUMGRP5E_0_2_0 TCTCATAGAAGCAAAGGAGAACAGAAACCACCAGCCACCTCAACCCAAGG (SEQ ID NO:897) >HSENA78_0_1_0 TGAAGAGTGTGAGGAAAACCTATGTTTGCCGCTTAAGCTTTCAGCTCAGC (SEQ ID NO:898) >M85491_0_0_25999 GACATCTTTGCATATCATGTCAGAGCTATAACATCATTGTGGAGAAGCTC (SEQ ID NO:899) >M85491_0_14_0 GTCATGAAAATCAACACCGAGGTGCGGAGCTTCGGACCTGTGTCCCGCAG (SEQ ID NO:900) >HSSTROL3_0_0_12518 ATGAGAGTAACCTCACCCGTGCACTAGTTTACAGAGCATTCACTGCCCCA (SEQ ID NO:901) >HSSTROL3_0_0_12517 CAGAGATGAGAGCCTGGAGCATTGCAGATGCCAGGGACTTCACAAATGAA (SEQ ID NO:902) >HUMCA1XIA_0_0_14909 GCTGCAATCTAAGTTTCGGAATACTTATACCACTCCAGAAATAATCCTCG (SEQ ID NO:903) >HUMCA1XIA_0_18_0 TTCAGAACTGTTAACATCGCTGACGGGAAGTGGCATCGGGTAGCAATCAG (SEQ ID NO:904) >R20779_0_0_30670 CCGCGTTGCTTCTAGAGGCTGAATGCCTTTCAAATGGAGAAGGCTTCCAT (SEQ ID NO:905) >HSS100PCB_0_0_12280 CTCAAAATGAAACTCCCTCTCGCAGAGCACAATTCCAATTCGCTCTAAAA (SEQ ID NO:906) >HSCOC4_0_0_9892 AAGGACCAGAGTCCATGCCAAGACCACCCTTCAGCTTCCAAGGCCCTCCA (SEQ ID NO:907) >HSCOC4_0_39_0 ATCCTCCAGCCATGAGGCTGCTCTGGGGGCTGATCTGGGCATCCAGCTTC (SEQ ID NO:908) >HSCOC4_0_0_9883 CCTGTTTGCTCTGACACCAACTTCCTACCCTCTCAGCCTCAAAGTAACTC (SEQ ID NO:909) >HSCOC4_0_0_9885 GCTGAGGTGTGGCCGAGGACCTGACCATCTGGAAGTGTGAAAATCCCCTT (SEQ ID NO:910) >T11628_0_9_0 ACAAGATCCCCGTGAAGTACCTGGAGTTCATCTCGGAATGCATCATCCAG (SEQ ID NO:911) >T11628_0_0_45174 TAAACAATCAAAGAGCATGTTGGCCTGGTCCTTTGCTAGGTACTGTAGAG (SEQ ID NO:912) >T11628_0_0_45161 TGCCTCGCCACAATGGCACCTGCCCTAAAATAGCTTCCCATGTGAGGGCT (SEQ ID NO:913) >M78076_0_7_0 GAGAAGATGAACCCGCTGGAACAGTATGAGCGAAAGGTGAATGCGTCTGT (SEQ ID NO:914) >HSMUC1A_0_37_0 AAAAGGAGACTTCGGCTACCCAGAGAAGTTCAGTGCCCAGCTCTACTGAG (SEQ ID NO:915) >HSMUC1A_0_0_11364 AAAGGCTGGCATAGGGGGAGGTTTCCCAGGTAGAAGAAGAAGTGTCAGCA (SEQ ID NO:916) >HSMUC1A_0_0_11365 AATTAACCCTTTGAGAGCTGGCCAGGACTCTGGACTGATTACCCCAGCCT (SEQ ID NO:917)

[0058] The following list of abbreviations for tissues was used in the TAA histograms. The term "TAA" stands for "Tumor Associated Antigen", and the TAA histograms, given in the text, represent the cancerous tissue expression pattern as predicted by the biomarkers selection engine, as described in detail in examples 1-5 below. TABLE-US-00003 "BONE" for "bone"; "COL" for "colon"; "EPI" for "epithelial"; "GEN" for "general"; "LIVER" for "liver"; "LUN" for "lung"; "LYMPH" for "lymph nodes"; "MARROW" for "bone marrow"; "OVA" for "ovary"; "PANCREAS" for "pancreas"; "PRO" for "prostate"; "STOMACH" for "stomach"; "TCELL" for "T cells"; "THYROID" for "Thyroid"; "MAM" for "breast"; "BRAIN" for "brain"; "UTERUS" for "uterus"; "SKIN" for "skin"; "KIDNEY" for "kidney"; "MUSCLE" for "muscle"; "ADREN" for "adrenal"; "HEAD" for "head and neck"; "BLADDER" for "bladder";

[0059] It should be noted that the terms "segment", "seg" and "node" are used interchangeably in reference to nucleic acid sequences of the present invention, they refer to portions of nucleic acid sequences that were shown to have one or more properties as described below. They are also the building blocks that were used to construct complete nucleic acid sequences as described in greater detail below. Optionally and preferably, they are examples of oligonucleotides which are embodiments of the present invention, for example as amplicons, hybridization units and/or from which primers and/or complementary oligonucleotides may optionally be derived, and/or for any other use.

[0060] As used herein the phrase "breast cancer" refers to cancers of the breast or surrounding tissue, including but not limited to ductal carcinoma (in-situ or invasive), lobular carcinoma (in-situ or invasive), inflammatory breast cancer, mucinous carcinoma, tubular carcinoma, or Paget's disease of the nipple, as well as conditions that are indicative of a higher risk factor for later development of breast cancer, including but not limited to ductal hyperplasia without atypia and atypical hyperplasia, referred to herein collectively as "indicative conditions".

[0061] The term "marker" in the context of the present invention refers to a nucleic acid fragment, a peptide, or a polypeptide, which is differentially present in a sample taken from subjects (patients) having breast cancer (or one of the above indicative conditions) as compared to a comparable sample taken from subjects who do not have breast cancer (or one of the above indicative conditions).

[0062] The phrase "differentially present" refers to differences in the quantity of a marker present in a sample taken from patients having breast cancer (or one of the above indicative conditions) as compared to a comparable sample taken from patients who do not have breast cancer (or one of the above indicative conditions). For example, a nucleic acid fragment may optionally be differentially present between the two samples if the amount of the nucleic acid fragment in one sample is significantly different from the amount of the nucleic acid fragment in the other sample, for example as measured by hybridization and/or NAT-based assays. A polypeptide is differentially present between the two samples if the amount of the polypeptide in one sample is significantly different from the amount of the polypeptide in the other sample. It should be noted that if the marker is detectable in one sample and not detectable in the other, then such a marker can be considered to be differentially present.

[0063] As used herein the phrase "diagnostic" means identifying the presence or nature of a pathologic condition. Diagnostic methods differ in their sensitivity and specificity. The "sensitivity" of a diagnostic assay is the percentage of diseased individuals who test positive (percent of "true positives"). Diseased individuals not detected by the assay are "false negatives." Subjects who are not diseased and who test negative in the assay are termed "true negatives." The "specificity" of a diagnostic assay is 1 minus the false positive rate, where the "false positive" rate is defined as the proportion of those without the disease who test positive. While a particular diagnostic method may not provide a definitive diagnosis of a condition, it suffices if the method provides a positive indication that aids in diagnosis.

[0064] As used herein the phrase "diagnosing" refers to classifying a disease or a symptom, determining a severity of the disease, monitoring disease progression, forecasting an outcome of a disease and/or prospects of recovery. The term "detecting" may also optionally encompass any of the above.

[0065] Diagnosis of a disease according to the present invention can be effected by determining a level of a polynucleotide or a polypeptide of the present invention in a biological sample obtained from the subject, wherein the level determined can be correlated with predisposition to, or presence or absence of the disease. It should be noted that a "biological sample obtained from the subject" may also optionally comprise a sample that has not been physically removed from the subject, as described in greater detail below.

[0066] As used herein, the term "level" refers to expression levels of RNA and/or protein or to DNA copy number of a marker of the present invention.

[0067] Typically the level of the marker in a biological sample obtained from the subject is different (i.e., increased or decreased) from the level of the same variant in a similar sample obtained from a healthy individual (examples of biological samples are described herein).

[0068] Numerous well known tissue or fluid collection methods can be utilized to collect the biological sample from the subject in order to determine the level of DNA, RNA and/or polypeptide of the variant of interest in the subject.

[0069] Examples include, but are not limited to, fine needle biopsy, needle biopsy, core needle biopsy and surgical biopsy (e.g., brain biopsy), and lavage. Regardless of the procedure employed, once a biopsy/sample is obtained the level of the variant can be determined and a diagnosis can thus be made.

[0070] Determining the level of the same variant in normal tissues of the same origin is preferably effected along-side to detect an elevated expression and/or amplification and/or a decreased expression, of the variant as opposed to the normal tissues.

[0071] A "test amount" of a marker refers to an amount of a marker in a subject's sample that is consistent with a diagnosis of breast cancer (or one of the above indicative conditions). A test amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals).

[0072] A "control amount" of a marker can be any amount or a range of amounts to be compared against a test amount of a marker. For example, a control amount of a marker can be the amount of a marker in a patient with breast cancer (or one of the above indicative conditions) or a person without breast cancer (or one of the above indicative conditions). A control amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals). "Detect" refers to identifying the presence, absence or amount of the object to be detected.

[0073] A "label" includes any moiety or item detectable by spectroscopic, photo chemical, biochemical, immunochemical, or chemical means. For example, useful labels include .sup.32P, .sup.35S, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin-streptavadin, dioxigenin, haptens and proteins for which antisera or monoclonal antibodies are available, or nucleic acid molecules with a sequence complementary to a target. The label often generates a measurable signal, such as a radioactive, chromogenic, or fluorescent signal, that can be used to quantify the amount of bound label in a sample. The label can be incorporated in or attached to a primer or probe either covalently, or through ionic, van der Waals or hydrogen bonds, e.g., incorporation of radioactive nucleotides, or biotinylated nucleotides that are recognized by streptavadin. The label may be directly or indirectly detectable. Indirect detection can involve the binding of a second label to the first label, directly or indirectly. For example, the label can be the ligand of a binding partner, such as biotin, which is a binding partner for streptavadin, or a nucleotide sequence, which is the binding partner for a complementary sequence, to which it can specifically hybridize. The binding partner may itself be directly detectable, for example, an antibody may be itself labeled with a fluorescent molecule. The binding partner also may be indirectly detectable, for example, a nucleic acid having a complementary nucleotide sequence can be a part of a branched DNA molecule that is in turn detectable through hybridization with other labeled nucleic acid molecules (see, e.g., P. D. Fahrlander and A. Klausner, Bio/Technology 6:1165 (1988)). Quantitation of the signal is achieved by, e.g., scintillation counting, densitometry, or flow cytometry.

[0074] Exemplary detectable labels, optionally and preferably for use with immunoassays, include but are not limited to magnetic beads, fluorescent dyes, radiolabels, enzymes (e.g., horse radish peroxide, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic beads. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture.

[0075] "Immunoassay" is an assay that uses an antibody to specifically bind an antigen. The immunoassay is characterized by the use of specific binding properties of a particular antibody to isolate, target, and/or quantify the antigen.

[0076] The phrase "specifically (or selectively) binds" to an antibody or "specifically (or selectively) immunoreactive with," when referring to a protein or peptide (or other epitope), refers to a binding reaction that is determinative of the presence of the protein in a heterogeneous population of proteins and other biologics. Thus, under designated immunoassay conditions, the specified antibodies bind to a particular protein at least two times greater than the background (non-specific signal) and do not substantially bind in a significant amount to other proteins present in the sample. Specific binding to an antibody under such conditions may require an antibody that is selected for its specificity for a particular protein. For example, polyclonal antibodies raised to seminal basic protein from specific species such as rat, mouse, or human can be selected to obtain only those polyclonal antibodies that are specifically immunoreactive with seminal basic protein and not with other proteins, except for polymorphic variants and alleles of seminal basic protein. This selection may be achieved by subtracting out antibodies that cross-react with seminal basic protein molecules from other species. A variety of immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Antibodies, A Laboratory Manual (1988), for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity). Typically a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 to 100 times background.

[0077] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00004 Transcript Name T10888_PEA_1_T1 (SEQ ID NO: 1) T10888_PEA_1_T4 (SEQ ID NO: 2) T10888_PEA_1_T5 (SEQ ID NO: 3) T10888_PEA_1_T6 (SEQ ID NO: 4)

[0078] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00005 Segment Name T10888_PEA_1_node_11 (SEQ ID NO: 5) T10888_PEA_1_node_12 (SEQ ID NO: 6) T10888_PEA_1_node_17 (SEQ ID NO: 7) T10888_PEA_1_node_4 (SEQ ID NO: 8) T10888_PEA_1_node_6 (SEQ ID NO: 9) T10888_PEA_1_node_7 (SEQ ID NO: 10) T10888_PEA_1_node_9 (SEQ ID NO: 11) T10888_PEA_1_node_15 (SEQ ID NO: 12)

[0079] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below amino acid sequence comprising a sequence in the table below: TABLE-US-00006 Protein Name T10888_PEA_1_P2 (SEQ ID NO: 14) T10888_PEA_1_P4 (SEQ ID NO: 15) T10888_PEA_1_P5 (SEQ ID NO: 16) T10888_PEA_1_P6 (SEQ ID NO: 17)

[0080] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00007 Transcript Name T39971_T10 (SEQ ID NO: 18) T39971_T12 (SEQ ID NO: 19) T39971_T16 (SEQ ID NO: 20) T39971_T5 (SEQ ID NO: 21)

[0081] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00008 Segment Name T39971_node_0 (SEQ ID NO: 22) T39971_node_18 (SEQ ID NO: 23) T39971_node_21 (SEQ ID NO: 24) T39971_node_22 (SEQ ID NO: 25) T39971_node_23 (SEQ ID NO: 26) T39971_node_31 (SEQ ID NO: 27) T39971_node_33 (SEQ ID NO: 28) T39971_node_7 (SEQ ID NO: 29) T39971_node_1 (SEQ ID NO: 30) T39971_node_10 (SEQ ID NO: 31) T39971_node_11 (SEQ ID NO: 32) T39971_node_12 (SEQ ID NO: 33) T39971_node_15 (SEQ ID NO: 34) T39971_node_16 (SEQ ID NO: 35) T39971_node_17 (SEQ ID NO: 36) T39971_node_26 (SEQ ID NO: 37) T39971_node_27 (SEQ ID NO: 38) T39971_node_28 (SEQ ID NO: 39) T39971_node_29 (SEQ ID NO: 40) T39971_node_3 (SEQ ID NO: 41) T39971_node_30 (SEQ ID NO: 42) T39971_node_34 (SEQ ID NO: 43) T39971_node_35 (SEQ ID NO: 44) T39971_node_36 (SEQ ID NO: 45) T39971_node_4 (SEQ ID NO: 46) T39971_node_5 (SEQ ID NO: 47) T39971_node_8 (SEQ ID NO: 48) T39971_node_9 (SEQ ID NO: 49)

[0082] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below: TABLE-US-00009 Protein Name T39971_P6 (SEQ ID NO: 51) T39971_P9 (SEQ ID NO: 52) T39971_P11 (SEQ ID NO: 53) T39971_P12 (SEQ ID NO: 54)

[0083] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00010 Transcript Name Z21368_PEA_1_T10 (SEQ ID NO: 55) Z21368_PEA_1_T11 (SEQ ID NO: 56) Z21368_PEA_1_T23 (SEQ ID NO: 57) Z21368_PEA_1_T24 (SEQ ID NO: 58) Z21368_PEA_1_T5 (SEQ ID NO: 59) Z21368_PEA_1_T6 (SEQ ID NO: 60) Z21368_PEA_1_T9 (SEQ ID NO: 61)

[0084] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00011 Segment Name Z21368_PEA_1_node_0 (SEQ ID NO: 62) Z21368_PEA_1_node_15 (SEQ ID NO: 63) Z21368_PEA_1_node_19 (SEQ ID NO: 64) Z21368_PEA_1_node_2 (SEQ ID NO: 65) Z21368_PEA_1_node_21 (SEQ ID NO: 66) Z21368_PEA_1_node_33 (SEQ ID NO: 67) Z21368_PEA_1_node_36 (SEQ ID NO: 68) Z21368_PEA_1_node_37 (SEQ ID NO: 69) Z21368_PEA_1_node_39 (SEQ ID NO: 70) Z21368_PEA_1_node_4 (SEQ ID NO: 71) Z21368_PEA_1_node_41 (SEQ ID NO: 72) Z21368_PEA_1_node_43 (SEQ ID NO: 73) Z21368_PEA_1_node_45 (SEQ ID NO: 74) Z21368_PEA_1_node_53 (SEQ ID NO: 75) Z21368_PEA_1_node_56 (SEQ ID NO: 76) Z21368_PEA_1_node_58 (SEQ ID NO: 77) Z21368_PEA_1_node_66 (SEQ ID NO: 78) Z21368_PEA_1_node_67 (SEQ ID NO: 79) Z21368_PEA_1_node_69 (SEQ ID NO: 80) Z21368_PEA_1_node_11 (SEQ ID NO: 81) Z21368_PEA_1_node_12 (SEQ ID NO: 82) Z21368_PEA_1_node_16 (SEQ ID NO: 83) Z21368_PEA_1_node_17 (SEQ ID NO: 84) Z21368_PEA_1_node_23 (SEQ ID NO: 85) Z21368_PEA_1_node_24 (SEQ ID NO: 86) Z21368_PEA_1_node_30 (SEQ ID NO: 87) Z21368_PEA_1_node_31 (SEQ ID NO: 88) Z21368_PEA_1_node_38 (SEQ ID NO: 89) Z21368_PEA_1_node_47 (SEQ ID NO: 90) Z21368_PEA_1_node_49 (SEQ ID NO: 91) Z21368_PEA_1_node_51 (SEQ ID NO: 92) Z21368_PEA_1_node_61 (SEQ ID NO: 93) Z21368_PEA_1_node_68 (SEQ ID NO: 94) Z21368_PEA_1_node_7 (SEQ ID NO: 95)

[0085] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00012 Protein Name Z21368_PEA_1_P2 (SEQ ID NO: 97) Z21368_PEA_1_P5 (SEQ ID NO: 98) Z21368_PEA_1_P15 (SEQ ID NO: 99) Z21368_PEA_1_P16 (SEQ ID NO: 100) Z21368_PEA_1_P22 (SEQ ID NO: 101) Z21368_PEA_1_P23 (SEQ ID NO: 102)

[0086] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00013 Transcript Name T59832_T11 (SEQ ID NO: 103) T59832_T15 (SEQ ID NO: 104) T59832_T22 (SEQ ID NO: 105) T59832_T28 (SEQ ID NO: 106) T59832_T6 (SEQ ID NO: 107) T59832_T8 (SEQ ID NO: 108)

[0087] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00014 Segment Name T59832_node_1 (SEQ ID NO: 109) T59832_node_22 (SEQ ID NO: 110) T59832_node_23 (SEQ ID NO: 111) T59832_node_24 (SEQ ID NO: 112) T59832_node_29 (SEQ ID NO: 113) T59832_node_39 (SEQ ID NO: 114) T59832_node_7 (SEQ ID NO: 115) T59832_node_10 (SEQ ID NO: 116) T59832_node_11 (SEQ ID NO: 117) T59832_node_12 (SEQ ID NO: 118) T59832_node_14 (SEQ ID NO: 119) T59832_node_16 (SEQ ID NO: 120) T59832_node_19 (SEQ ID NO: 121) T59832_node_2 (SEQ ID NO: 122) T59832_node_20 (SEQ ID NO: 123) T59832_node_25 (SEQ ID NO: 124) T59832_node_26 (SEQ ID NO: 125) T59832_node_27 (SEQ ID NO: 126) T59832_node_28 (SEQ ID NO: 127) T59832_node_3 (SEQ ID NO: 128) T59832_node_30 (SEQ ID NO: 129) T59832_node_31 (SEQ ID NO: 130) T59832_node_32 (SEQ ID NO: 131) T59832_node_34 (SEQ ID NO: 132) T59832_node_35 (SEQ ID NO: 133) T59832_node_36 (SEQ ID NO: 134) T59832_node_37 (SEQ ID NO: 135) T59832_node_38 (SEQ ID NO: 136) T59832_node_4 (SEQ ID NO: 137) T59832_node_5 (SEQ ID NO: 138) T59832_node_6 (SEQ ID NO: 139) T59832_node_8 (SEQ ID NO: 140) T59832_node_9 (SEQ ID NO: 141)

[0088] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00015 Protein Name T59832_P5 (SEQ ID NO: 143) T59832_P7 (SEQ ID NO: 144) T59832_P9 (SEQ ID NO: 145) T59832_P12 (SEQ ID NO: 146) T59832_P18 (SEQ ID NO: 147)

[0089] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00016 Transcript Name Z41644_PEA_1_T5 (SEQ ID NO: 208)

[0090] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00017 Segment Name Z41644_PEA_1_node_0 (SEQ ID NO: 209) Z41644_PEA_1_node_11 (SEQ ID NO: 210) Z41644_PEA_1_node_12 (SEQ ID NO: 211) Z41644_PEA_1_node_15 (SEQ ID NO: 212) Z41644_PEA_1_node_20 (SEQ ID NO: 213) Z41644_PEA_1_node_24 (SEQ ID NO: 214) Z41644_PEA_1_node_1 (SEQ ID NO: 215) Z41644_PEA_1_node_10 (SEQ ID NO: 216) Z41644_PEA_1_node_13 (SEQ ID NO: 217) Z41644_PEA_1_node_16 (SEQ ID NO: 218) Z41644_PEA_1_node_17 (SEQ ID NO: 219) Z41644_PEA_1_node_19 (SEQ ID NO: 220) Z41644_PEA_1_node_2 (SEQ ID NO: 221) Z41644_PEA_1_node_21 (SEQ ID NO: 222) Z41644_PEA_1_node_22 (SEQ ID NO: 223) Z41644_PEA_1_node_23 (SEQ ID NO: 224) Z41644_PEA_1_node_25 (SEQ ID NO: 225) Z41644_PEA_1_node_3 (SEQ ID NO: 226) Z41644_PEA_1_node_4 (SEQ ID NO: 227) Z41644_PEA_1_node_6 (SEQ ID NO: 228) Z41644_PEA_1_node_9 (SEQ ID NO: 229)

[0091] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00018 Protein Name Z41644_PEA_1_P10 (SEQ ID NO: 231)

[0092] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00019 Transcript Name HUMGRP5E_T4 (SEQ ID NO:148) HUMGRP5E_T5 (SEQ ID NO:149)

[0093] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00020 Segment Name HUMGRP5E_node_0 (SEQ ID NO:150) HUMGRP5E_node_2 (SEQ ID NO:151) HUMGRP5E_node_8 (SEQ ID NO:152) HUMGRP5E_node_3 (SEQ ID NO:153) HUMGRP5E_node_7 (SEQ ID NO:154)

[0094] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00021 Protein Name HUMGRP5E_P4 (SEQ ID NO:156) HUMGRP5E_P5 (SEQ ID NO:157)

[0095] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00022 Transcript Name AA155578_PEA_1_T10 (SEQ ID NO: 158) AA155578_PEA_1_T12 (SEQ ID NO: 159) AA155578_PEA_1_T13 (SEQ ID NO: 160) AA155578_PEA_1_T8 (SEQ ID NO: 161)

[0096] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00023 Segment Name AA155578_PEA_1_node_11 (SEQ ID NO: 162) AA155578_PEA_1_node_12 (SEQ ID NO: 163) AA155578_PEA_1_node_14 (SEQ ID NO: 164) AA155578_PEA_1_node_19 (SEQ ID NO: 165) AA155578_PEA_1_node_21 (SEQ ID NO: 166) AA155578_PEA_1_node_23 (SEQ ID NO: 167) AA155578_PEA_1_node_24 (SEQ ID NO: 168) AA155578_PEA_1_node_25 (SEQ ID NO: 169) AA155578_PEA_1_node_4 (SEQ ID NO: 170) AA155578_PEA_1_node_7 (SEQ ID NO: 171) AA155578_PEA_1_node_15 (SEQ ID NO: 172) AA155578_PEA_1_node_18 (SEQ ID NO: 173) AA155578_PEA_1_node_22 (SEQ ID NO: 174) AA155578_PEA_1_node_6 (SEQ ID NO: 175) AA155578_PEA_1_node_8 (SEQ ID NO: 176)

[0097] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00024 Protein Name AA155578_PEA_1_P4 (SEQ ID NO: 178) AA155578_PEA_1_P6 (SEQ ID NO: 179) AA155578_PEA_1_P8 (SEQ ID NO: 180) AA155578_PEA_1_P9 (SEQ ID NO: 181)

[0098] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00025 Transcript Name HSENA78_T5 (SEQ ID NO:182)

[0099] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00026 Segment Name HSENA78_node_0 (SEQ ID NO:183) HSENA78_node_2 (SEQ ID NO:184) HSENA78_node_6 (SEQ ID NO:185) HSENA78_node_9 (SEQ ID NO:186) HSENA78_node_3 (SEQ ID NO:187) HSENA78_node_4 (SEQ ID NO:188) HSENA78_node_8 (SEQ ID NO:189)

[0100] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below: TABLE-US-00027 Protein Name HSENA78_P2 (SEQ ID NO:191)

[0101] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00028 Transcript Name T94936_PEA_1_T1 (SEQ ID NO: 192) T94936_PEA_1_T2 (SEQ ID NO: 193)

[0102] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00029 Segment Name T94936_PEA_1_node_14 (SEQ ID NO: 194) T94936_PEA_1_node_16 (SEQ ID NO: 195) T94936_PEA_1_node_2 (SEQ ID NO: 196) T94936_PEA_1_node_20 (SEQ ID NO: 197) T94936_PEA_1_node_23 (SEQ ID NO: 198) T94936_PEA_1_node_0 (SEQ ID NO: 199) T94936_PEA_1_node_11 (SEQ ID NO: 200) T94936_PEA_1_node_13 (SEQ ID NO: 201) T94936_PEA_1_node_17 (SEQ ID NO: 202) T94936_PEA_1_node_6 (SEQ ID NO: 203) T94936_PEA_1_node_8 (SEQ ID NO: 204) T94936_PEA_1_node_9 (SEQ ID NO: 205)

[0103] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00030 Protein Name T94936_PEA_1_P2 (SEQ ID NO: 206) T94936_PEA_1_P3 (SEQ ID NO: 207)

[0104] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00031 Transcript Name M85491_PEA_1_T16 (SEQ ID NO: 232) M85491_PEA_1_T20 (SEQ ID NO: 233)

[0105] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00032 Segment Name M85491_PEA_1_node_0 (SEQ ID NO: 234) M85491_PEA_1_node_13 (SEQ ID NO: 235) M85491_PEA_1_node_21 (SEQ ID NO: 236) M85491_PEA_1_node_23 (SEQ ID NO: 237) M85491_PEA_1_node_24 (SEQ ID NO: 238) M85491_PEA_1_node_8 (SEQ ID NO: 239) M85491_PEA_1_node_9 (SEQ ID NO: 240) M85491_PEA_1_node_10 (SEQ ID NO: 241) M85491_PEA_1_node_18 (SEQ ID NO: 242) M85491_PEA_1_node_19 (SEQ ID NO: 243) M85491_PEA_1_node_6 (SEQ ID NO: 244)

[0106] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00033 Protein Name M85491_PEA_1_P13 (SEQ ID NO: 246) M85491_PEA_1_P14 (SEQ ID NO: 247)

[0107] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00034 Transcript Name HSSTROL3_T5 (SEQ ID NO:248) HSSTROL3_T8 (SEQ ID NO:249) HSSTROL3_T9 (SEQ ID NO:250) HSSTROL3_T10 (SEQ ID NO:251) HSSTROL3_T11 (SEQ ID NO:252) HSSTROL3_T12 (SEQ ID NO:253)

[0108] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00035 Segment Name HSSTROL3_node_6 (SEQ ID NO:254) HSSTROL3_node_10 (SEQ ID NO:255) HSSTROL3_node_13 (SEQ ID NO:256) HSSTROL3_node_15 (SEQ ID NO:257) HSSTROL3_node_19 (SEQ ID NO:258) HSSTROL3_node_21 (SEQ ID NO:259) HSSTROL3_node_24 (SEQ ID NO:260) HSSTROL3_node_25 (SEQ ID NO:261) HSSTROL3_node_26 (SEQ ID NO:262) HSSTROL3_node_28 (SEQ ID NO:263) HSSTROL3_node_29 (SEQ ID NO:264) HSSTROL3_node_11 (SEQ ID NO:265) HSSTROL3_node_17 (SEQ ID NO:266) HSSTROL3_node_18 (SEQ ID NO:267) HSSTROL3_node_20 (SEQ ID NO:268) HSSTROL3_node_27 (SEQ ID NO:269)

[0109] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00036 Protein Name HSSTROL3_P4 (SEQ ID NO:271) HSSTROL3_P5 (SEQ ID NO:272) HSSTROL3_P7 (SEQ ID NO:273) HSSTROL3_P8 (SEQ ID NO:274) HSSTROL3_P9 (SEQ ID NO:275)

[0110] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00037 Transcript Name AY180924_PEA_1_T1 (SEQ ID NO: 276)

[0111] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00038 Segment Name AY180924_PEA_1_node_3 (SEQ ID NO: 277) AY180924_PEA_1_node_0 (SEQ ID NO: 278) AY180924_PEA_1_node_2 (SEQ ID NO: 279)

[0112] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00039 Protein Name AY180924_PEA_1_P3 (SEQ ID NO: 281)

[0113] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00040 Transcript Name R75793_PEA_1_T1 (SEQ ID NO: 282) R75793_PEA_1_T3 (SEQ ID NO: 283) R75793_PEA_1_T5 (SEQ ID NO: 284)

[0114] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00041 R75793_PEA_1_node_0 (SEQ ID NO: 285) R75793_PEA_1_node_9 (SEQ ID NO: 286) R75793_PEA_1_node_11 (SEQ ID NO: 287) R75793_PEA_1_node_14 (SEQ ID NO: 288) R75793_PEA_1_node_4 (SEQ ID NO: 289) R75793_PEA_1_node_5 (SEQ ID NO: 290) R75793_PEA_1_node_6 (SEQ ID NO: 291) R75793_PEA_1_node_8 (SEQ ID NO: 292) R75793_PEA_1_node_13 (SEQ ID NO: 293)

[0115] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00042 Protein Name R75793_PEA_1_P2 (SEQ ID NO: 295) R75793_PEA_1_P5 (SEQ ID NO: 296) R75793_PEA_1_P6 (SEQ ID NO: 297)

[0116] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00043 Transcript Name HUMCA1XIA_T16 (SEQ ID NO:298) HUMCA1XIA_T17 (SEQ ID NO:299) HUMCA1XIA_T19 (SEQ ID NO:300) HUMCA1XIA_T20 (SEQ ID NO:301)

[0117] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00044 Segment Name HUMCA1XIA_node_0 (SEQ ID NO:302) HUMCA1XIA_node_2 (SEQ ID NO:303) HUMCA1XIA_node_4 (SEQ ID NO:304) HUMCA1XIA_node_6 (SEQ ID NO:305) HUMCA1XIA_node_8 (SEQ ID NO:306) HUMCA1XIA_node_9 (SEQ ID NO:307) HUMCA1XIA_node_18 (SEQ ID NO:308) HUMCA1XIA_node_54 (SEQ ID NO:309) HUMCA1XIA_node_55 (SEQ ID NO:310) HUMCA1XIA_node_92 (SEQ ID NO:311) HUMCA1XIA_node_11 (SEQ ID NO:312) HUMCA1XIA_node_15 (SEQ ID NO:313) HUMCA1XIA_node_19 (SEQ ID NO:314) HUMCA1XIA_node_21 (SEQ ID NO:315) HUMCA1XIA_node_23 (SEQ ID NO:316) HUMCA1XIA_node_25 (SEQ ID NO:317) HUMCA1XIA_node_27 (SEQ ID NO:318) HUMCA1XIA_node_29 (SEQ ID NO:319) HUMCA1XIA_node_31 (SEQ ID NO:320) HUMCA1XIA_node_33 (SEQ ID NO:321) HUMCA1XIA_node_35 (SEQ ID NO:322) HUMCA1XIA_node_37 (SEQ ID NO:323) HUMCA1XIA_node_39 (SEQ ID NO:324) HUMCA1XIA_node_41 (SEQ ID NO:325) HUMCA1XIA_node_43 (SEQ ID NO:326) HUMCA1XIA_node_45 (SEQ ID NO:327) HUMCA1XIA_node_47 (SEQ ID NO:328) HUMCA1XIA_node_49 (SEQ ID NO:329) HUMCA1XIA_node_51 (SEQ ID NO:330) HUMCA1XIA_node_57 (SEQ ID NO:331) HUMCA1XIA_node_59 (SEQ ID NO:332) HUMCA1XIA_node_62 (SEQ ID NO:333) HUMCA1XIA_node_64 (SEQ ID NO:334) HUMCA1XIA_node_66 (SEQ ID NO:335) HUMCA1XIA_node_68 (SEQ ID NO:336) HUMCA1XIA_node_70 (SEQ ID NO:337) HUMCA1XIA_node_72 (SEQ ID NO:338) HUMCA1XIA_node_74 (SEQ ID NO:339) HUMCA1XIA_node_76 (SEQ ID NO:340) HUMCA1XIA_node_78 (SEQ ID NO:341) HUMCA1XIA_node_81 (SEQ ID NO:342) HUMCA1XIA_node_83 (SEQ ID NO:343) HUMCA1XIA_node_85 (SEQ ID NO:344) HUMCA1XIA_node_87 (SEQ ID NO:345) HUMCA1XIA_node_89 (SEQ ID NO:346) HUMCA1XIA_node_91 (SEQ ID NO:347)

[0118] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00045 Protein Name HUMCA1XIA_P14 (SEQ ID NO:350) HUMCA1XIA_P15 (SEQ ID NO:351) HUMCA1XIA_P16 (SEQ ID NO:352) HUMCA1XIA_P17 (SEQ ID NO:353)

[0119] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00046 Transcript Name R20779_T7 (SEQ ID NO: 354)

[0120] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00047 Segment Name R20779_node_0 (SEQ ID NO: 355) R20779_node_2 (SEQ ID NO: 356) R20779_node_7 (SEQ ID NO: 357) R20779_node_9 (SEQ ID NO: 358) R20779_node_18 (SEQ ID NO: 359) R20779_node_21 (SEQ ID NO: 360) R20779_node_24 (SEQ ID NO: 361) R20779_node_27 (SEQ ID NO: 362) R20779_node_28 (SEQ ID NO: 363) R20779_node_30 (SEQ ID NO: 364) R20779_node_31 (SEQ ID NO: 365) R20779_node_32 (SEQ ID NO: 366) R20779_node_1 (SEQ ID NO: 367) R20779_node_3 (SEQ ID NO: 368) R20779_node_10 (SEQ ID NO: 369) R20779_node_11 (SEQ ID NO: 370) R20779_node_14 (SEQ ID NO: 371) R20779_node_17 (SEQ ID NO: 372) R20779_node_19 (SEQ ID NO: 373) R20779_node_20 (SEQ ID NO: 374) R20779_node_22 (SEQ ID NO: 375) R20779_node_23 (SEQ ID NO: 376) R20779_node_25 (SEQ ID NO: 377) R20779_node_29 (SEQ ID NO: 378)

[0121] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence according to R20779_P2 (SEQ ID NO:380).

[0122] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00048 Transcript Name HSS100PCB_T1 (SEQ ID NO:381)

[0123] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00049 Segment Name HSS100PCB_node_3 (SEQ ID NO:382) HSS100PCB_node_4 (SEQ ID NO:383) HSS100PCB_node_5 (SEQ ID NO:384)

[0124] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence according to HSS100PCB_P3 (SEQ ID NO:386).

[0125] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00050 Transcript Name HSCOC4_PEA_1_T1 (SEQ ID NO:387) HSCOC4_PEA_1_T2 (SEQ ID NO:388) HSCOC4_PEA_1_T3 (SEQ ID NO:389) HSCOC4_PEA_1_T4 (SEQ ID NO:390) HSCOC4_PEA_1_T5 (SEQ ID NO:391) HSCOC4_PEA_1_T7 (SEQ ID NO:392) HSCOC4_PEA_1_T8 (SEQ ID NO:393) HSCOC4_PEA_1_T11 (SEQ ID NO:394) HSCOC4_PEA_1_T12 (SEQ ID NO:395) HSCOC4_PEA_1_T14 (SEQ ID NO:396) HSCOC4_PEA_1_T15 (SEQ ID NO:397) HSCOC4_PEA_1_T20 (SEQ ID NO:398) HSCOC4_PEA_1_T21 (SEQ ID NO:399) HSCOC4_PEA_1_T25 (SEQ ID NO:400) HSCOC4_PEA_1_T28 (SEQ ID NO:401) HSCOC4_PEA_1_T30 (SEQ ID NO:402) HSCOC4_PEA_1_T31 (SEQ ID NO:403) HSCOC4_PEA_1_T32 (SEQ ID NO:404) HSCOC4_PEA_1_T40 (SEQ ID NO:405)

[0126] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00051 Segment Name HSCOC4_PEA_1_node_1 (SEQ ID NO:406) HSCOC4_PEA_1_node_5 (SEQ ID NO:407) HSCOC4_PEA_1_node_7 (SEQ ID NO:408) HSCOC4_PEA_1_node_30 (SEQ ID NO:409) HSCOC4_PEA_1_node_33 (SEQ ID NO:410) HSCOC4_PEA_1_node_35 (SEQ ID NO:411) HSCOC4_PEA_1_node_37 (SEQ ID NO:412) HSCOC4_PEA_1_node_39 (SEQ ID NO:413) HSCOC4_PEA_1_node_43 (SEQ ID NO:414) HSCOC4_PEA_1_node_48 (SEQ ID NO:415) HSCOC4_PEA_1_node_49 (SEQ ID NO:416) HSCOC4_PEA_1_node_51 (SEQ ID NO:417) HSCOC4_PEA_1_node_58 (SEQ ID NO:418) HSCOC4_PEA_1_node_59 (SEQ ID NO:419) HSCOC4_PEA_1_node_62 (SEQ ID NO:420) HSCOC4_PEA_1_node_66 (SEQ ID NO:421) HSCOC4_PEA_1_node_72 (SEQ ID NO:422) HSCOC4_PEA_1_node_77 (SEQ ID NO:423) HSCOC4_PEA_1_node_79 (SEQ ID NO:424) HSCOC4_PEA_1_node_93 (SEQ ID NO:425) HSCOC4_PEA_1_node_100 (SEQ ID NO:426) HSCOC4_PEA_1_node_105 (SEQ ID NO:427) HSCOC4_PEA_1_node_107 (SEQ ID NO:428) HSCOC4_PEA_1_node_108 (SEQ ID NO:429) HSCOC4_PEA_1_node_109 (SEQ ID NO:430) HSCOC4_PEA_1_node_110 (SEQ ID NO:431) HSCOC4_PEA_1_node_112 (SEQ ID NO:432) HSCOC4_PEA_1_node_113 (SEQ ID NO:433) HSCOC4_PEA_1_node_2 (SEQ ID NO:434) HSCOC4_PEA_1_node_8 (SEQ ID NO:435) HSCOC4_PEA_1_node_10 (SEQ ID NO:436) HSCOC4_PEA_1_node_12 (SEQ ID NO:437) HSCOC4_PEA_1_node_14 (SEQ ID NO:438) HSCOC4_PEA_1_node_17 (SEQ ID NO:439) HSCOC4_PEA_1_node_19 (SEQ ID NO:440) HSCOC4_PEA_1_node_21 (SEQ ID NO:441) HSCOC4_PEA_1_node_22 (SEQ ID NO:442) HSCOC4_PEA_1_node_28 (SEQ ID NO:443) HSCOC4_PEA_1_node_29 (SEQ ID NO:444) HSCOC4_PEA_1_node_41 (SEQ ID NO:445) HSCOC4_PEA_1_node_45 (SEQ ID NO:446) HSCOC4_PEA_1_node_47 (SEQ ID NO:447) HSCOC4_PEA_1_node_50 (SEQ ID NO:448) HSCOC4_PEA_1_node_53 (SEQ ID NO:449) HSCQC4_PEA_1_node_55 (SEQ ID NO:450) HSCOC4_PEA_1_node_57 (SEQ ID NO:451) HSCOC4_PEA_1_node_60 (SEQ ID NO:452) HSCOC4_PEA_1_node_64 (SEQ ID NO:453) HSCOC4_PEA_1_node_69 (SEQ ID NO:454) HSCOC4_PEA_1_node_70 (SEQ ID NO:455) HSCOC4_PEA_1_node_71 (SEQ ID NO:456) HSCOC4_PEA_1_node_73 (SEQ ID NO:457) HSCOC4_PEA_1_node_74 (SEQ ID NO:458) HSCOC4_PEA_1_node_75 (SEQ ID NO:459) HSCOC4_PEA_1_node_76 (SEQ ID NO:460) HSCOC4_PEA_1_node_78 (SEQ ID NO:461) HSCOC4_PEA_1_node_80 (SEQ ID NO:462) RSCOC4_PEA_1_node_82 (SEQ ID NO:463) HSCOC4_PEA_1_node_83 (SEQ ID NO:464) HSCOC4_PEA_1_node_84 (SEQ ID NO:465) HSCOC4_PEA_1_node_85 (SEQ ID NO:466) HSCOC4_PEA_1_node_86 (SEQ ID NO:467) HSCOC4_PEA_1_node_87 (SEQ ID NO:468) HSCOC4_PEA_1_node_88 (SEQ ID NO:469) HSCOC4_PEA_1_node_89 (SEQ ID NO:470) HSCOC4_PEA_1_node_90 (SEQ ID NO:471) HSCOC4_PEA_1_node_91 (SEQ ID NO:472) HSCOC4_PEA_1_node_92 (SEQ ID NO:473) HSCOC4_PEA_1_node_94 (SEQ ID NO:474) HSCOC4_PEA_1_node_96 (SEQ ID NO:475) HSCOC4_PEA_1_node_97 (SEQ ID NO:476) HSCOC4_PEA_1_node_98 (SEQ ID NO:477) HSCOC4_PEA_1_node_99 (SEQ ID NO:478) HSCOC4_PEA_1_node_101 (SEQ ID NO:479) HSCOC4_PEA_1_node_102 (SEQ ID NO:480) HSCOC4_PEA_1_node_103 (SEQ ID NO:481) HSCOC4_PEA_1_node_104 (SEQ ID NO:482) HSCOC4_PEA_1_node_106 (SEQ ID NO:483) HSCOC4_PEA_1_node_111 (SEQ ID NO:484)

[0127] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00052 Protein Name HSCOC4_PEA_1_P3 (SEQ ID NO:488) HSCOC4_PEA_1_P5 (SEQ ID NO:489) HSCOC4_PEA_1_P6 (SEQ ID NO:490) HSCOC4_PEA_1_P12 (SEQ ID NO:491) HSCOC4_PEA_1_P15 (SEQ ID NO:492) HSCOC4_PEA_1_P16 (SEQ ID NO:493) HSCOC4_PEA_1_P20 (SEQ ID NO:494) HSCOC4_PEA_1_P9 (SEQ ID NO:495) HSCOC4_PEA_1_P22 (SEQ ID NO:496) HSCOC4_PEA_1_P23 (SEQ ID NO:497) HSCOC4_PEA_1_P24 (SEQ ID NO:498) HSCOC4_PEA_1_P25 (SEQ ID NO:499) HSCOC4_PEA_1_P26 (SEQ ID NO:500) HSCOC4_PEA_1_P30 (SEQ ID NO:501) HSCOC4_PEA_1_P38 (SEQ ID NO:502) HSCOC4_PEA_1_P39 (SEQ ID NO:503) HSCOC4_PEA_1_P40 (SEQ ID NO:504) HSCOC4_PEA_1_P41 (SEQ ID NO:505) HSCOC4_PEA_1_P42 (SEQ ID NO:506)

[0128] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00053 Transcript Name HUMTREFAC_PEA_2_T4 (SEQ ID NO:507) HUMTREFAC_PEA_2_T5 (SEQ ID NO:508)

[0129] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00054 Segment Name HUMTREFAC_PEA_2_node_0 (SEQ ID NO:509) HUMTREFAC_PEA_2_node_9 (SEQ ID NO:510) HUMTREFAC_PEA_2_node_2 (SEQ ID NO:511) HUMTREFAC_PEA_2_node_3 (SEQ ID NO:512) HUMTREFAC_PEA_2_node_4 (SEQ ID NO:513) HUMTREFAC_PEA_2_node_5 (SEQ ID NO:514) HUMTREFAC_PEA_2_node_8 (SEQ ID NO:515)

[0130] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00055 Protein Name HUMTREFAC_PEA_2_P7 (SEQ ID NO:517) HUMTREFAC_PEA_2_P8 (SEQ ID NO:518)

[0131] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00056 Transcript Name HUMOSTRO_PEA_1_PEA_1_T14 (SEQ ID NO:519) HUMOSTRO_PEA_1_PEA_1_T16 (SEQ ID NO:520) HUMOSTRO_PEA_1_PEA_1_T30 (SEQ ID NO:521)

[0132] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00057 Segment Name HUMOSTRO_PEA_1_PEA_1_node_0 (SEQ ID NO:522) HUMOSTRO_PEA_1_PEA_1_node_10 (SEQ ID NO:523) HUMOSTRO_PEA_1_PEA_1_node_16 (SEQ ID NO:524) HUMOSTRO_PEA_1_PEA_1_node_23 (SEQ ID NO:525) HUMOSTRO_PEA_1_PEA_1_node_31 (SEQ ID NO:526) HUMOSTRO_PEA_1_PEA_1_node_43 (SEQ ID NO:527) HUMOSTRO_PEA_1_PEA_1_node_3 (SEQ ID NO:528) HUMOSTRO_PEA_1_PEA_1_node_5 (SEQ ID NO:529) HUMOSTRO_PEA_1_PEA_1_node_7 (SEQ ID NO:530) HUMOSTRO_PEA_1_PEA_1_node_8 (SEQ ID NO:531) HUMOSTRO_PEA_1_PEA_1_node_15 (SEQ ID NO:532) HUMOSTRO_PEA_1_PEA_1_node_17 (SEQ ID NO:533) HUMOSTRO_PEA_1_PEA_1_node_20 (SEQ ID NO:534) HUMOSTRO_PEA_1_PEA_1_node_21 (SEQ ID NO:535) HUMOSTRO_PEA_1_PEA_1_node_22 (SEQ ID NO:536) HUMOSTRO_PEA_1_PEA_1_node_24 (SEQ ID NO:537) HUMOSTRO_PEA_1_PEA_1_node_26 (SEQ ID NO:538) HUMOSTRO_PEA_1_PEA_1_node_27 (SEQ ID NO:539) HUMOSTRO_PEA_1_PEA_1_node_28 (SEQ ID NO:540) HUMOSTRO_PEA_1_PEA_1_node_29 (SEQ ID NO:541) HUMOSTRO_PEA_1_PEA_1_node_30 (SEQ ID NO:542) HUMOSTRO_PEA_1_PEA_1_node_32 (SEQ ID NO:543) HUMOSTRO_PEA_1_PEA_1_node_34 (SEQ ID NO:544) HUMOSTRO_PEA_1_PEA_1_node_36 (SEQ ID NO:545) HUMOSTRO_PEA_1_PEA_1_node_37 (SEQ ID NO:546) HUMOSTRO_PEA_1_PEA_1_node_38 (SEQ ID NO:547) HUMOSTRO_PEA_1_PEA_1_node_39 (SEQ ID NO:548) HUMOSTRO_PEA_1_PEA_1_node_40 (SEQ ID NO:549) HUMOSTRO_PEA_1_PEA_1_node_41 (SEQ ID NO:550) HUMOSTRO_PEA_1_PEA_1_node_42 (SEQ ID NO:551)

[0133] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00058 Protein Name HUMOSTRO_PEA_1_PEA_1_P21 (SEQ ID NO:553) HUMOSTRO_PEA_1_PEA_1_P25 (SEQ ID NO:554) HUMOSTRO_PEA_1_PEA_1_P30 (SEQ ID NO:555)

[0134] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a polynucleotide having a sequence selected from the group consisting of: R11723_PEA.sub.--1_T15 (SEQ ID NO:556), R11723_PEA.sub.--1_T17 (SEQ ID NO:557), R11723_PEA.sub.--1_T19 (SEQ ID NO:558), R11723_PEA.sub.--1_T20 (SEQ ID NO:559), R11723_PEA.sub.--1_T5 (SEQ ID NO:560), or R11723_PEA.sub.--1_T6 (SEQ ID NO:561).

[0135] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a node having a sequence selected from the group consisting of: R11723_PEA.sub.--1_node.sub.--13 (SEQ ID NO:562), R11723_PEA.sub.--1_node.sub.--16 (SEQ ID NO:563), R11723_PEA.sub.--1_node.sub.--19 (SEQ ID NO:564), R11723_PEA.sub.--1_node.sub.--2 (SEQ ID NO:565), R11723_PEA.sub.--1_node.sub.--22 (SEQ ID NO:566), R11723_PEA.sub.--1_node.sub.--31 (SEQ ID NO:567), R11723_PEA.sub.--1_node.sub.--10 (SEQ ID NO:568), R11723_PEA.sub.--1_node.sub.--11 (SEQ ID NO:569), R11723_PEA.sub.--1_node.sub.--15 (SEQ ID NO:570), R11723_PEA.sub.--1_node.sub.--18 (SEQ ID NO:571), R11723_PEA.sub.--1_node.sub.--20 (SEQ ID NO:572), R11723_PEA.sub.--1_node.sub.--21 (SEQ ID NO:573), R11723_PEA.sub.--1_node.sub.--23 (SEQ ID NO:574), R11723_PEA.sub.--1_node.sub.--24 (SEQ ID NO:575), R11723_PEA.sub.--1_node.sub.--25 (SEQ ID NO:576), R11723_PEA.sub.--1_node.sub.--26 (SEQ ID NO:577), R11723_PEA.sub.--1_node.sub.--27 (SEQ ID NO:578), R11723_PEA.sub.--1_node.sub.--28 (SEQ ID NO:579), R11723_PEA.sub.--1_node.sub.--29 (SEQ ID NO:580), R11723_PEA.sub.--1_node.sub.--3 (SEQ ID NO:581), R11723_PEA.sub.--1_node.sub.--30 (SEQ ID NO:582), R11723_PEA.sub.--1_node.sub.--4 (SEQ ID NO:583), R11723_PEA.sub.--1_node.sub.--5 (SEQ ID NO:584), R11723_PEA.sub.--1_node.sub.--6 (SEQ ID NO:585), R11723_PEA.sub.--1_node.sub.--7 (SEQ ID NO:586) or R11723_PEA.sub.--1_node.sub.--8 (SEQ ID NO:587).

[0136] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising a polypeptide having a sequence selected from the group consisting of: R11723_PEA.sub.--1.sub.13 P2 (SEQ ID NO:588), R11723_PEA.sub.--1_P6 (SEQ ID NO:589), R11723_PEA.sub.--1_P7 (SEQ ID NO:590), R11723_PEA.sub.--1_P13 (SEQ ID NO:591), or R11723_PEA.sub.--1_P10 (SEQ ID NO:592).

[0137] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00059 Transcript Name T46984_PEA_1_T2 (SEQ ID NO: 593) T46984_PEA_1_T3 (SEQ ID NO: 594) T46984_PEA_1_T12 (SEQ ID NO: 595) T46984_PEA_1_T13 (SEQ ID NO: 596) T46984_PEA_1_T14 (SEQ ID NO: 597) T46984_PEA_1_T15 (SEQ ID NO: 598) T46984_PEA_1_T19 (SEQ ID NO: 599) T46984_PEA_1_T23 (SEQ ID NO: 600) T46984_PEA_1_T27 (SEQ ID NO: 601) T46984_PEA_1_T32 (SEQ ID NO: 602) T46984_PEA_1_T34 (SEQ ID NO: 603) T46984_PEA_1_T35 (SEQ ID NO: 604) T46984_PEA_1_T40 (SEQ ID NO: 605) T46984_PEA_1_T42 (SEQ ID NO: 606) T46984_PEA_1_T43 (SEQ ID NO: 607) T46984_PEA_1_T46 (SEQ ID NO: 608) T46984_PEA_1_T47 (SEQ ID NO: 609) T46984_PEA_1_T48 (SEQ ID NO: 610) T46984_PEA_1_T51 (SEQ ID NO: 611) T46984_PEA_1_T52 (SEQ ID NO: 612) T46984_PEA_1_T54 (SEQ ID NO: 613)

[0138] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00060 Segment Name T46984_PEA_1_node_2 (SEQ ID NO: 614) T46984_PEA_1_node_4 (SEQ ID NO: 615) T46984_PEA_1_node_6 (SEQ ID NO: 616) T46984_PEA_1_node_12 (SEQ ID NO: 617) T46984_PEA_1_node_14 (SEQ ID NO: 618) T46984_PEA_1_node_25 (SEQ ID NO: 619) T46984_PEA_1_node_29 (SEQ ID NO: 620) T46984_PEA_1_node_34 (SEQ ID NO: 621) T46984_PEA_1_node_46 (SEQ ID NO: 622) T46984_PEA_1_node_47 (SEQ ID NO: 623) T46984_PEA_1_node_52 (SEQ ID NO: 624) T46984_PEA_1_node_65 (SEQ ID NO: 625) T46984_PEA_1_node_69 (SEQ ID NO: 626) T46984_PEA_1_node_75 (SEQ ID NO: 627) T46984_PEA_1_node_86 (SEQ ID NO: 628) T46984_PEA_1_node_9 (SEQ ID NO: 629) T46984_PEA_1_node_13 (SEQ ID NO: 630) T46984_PEA_1_node_19 (SEQ ID NO: 631) T46984_PEA_1_node_21 (SEQ ID NO: 632) T46984_PEA_1_node_22 (SEQ ID NO: 633) T46984_PEA_1_node_26 (SEQ ID NO: 634) T46984_PEA_1_node_28 (SEQ ID NO: 635) T46984_PEA_1_node_31 (SEQ ID NO: 636) T46984_PEA_1_node_32 (SEQ ID NO: 637) T46984_PEA_1_node_38 (SEQ ID NO: 638) T46984_PEA_1_node_39 (SEQ ID NO: 639) T46984_PEA_1_node_40 (SEQ ID NO: 640) T46984_PEA_1_node_42 (SEQ ID NO: 641) T46984_PEA_1_node_43 (SEQ ID NO: 642) T46984_PEA_1_node_48 (SEQ ID NO: 643) T46984_PEA_1_node_49 (SEQ ID NO: 644) T46984_PEA_1_node_50 (SEQ ID NO: 645) T46984_PEA_1_node_51 (SEQ ID NO: 646) T46984_PEA_1_node_53 (SEQ ID NO: 647) T46984_PEA_1_node_54 (SEQ ID NO: 648) T46984_PEA_1_node_55 (SEQ ID NO: 649) T46984_PEA_1_node_57 (SEQ ID NO: 650) T46984_PEA_1_node_60 (SEQ ID NO: 651) T46984_PEA_1_node_62 (SEQ ID NO: 652) T46984_PEA_1_node_66 (SEQ ID NO: 653) T46984_PEA_1_node_67 (SEQ ID NO: 654) T46984_PEA_1_node_70 (SEQ ID NO: 655) T46984_PEA_1_node_71 (SEQ ID NO: 656) T46984_PEA_1_node_72 (SEQ ID NO: 657) T46984_PEA_1_node_73 (SEQ ID NO: 658) T46984_PEA_1_node_74 (SEQ ID NO: 659) T46984_PEA_1_node_83 (SEQ ID NO: 660) T46984_PEA_1_node_84 (SEQ ID NO: 661) T46984_PEA_1_node_85 (SEQ ID NO: 662)

[0139] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00061 Protein Name T46984_PEA_1_P2 (SEQ ID NO: 664) T46984_PEA_1_P3 (SEQ ID NO: 665) T46984_PEA_1_P10 (SEQ ID NO: 666) T46984_PEA_1_P11 (SEQ ID NO: 667) T46984_PEA_1_P12 (SEQ ID NO: 668) T46984_PEA_1_P21 (SEQ ID NO: 669) T46984_PEA_1_P27 (SEQ ID NO: 670) T46984_PEA_1_P32 (SEQ ID NO: 671) T46984_PEA_1_P34 (SEQ ID NO: 672) T46984_PEA_1_P35 (SEQ ID NO: 673) T46984_PEA_1_P38 (SEQ ID NO: 674) T46984_PEA_1_P39 (SEQ ID NO: 675) T46984_PEA_1_P45 (SEQ ID NO: 676) T46984_PEA_1_P46 (SEQ ID NO: 677)

[0140] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00062 Transcript Name T11628_PEA_1_T3 (SEQ ID NO: 678) T11628_PEA_1_T4 (SEQ ID NO: 679) T11628_PEA_1_T5 (SEQ ID NO: 680) T11628_PEA_1_T7 (SEQ ID NO: 681) T11628_PEA_1_T9 (SEQ ID NO: 682) T11628_PEA_1_T11 (SEQ ID NO: 683)

[0141] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00063 Segment Name T11628_PEA_1_node_7 (SEQ ID NO: 684) T11628_PEA_1_node_11 (SEQ ID NO: 685) T11628_PEA_1_node_16 (SEQ ID NO: 686) T11628_PEA_1_node_22 (SEQ ID NO: 687) T11628_PEA_1_node_25 (SEQ ID NO: 688) T11628_PEA_1_node_31 (SEQ ID NO: 689) T11628_PEA_1_node_37 (SEQ ID NO: 690) T11628_PEA_1_node_0 (SEQ ID NO: 691) T11628_PEA_1_node_4 (SEQ ID NO: 692) T11628_PEA_1_node_9 (SEQ ID NO: 693) T11628_PEA_1_node_13 (SEQ ID NO: 694) T11628_PEA_1_node_14 (SEQ ID NO: 695) T11628_PEA_1_node_17 (SEQ ID NO: 696) T11628_PEA_1_node_18 (SEQ ID NO: 697) T11628_PEA_1_node_19 (SEQ ID NO: 698) T11628_PEA_1_node_24 (SEQ ID NO: 699) T11628_PEA_1_node_27 (SEQ ID NO: 700) T11628_PEA_1_node_28 (SEQ ID NO: 701) T11628_PEA_1_node_29 (SEQ ID NO: 702) T11628_PEA_1_node_30 (SEQ ID NO: 703) T11628_PEA_1_node_32 (SEQ ID NO: 704) T11628_PEA_1_node_33 (SEQ ID NO: 705) T11628_PEA_1_node_34 (SEQ ID NO: 706) T11628_PEA_1_node_35 (SEQ ID NO: 707) T11628_PEA_1_node_36 (SEQ ID NO: 708)

[0142] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00064 Protein Name T11628_PEA_1_P2 (SEQ ID NO: 712) T11628_PEA_1_P5 (SEQ ID NO: 713) T11628_PEA_1_P7 (SEQ ID NO: 714) T11628_PEA_1_P10 (SEQ ID NO: 715)

[0143] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00065 Transcript Name M78076_PEA_1_T2 (SEQ ID NO: 716) M78076_PEA_1_T3 (SEQ ID NO: 717) M78076_PEA_1_T5 (SEQ ID NO: 718) M78076_PEA_1_T13 (SEQ ID NO: 719) M78076_PEA_1_T15 (SEQ ID NO: 720) M78076_PEA_1_T23 (SEQ ID NO: 721) M78076_PEA_1_T26 (SEQ ID NO: 722) M78076_PEA_1_T27 (SEQ ID NO: 723) M78076_PEA_1_T28 (SEQ ID NO: 724)

[0144] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00066 Segment Name M78076_PEA_1_node_0 (SEQ ID NO: 725) M78076_PEA_1_node_10 (SEQ ID NO: 726) M78076_PEA_1_node_15 (SEQ ID NO: 727) M78076_PEA_1_node_18 (SEQ ID NO: 728) M78076_PEA_1_node_20 (SEQ ID NO: 729) M78076_PEA_1_node_24 (SEQ ID NO: 730) M78076_PEA_1_node_26 (SEQ ID NO: 731) M78076_PEA_1_node_29 (SEQ ID NO: 732) M78076_PEA_1_node_32 (SEQ ID NO: 733) M78076_PEA_1_node_35 (SEQ ID NO: 734) M78076_PEA_1_node_37 (SEQ ID NO: 735) M78076_PEA_1_node_46 (SEQ ID NO: 736) M78076_PEA_1_node_47 (SEQ ID NO: 737) M78076_PEA_1_node_54 (SEQ ID NO: 738) M78076_PEA_1_node_1 (SEQ ID NO: 739) M78076_PEA_1_node_2 (SEQ ID NO: 740) M78076_PEA_1_node_3 (SEQ ID NO: 741) M78076_PEA_1_node_6 (SEQ ID NO: 742) M78076_PEA_1_node_7 (SEQ ID NO: 743) M78076_PEA_1_node_12 (SEQ ID NO: 744) M78076_PEA_1_node_22 (SEQ ID NO: 745) M78076_PEA_1_node_27 (SEQ ID NO: 746) M78076_PEA_1_node_30 (SEQ ID NO: 747) M78076_PEA_1_node_31 (SEQ ID NO: 748) M78076_PEA_1_node_34 (SEQ ID NO: 749) M78076_PEA_1_node_36 (SEQ ID NO: 750) M78076_PEA_1_node_41 (SEQ ID NO: 751) M78076_PEA_1_node_42 (SEQ ID NO: 752) M78076_PEA_1_node_43 (SEQ ID NO: 753) M78076_PEA_1_node_45 (SEQ ID NO: 754) M78076_PEA_1_node_49 (SEQ ID NO: 755) M78076_PEA_1_node_50 (SEQ ID NO: 756) M78076_PEA_1_node_51 (SEQ ID NO: 757) M78076_PEA_1_node_52 (SEQ ID NO: 758) M78076_PEA_1_node_53 (SEQ ID NO: 759)

[0145] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00067 Protein Name M78076_PEA_1_P3 (SEQ ID NO: 761) M78076_PEA_1_P4 (SEQ ID NO: 762) M78076_PEA_1_P12 (SEQ ID NO: 763) M78076_PEA_1_P14 (SEQ ID NO: 764) M78076_PEA_1_P21 (SEQ ID NO: 765) M78076_PEA_1_P24 (SEQ ID NO: 766) M78076_PEA_1_P2 (SEQ ID NO: 767) M78076_PEA_1_P25 (SEQ ID NO: 768)

[0146] According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: TABLE-US-00068 Transcript Name HSMUC1A_PEA_1_T12 (SEQ ID NO:769) HSMUC1A_PEA_1_T26 (SEQ ID NO:770) HSMUC1A_PEA_1_T28 (SEQ ID NO:771) HSMUC1A_PEA_1_T29 (SEQ ID NO:772) HSMUC1A_PEA_1_T30 (SEQ ID NO:773) HSMUC1A_PEA_1_T31 (SEQ ID NO:774) HSMUC1A_PEA_1_T33 (SEQ ID NO:775) HSMUC1A_PEA_1_T34 (SEQ ID NO:776) HSMUC1A_PEA_1_T35 (SEQ ID NO:777) HSMUC1A_PEA_1_T36 (SEQ ID NO:778) HSMUC1A_PEA_1_T40 (SEQ ID NO:779) HSMUC1A_PEA_1_T42 (SEQ ID NO:780) HSMUC1A_PEA_1_T43 (SEQ ID NO:781) HSMUC1A_PEA_1_T47 (SEQ ID NO:782)

[0147] a nucleic acid sequence comprising a sequence in the table below: TABLE-US-00069 Segment Name HSMUC1A_PEA_1_node_0 (SEQ ID NO:783) HSMUC1A_PEA_1_node_14 (SEQ ID NO:784) HSMUC1A_PEA_1_node_24 (SEQ ID NO:785) HSMUC1A_PEA_1_node_29 (SEQ ID NO:786) HSMUC1A_PEA_1_node_35 (SEQ ID NO:787) HSMUC1A_PEA_1_node_38 (SEQ ID NO:788) HSMUC1A_PEA_1_node_3 (SEQ ID NO:789) HSMUC1A_PEA_1_node_4 (SEQ ID NO:790) HSMUC1A_PEA_1_node_5 (SEQ ID NO:791) HSMUC1A_PEA_1_node_6 (SEQ ID NO:792) HSMUC1A_PEA_1_node_7 (SEQ ID NO:793) HSMUC1A_PEA_1_node_17 (SEQ ID NO:794) HSMUC1A_PEA_1_node_18 (SEQ ID NO:795) HSMUC1A_PEA_1_node_20 (SEQ ID NO:796) HSMUC1A_PEA_1_node_21 (SEQ ID NO:797) HSMUC1A_PEA_1_node_23 (SEQ ID NO:798) HSMUC1A_PEA_1_node_26 (SEQ ID NO:799) HSMUC1A_PEA_1_node_27 (SEQ ID NO:800) HSMUC1A_PEA_1_node_31 (SEQ ID NO:801) HSMUC1A_PEA_1_node_34 (SEQ ID NO:802) HSMUC1A_PEA_1_node_36 (SEQ ID NO:803) HSMUC1A_PEA_1_node_37 (SEQ ID NO:804)

[0148] According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below TABLE-US-00070 Protein Name HSMUC1A_PEA_1_P25 (SEQ ID NO:806) HSMUC1A_PEA_1_P29 (SEQ ID NO:807) HSMUC1A_PEA_1_P30 (SEQ ID NO:808) HSMUC1A_PEA_1_P32 (SEQ ID NO:809) HSMUC1A_PEA_1_P36 (SEQ ID NO:810) HSMUC1A_PEA_1_P39 (SEQ ID NO:811) HSMUC1A_PEA_1_P45 (SEQ ID NO:812) HSMUC1A_PEA_1_P49 (SEQ ID NO:813) HSMUC1A_PEA_1_P52 (SEQ ID NO:814) HSMUC1A_PEA_1_P53 (SEQ ID NO:815) HSMUC1A_PEA_1_P56 (SEQ ID NO:816) HSMUC1A_PEA_1_P58 (SEQ ID NO:817) HSMUC1A_PEA_1_P59 (SEQ ID NO:818) HSMUC1A_PEA_1_P63 (SEQ ID NO:819)

[0149] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSMUC1A_PEA.sub.--1_P63 (SEQ ID NO:819), comprising a first amino acid sequence being at least 90% homologous to MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSV corresponding to amino acids 1-45 of MUC1_HUMAN (SEQ ID NO:805), which also corresponds to amino acids 1-45 of HSMUC1A_PEA.sub.--1_P63 (SEQ ID NO:819), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK (SEQ ID NO:946) corresponding to amino acids 46-85 of HSMUC1A_PEA.sub.--1_P63 (SEQ ID NO:819), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0150] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSMUC1A_PEA.sub.--1_P63 (SEQ ID NO:819), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EEEVSADQVSVGASGVLGSFKEARNAPSFLSWSFSMGPSK (SEQ ID NO:946) in HSMUC1A_PEA.sub.--1_P63 (SEQ ID NO:819).

[0151] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P2 (SEQ ID NO:664), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1-498 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-498 of T46984_PEA.sub.--1_P2 (SEQ ID NO:664), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VCA corresponding to amino acids 499-501 of T46984_PEA.sub.--1_P2 (SEQ ID NO:664), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0152] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P3 (SEQ ID NO:665), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQ corresponding to amino acids 1-433 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-433 of T46984_PEA.sub.--1_P3 (SEQ ID NO:665), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ICHIWKLIFLP (SEQ ID NO:947) corresponding to amino acids 434-444 of T46984_PEA.sub.--1_P3 (SEQ ID NO:665), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0153] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA.sub.--1_P3 (SEQ ID NO:665), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ICHIWKLIFLP (SEQ ID NO:947) in T46984_PEA.sub.--1_P3 (SEQ ID NO:665).

[0154] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P10 (SEQ ID NO:666), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNV corresponding to amino acids 1-498 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-498 of T46984_PEA.sub.--1_P10 (SEQ ID NO:666), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LMDQK (SEQ ID NO:948) corresponding to amino acids 499-503 of T46984_PEA.sub.--1_P10 (SEQ ID NO:666), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0155] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA.sub.--1_P10 (SEQ ID NO:666), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LMDQK (SEQ ID NO:948) in T46984_PEA.sub.--1_P10 (SEQ ID NO:666).

[0156] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P11 (SEQ ID NO:667), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFAL FFQLVDVNTGAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDS ASGTYTLYLIIGDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLFREPEK RPPTVVSNTFTALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYVYWT QLNMFQTLKYLAILGSVTFLAGNRMLAQQAVKR corresponding to amino acids 1-628 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-628 of T46984_PEA.sub.--1_P11 (SEQ ID NO:667).

[0157] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P12 (SEQ ID NO:668), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMN corresponding to amino acids 1-338 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-338 of T46984_PEA.sub.--1_P12 (SEQ ID NO:668), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SQDLH (SEQ ID NO:949) corresponding to amino acids 339-343 of T46984_PEA.sub.--1_P12 (SEQ ID NO:668), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0158] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA.sub.--1_P12 (SEQ ID NO:668), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SQDLH (SEQ ID NO:949) in T46984_PEA.sub.--1_P12 (SEQ ID NO:668).

[0159] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P21 (SEQ ID NO:669), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence M corresponding to amino acids 1-1 of T46984_PEA.sub.--1_P21 (SEQ ID NO:669), and a second amino acid sequence being at least 90% homologous to KACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSSVTQIYHAV AALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSIVEEIEDLVA RLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNAIFSKKNFES LSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQPLTQATVKL EHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDNRYIANTVEL RVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFALFFQLVDVNT GAELTPHQTFVRLHNQKTGQEVVFVAEPDNKNVYKFELDTSERKIEFDSASGTYTLYLII GDATLKNPILWNVADVVIKFPEEEAPSTVLSQNLFTPKQEIQHLFREPEKRPPTVVSNTF TALILSPLLLLFALWIRIGANVSNFTFAPSTIIFHLGHAAMLGLMYVYWTQLNMFQTLKY LAILGSVTFLAGNRMLAQQAVKRTAH corresponding to amino acids 70-631 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 2-563 of T46984_PEA.sub.--1_P21 (SEQ ID NO:669), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0160] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P27 (SEQ ID NO:670), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVELRVKISTEVGITNVDLSTVDKDQSIAPKTTRVTYPAKAKGTFIADSHQNFA corresponding to amino acids 1-415 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-415 of T46984_PEA.sub.--1.sub.P27 (SEQ ID NO:670), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence FGSGLVPMSPTSLLLLARLYFTWDMLLCWDSCMSTGLSSTCSRP (SEQ ID NO:950) corresponding to amino acids 416-459 of T46984_PEA.sub.--1_P27 (SEQ ID NO:670), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0161] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA.sub.--1_P27 (SEQ ID NO:670), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence FGSGLVPMSPTSLLLLARLYFTWDMLLCWDSCMSTGLSSTCSRP (SEQ ID NO:950) in T46984_PEA.sub.--1_P27 (SEQ ID NO:670).

[0162] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P32 (SEQ ID NO:671), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVGDVFELNFMNVKFSSGYYDFLVEVEGDN RYIANTVE corresponding to amino acids 1-364 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-364 of T46984_PEA.sub.--1_P32 (SEQ ID NO:671), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT (SEQ ID NO:951) corresponding to amino acids 365-397 of T46984_PEA.sub.--1_P32 (SEQ ID NO:671), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0163] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA.sub.--1_P32 (SEQ ID NO:671), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GQVRWLTPVIPALWEAKAGGSPEVRSSILAWPT (SEQ ID NO:951) in T46984_PEA.sub.--1_P32 (SEQ ID NO:671).

[0164] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P34 (SEQ ID NO:672), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAILRLQVTNVLSQ PLTQATVKLEHAKSVASRATVLQKTSFTPVG corresponding to amino acids 1-329 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-329 of T46984_PEA.sub.--1.sub.13 P34 (SEQ ID NO:672).

[0165] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P35 (SEQ ID NO:673), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLATVQALQTASHLSQQADLRSI VEEIEDLVARLDELGGVYLQFEEGLETTALFVAATYKLMDHVGTEPSIKEDQVIQLMNA IFSKKNFESLSEAFSVASAAAVLSHNRYHVPVVVVPEGSASDTHEQAI corresponding to amino acids 1-287 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-287 of T46984_PEA.sub.--1_P35 (SEQ ID NO:673), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GCWPSRQSREQHISSRRKMEILKTECQEKESRTIHSMRRKMEKKNFI (SEQ ID NO:952) corresponding to amino acids 288-334 of T46984_PEA.sub.--1_P35 (SEQ ID NO:673), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0166] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA.sub.--1_P35 (SEQ ID NO:673), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GCWPSRQSREQHISSRRKMEILKTECQEKESRTIHSMRRKMEKKNFI (SEQ ID NO:952) in T46984_PEA.sub.--1_P35 (SEQ ID NO:673).

[0167] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P38 (SEQ ID NO:674), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEAL corresponding to amino acids 1-145 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-145 of T46984_PEA.sub.--1_P38 (SEQ ID NO:674), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDPDWCQCLQLHFCS (SEQ ID NO:953) corresponding to amino acids 146-160 of T46984_PEA.sub.--1_P38 (SEQ ID NO:674), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0168] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA.sub.--1_P38 (SEQ ID NO:674), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MDPDWCQCLQLHFCS (SEQ ID NO:953) in T46984_PEA.sub.--1_P38 (SEQ ID NO:674)

[0169] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P39 (SEQ ID NO:675), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCEISISNETKDLLLAAVSEDSS VTQIYHAVAALSGFGLPLASQEALSALTARLSKEETVLA corresponding to amino acids 1-160 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-160 of T46984_PEA.sub.--1_P39 (SEQ ID NO:675).

[0170] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P45 (SEQ ID NO:676), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAKKACTYIRSNLDPSNVDSLFYAAQASQALSGCE corresponding to amino acids 1-101 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-101 of T46984_PEA.sub.--1_P45 (SEQ ID NO:676), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) corresponding to amino acids 102-116 of T46984_PEA.sub.--1_P45 (SEQ ID NO:676), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0171] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA.sub.--1_P45 (SEQ ID NO:676), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) in T46984_PEA.sub.--1_P45 (SEQ ID NO:676).

[0172] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T46984_PEA.sub.--1_P46 (SEQ ID NO:677), comprising a first amino acid sequence being at least 90% homologous to MAPPGSSTVFLLALTIIASTWALTPTHYLTKHDVERLKASLDRPFTNLESAFYSIVGLSSL GAQVPDAK corresponding to amino acids 1-69 of RIB2_HUMAN (SEQ ID NO:663), which also corresponds to amino acids 1-69 of T46984_PEA.sub.--1_P46 (SEQ ID NO:677), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) corresponding to amino acids 70-84 of T46984_PEA.sub.--1_P46 (SEQ ID NO:677), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0173] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T46984_PEA.sub.--1_P46 (SEQ ID NO:677), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NSPGSADSIPPVPAG (SEQ ID NO:954) in T46984_PEA.sub.--1_P46 (SEQ ID NO:677).

[0174] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T11628_PEA.sub.--1_P2 (SEQ ID NO:712), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956) corresponding to amino acids 1-55 of T11628_PEA.sub.--1_P2 (SEQ ID NO:712), and a second amino acid sequence being at least 90% homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of Q8WVH6 (SEQ ID NO:711), which also corresponds to amino acids 56-154 of T11628_PEA.sub.--1_P2 (SEQ ID NO:712), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0175] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T11628_PEA.sub.--1_P2 (SEQ ID NO:712), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00071 MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956) of T11628_PEA_1_P2. (SEQ ID NO:712)

[0176] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T11628_PEA.sub.--1_P5 (SEQ ID NO:713), comprising a first amino acid sequence being at least 90% homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 56-154 of MYG_HUMAN_V1 (SEQ ID NO:710), which also corresponds to amino acids 1-99 of T11628_PEA.sub.--1_P5 (SEQ ID NO:713).

[0177] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T11628_PEA.sub.--1_P7 (SEQ ID NO:714), comprising a first amino acid sequence being at least 90% homologous to MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMK ASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQ SKHPGDFGADAQGAMNK corresponding to amino acids 1-134 of MYG_HUMAN_V1 (SEQ ID NO:710), which also corresponds to amino acids 1-134 of T11628_PEA.sub.--1_P7 (SEQ ID NO:714) and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence G corresponding to amino acids 135-135 of T11628_PEA.sub.--1_P7 (SEQ ID NO:714), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0178] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T11628_PEA.sub.--1_P10 (SEQ ID NO:715), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956) corresponding to amino acids 1-55 of T111628_PEA.sub.--1_P10 (SEQ ID NO:715), and a second amino acid sequence being at least 90% homologous to MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQV LQSKHPGDFGADAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of Q8WVH6 (SEQ ID NO:711), which also corresponds to amino acids 56-154 of T11628_PEA.sub.--1_P10 (SEQ ID NO:715), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0179] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T11628_PEA.sub.--1_P10 (SEQ ID NO:715), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:956) of T11628_PEA.sub.--1_P10 (SEQ ID NO:715).

[0180] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA.sub.--1_P3 (SEQ ID NO:761), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKD corresponding to amino acids 1-517 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-517 of M78076_PEA.sub.--1_P3 (SEQ ID NO:761), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GE corresponding to amino acids 518-519 of M78076_PEA.sub.--1_P3 (SEQ ID NO:761), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0181] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA.sub.--1_P4 (SEQ ID NO:762), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids 1-526 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-526 of M78076_PEA.sub.--1_P4 (SEQ ID NO:762), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ECLTVNPSLQIPLNP (SEQ ID NO:958) corresponding to amino acids 527-541 of M78076_PEA.sub.--1_P4 (SEQ ID NO:762), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0182] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA.sub.--1_P4 (SEQ ID NO:762), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ECLTVNPSLQIPLNP (SEQ ID NO:958) in M78076_PEA.sub.--1_P4 (SEQ ID NO:762).

[0183] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA.sub.--1_P12 (SEQ ID NO:763), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids 1-526 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-526 of M78076_PEA.sub.--1_P12 (SEQ ID NO:763), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ECVCSKGFPFPLIGDSEG (SEQ ID NO:959) corresponding to amino acids 527-544 of M78076_PEA.sub.--1_P12 (SEQ ID NO:763), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0184] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA.sub.--1_P12 (SEQ ID NO:763), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ECVCSKGFPFPLIGDSEG (SEQ ID NO:959) in M78076_PEA.sub.--1_P12 (SEQ ID NO:763).

[0185] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA.sub.--1_P14 (SEQ ID NO:764), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGST EQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDEL corresponding to amino acids 1-570 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-570 of M78076_PEA.sub.--1_P14 (SEQ ID NO:764), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO:960) corresponding to amino acids 571-619 of M78076_PEA.sub.--1_P14 (SEQ ID NO:764), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0186] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA.sub.--1_P14 (SEQ ID NO:764), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO:960) in M78076_PEA.sub.--1_P14 (SEQ ID NO:764).

[0187] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA.sub.--1_P21 (SEQ ID NO:765), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN E corresponding to amino acids 1-352 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-352 of M78076_PEA.sub.--1_P21 (SEQ ID NO:765), and a second amino acid sequence being at least 90% homologous to AERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQ SLGLLDQNPHLAQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMT LPKGSTEQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSEIQRDELAPAGTGVSREA VSGLLIMGAGGGSLIVLSMLLLRRKKPYGAISHGVVEVDPMLTLEEQQLRELQRHGYE NPTYRFLEERP corresponding to amino acids 406-650 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 353-597 of M78076_PEA.sub.--1_P21 (SEQ ID NO:765), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0188] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of M78076_PEA.sub.--1_P21 (SEQ ID NO:765), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EA, having a structure as follows: a sequence starting from any of amino acid numbers 352-x to 352; and ending at any of amino acid numbers 353+((n-2)-x), in which x varies from 0 to n-2.

[0189] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA.sub.--1_P24 (SEQ ID NO:766), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLD QNPHLAQELRPQI corresponding to amino acids 1-481 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-481 of M78076_PEA.sub.--1_P24 (SEQ ID NO:766), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RECLLPWLPLQISEGRS (SEQ ID NO:961) corresponding to amino acids 482-498 of M78076_PEA.sub.--1_P24 (SEQ ID NO:766), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0190] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA.sub.--1_P24 (SEQ ID NO:766), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RECLLPWLPLQISEGRS (SEQ ID NO:961) in M78076_PEA.sub.--1_P24 (SEQ ID NO:766).

[0191] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA.sub.--1_P2 (SEQ ID NO:767), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQV corresponding to amino acids 1-449 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-449 of M78076_PEA.sub.--1_P2 (SEQ ID NO:767), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLT CCVFDPCFLALGFLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIAT STSWVQAILLPQPLE (SEQ ID NO:962) corresponding to amino acids 450-588 of M78076_PEA.sub.--1_P2 (SEQ ID NO:767), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0192] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA.sub.--1_P2 (SEQ ID NO:767), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00072 LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLT (SEQ ID NO:962) CCVFDPCFLALGFLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIAT STSWVQAILLPQPLE in M78076_PEA_1_P2. (SEQ ID NO:767)

[0193] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78076_PEA.sub.--1_P25 (SEQ ID NO:768), comprising a first amino acid sequence being at least 90% homologous to MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGL CGRLTLHRDLRTGRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPME RWCGGSRSGSCAHPHHQVVPFRCLPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQ EAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCPPPGTPDPSGTAVGDPSTRSWPPG SRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGKVTPTPRPTDGV DIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALN EHFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLL ALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQ corresponding to amino acids 1-448 of APP1_HUMAN (SEQ ID NO:760), which also corresponds to amino acids 1-448 of M78076_PEA.sub.--1_P25 (SEQ ID NO:768), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP (SEQ ID NO:963) corresponding to amino acids 449-505 of M78076_PEA.sub.--1_P25 (SEQ ID NO:768), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0194] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M78076_PEA.sub.--1_P25 (SEQ ID NO:768), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP (SEQ ID NO:963) in M78076_PEA.sub.--1_P25 (SEQ ID NO:768).

[0195] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M85491_PEA.sub.--1_P13 (SEQ ID NO:246), comprising a first amino acid sequence being at least 90% homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPIN SRTTSEGATNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSG GREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAV NGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYEL QYYEK corresponding to amino acids 1-476 of EPB2_HUMAN (SEQ ID NO:245), which also corresponds to amino acids 1-476 of M85491_PEA.sub.--1_P13 (SEQ ID NO:246), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO:964) corresponding to amino acids 477-496 of M85491_PEA.sub.--1_P13 (SEQ ID NO:246), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0196] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M85491_PEA.sub.--1_P13 (SEQ ID NO:246), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO:964) in M85491_PEA.sub.--1_P13 (SEQ ID NO:246).

[0197] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M85491_PEA.sub.--1_P14 (SEQ ID NO:247), comprising a first amino acid sequence being at least 90% homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR corresponding to amino acids 1-270 of EPB2_HUMAN (SEQ ID NO:245), which also corresponds to amino acids 1-270 of M85491_PEA.sub.--1_P14 (SEQ ID NO:247), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO:965) corresponding to amino acids 271-301 of M85491_PEA.sub.--1_P14 (SEQ ID NO:247), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0198] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of M85491_PEA.sub.--1_P14 (SEQ ID NO:247), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO:965) in M85491_PEA.sub.--1_P14 (SEQ ID NO:247).

[0199] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P4 (SEQ ID NO:271), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P4 (SEQ ID NO:271), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P4 (SEQ ID NO:271), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQGAQYWVYDGEKPVLGPAPLTELGLVRFPVHAALVWGPE KNKIYFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDADG corresponding to amino acids 165-445 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-445 of HSSTROL3_P4 (SEQ ID NO:271), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:966) corresponding to amino acids 446-496 of HSSTROL3_P4 (SEQ ID NO:271), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

[0200] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P4 (SEQ ID NO:271), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:966) in HSSTROL3_P4 (SEQ ID NO:271).

[0201] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL.sup.3_P5 (SEQ ID NO:272), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P5 (SEQ ID NO:272), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P5 (SEQ ID NO:272), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQ corresponding to amino acids 165-358 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-358 of HSSTROL3_P5 (SEQ ID NO:272), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO:967) corresponding to amino acids 359-382 of HSSTROL3_P5 (SEQ ID NO:272), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

[0202] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P5 (SEQ ID NO:272), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO:967) in HSSTROL3_P5 (SEQ ID NO:272).

[0203] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P7 (SEQ ID NO:273), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P7 (SEQ ID NO:273), a bridging amino acid H corresponding to amino acid 164 of HSSTROL3_P7 (SEQ ID NO:273), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-359 of HSSTROL3_P7 (SEQ ID NO:273), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID NO:968) corresponding to amino acids 360-370 of HSSTROL3_P7 (SEQ ID NO:273), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

[0204] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P7 (SEQ ID NO:273), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:968) in HSSTROL3_P7 (SEQ ID NO:273).

[0205] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P8 (SEQ ID NO:274), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFP WQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-163 of HSSTROL3_P8 (SEQ ID NO:274), a bridging amino acid H corresponding to amino acid 164of HSSTROL3_P8 (SEQ ID NO:274), a second amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLE corresponding to amino acids 165-286 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 165-286 of HSSTROL3_P8 (SEQ ID NO:274), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRPCLPVPLLLCWPL (SEQ ID NO:969) corresponding to amino acids 287-301 of HSSTROL3_P8 (SEQ ID NO:274), wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

[0206] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P8 (SEQ ID NO:274), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRPCLPVPLLLCWPL (SEQ ID NO:969) in HSSTROL3_P8 (SEQ ID NO:274).

[0207] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSSTROL3_P9 (SEQ ID NO:275), comprising a first amino acid sequence being at least 90% homologous to MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSS PAPAPATQEAPRPASSLRPPRCGVPDPSDGLSARNRQK corresponding to amino acids 1-96 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 1-96 of HSSTROL3_P9 (SEQ ID NO:275), a second amino acid sequence being at least 90% homologous to RILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 113-163 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 97-147 of HSSTROL3_P9 (SEQ ID NO:275), a bridging amino acid H corresponding to amino acid 148 of HSSTROL3_P9 (SEQ ID NO:275), a third amino acid sequence being at least 90% homologous to GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLG LQHTTAAKALMSAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTN EIAPLEPDAPPDACEASFDAVSTIRGELFFFKAGFVWRLRGGQLQPGYPALASRHWQGL PSPVDAAFEDAQGHIWFFQG corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID NO:270), which also corresponds to amino acids 149-343 of HSSTROL3_P9 (SEQ ID NO:275), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID NO:968) corresponding to amino acids 344-354 of HSSTROL3_P9 (SEQ ID NO:275), wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

[0208] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HSSTROL3_P9 (SEQ ID NO:275), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KR, having a structure as follows: a sequence starting from any of amino acid numbers 96-x to 96; and ending at any of amino acid numbers 97+((n-2)-x), in which x varies from 0 to n-2.

[0209] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSSTROL3_P9 (SEQ ID NO:275), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:968) in HSSTROL3_P9 (SEQ ID NO:275).

[0210] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AY180924_PEA.sub.--1_P3 (SEQ ID NO:281), comprising a first amino acid sequence being at least 90% homologous to MLNVSGLFVLLCGLLVSSSAQEVLAGVSSQLLN corresponding to amino acids 1-33 of LATH_HUMAN (SEQ ID NO:280), which also corresponds to amino acids 1-33 of AY180924_PEA.sub.--1_P3 (SEQ ID NO:281), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GETVLLWVMQNPEPMPVKFSLAKYLGHNEHY (SEQ ID NO:971) corresponding to amino acids 34-64 of AY180924_PEA.sub.--1_P3 (SEQ ID NO:281), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0211] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of AY180924_PEA.sub.--1_P3 (SEQ ID NO:281), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GETVLLWVMQNPEPMPVKFSLAKYLGHNEHY (SEQ ID NO:971) in AY180924_PEA.sub.--1_P3 (SEQ ID NO:281).

[0212] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R75793_PEA.sub.--1_P2 (SEQ ID NO:295), comprising a first amino acid sequence being at least 90% homologous to MKFLAVLVLLGVSIFLVSAQNPTTAAPADTYPATGPADDEAPDAETTAAATTATTAAPT TATTAASTTARKDIP corresponding to amino acids 1-74 of Q96DR8 (SEQ ID NO:294), which also corresponds to amino acids 1-74 of R75793_PEA.sub.--1_P2 (SEQ ID NO:295), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AP corresponding to amino acids 75-76 of R75793_PEA.sub.--1_P2 (SEQ ID NO:295), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0213] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCA1XIA_P14 (SEQ ID NO:350), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGYPGPRGVK GADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPT GDPGPSGQAGEKGKLGVPGLPGYPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPR GQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGP PGKDGLPGHPGQRGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQG LPGAAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQGPPGP V corresponding to amino acids 1-1056 of CA1B_HUMAN_V5 (SEQ ID NO:349), which also corresponds to amino acids 1-1056 of HUMCA1XIA_P14 (SEQ ID NO:350), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO:972) corresponding to amino acids 1057-1081 of HUMCA1XIA_P14 (SEQ ID NO:350), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0214] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCA1XIA_P14 (SEQ ID NO:350), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO:972) in HUMCA1XIA_P14 (SEQ ID NO:350).

[0215] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCA1XIA_P15 (SEQ ID NO:351 ), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEK corresponding to amino acids 1-714 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 1-714 of HUMCA1XIA_P15 (SEQ ID NO:351), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MCCNLSFGILIPLQK (SEQ ID NO:973) corresponding to amino acids 715-729 of HUMCA1XIA_P15 (SEQ ID NO:351), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0216] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCA1XIA_P15 (SEQ ID NO :351 ), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MCCNLSFGILIPLQK (SEQ ID NO:973) in HUMCA1XIA_P15 (SEQ ID NO:351).

[0217] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCA1XIA_P16 (SEQ ID NO:352), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEA corresponding to amino acids 1-648 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 1-648 of HUMCA1XIA_P16 (SEQ ID NO:352), a second amino acid sequence being at least 90% homologous to GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK corresponding to amino acids 667-714 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 649-696 of HUMCA1XIA_P16 (SEQ ID NO:352), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO:974) corresponding to amino acids 697-738 of HUMCA1XIA_P16 (SEQ ID NO:352), wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

[0218] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCA1XIA_P16 (SEQ ID NO:352), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise AG, having a structure as follows: a sequence starting from any of amino acid numbers 648-x to 648; and ending at any of amino acid numbers 649+((n-2)-x), in which x varies from 0 to n-2.

[0219] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCA1XIA_P16 (SEQ ID NO:352), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO:974) in HUMCA1XIA_P16 (SEQ ID NO:352).

[0220] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCA1XIA_P17 (SEQ ID NO:353), comprising a first amino acid sequence being at least 90% homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDE corresponding to amino acids 1-260 of CA1B_HUMAN (SEQ ID NO:348), which also corresponds to amino acids 1-260 of HUMCA1XIA_P17 (SEQ ID NO:353), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRSTRPEKVFVFQ (SEQ ID NO:975) corresponding to amino acids 261-273 of HUMCA1XIA_P17 (SEQ ID NO:353), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0221] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCA1XIA_P17 (SEQ ID NO:353), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRSTRPEKVFVFQ (SEQ ID NO:975) in HUMCA1XIA_P17 (SEQ ID NO:353).

[0222] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R20779_P2 (SEQ ID NO:380), comprising a first amino acid sequence being at least 90% homologous to MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNTAEIQHCLV NAGDVGCGVFECFENNSCEIRGLHGICMTFLHNAGKFDAQGKSFIKDALKCKAHALRH RFGCISRKCPAIREMVSQLQRECYLKHDLCAAAQENTRVIVEMIHFKDLLLHE corresponding to amino acids 1-169 of STC2_HUMAN (SEQ ID NO:379), which also corresponds to amino acids 1-169 of R20779_P2 (SEQ ID NO:380), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CYKIEITMPKRRKVKLRD (SEQ ID NO:976) corresponding to amino acids 170-187 of R20779_P2 (SEQ ID NO:380), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0223] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R20779_P2 (SEQ ID NO:380), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CYKIEITMPKRRKVKLRD (SEQ ID NO:976) in R20779_P2 (SEQ ID NO:380).

[0224] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P3 (SEQ ID NO:488), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTV corresponding to amino acids 1-865 of CO4_HUMAN, which also corresponds to amino acids 1-865 of HSCOC4_PEA.sub.--1_P3 (SEQ ID NO:488), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RPHRSLSIQELGEPGPSEGWGG (SEQ ID NO:977) corresponding to amino acids 866-887 of HSCOC4_PEA.sub.--1_P3 (SEQ ID NO:488), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0225] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P3 (SEQ ID NO:488), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RPHRSLSIQELGEPGPSEGWGG (SEQ ID NO:977) in HSCOC4_PEA.sub.--1_P3 (SEQ ID NO:488).

[0226] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P5 (SEQ ID NO:489), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKG corresponding to amino acids 1-818 of CO4_HUMAN, which also corresponds to amino acids 1-818 of HSCOC4_PEA.sub.--1_P5 (SEQ ID NO:489), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) corresponding to amino acids 819-843 of HSCOC4_PEA.sub.--1_P5 (SEQ ID NO:489), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0227] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P5 (SEQ ID NO:489), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) in HSCOC4_PEA.sub.--1_P5 (SEQ ID NO:489).

[0228] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P6 (SEQ ID NO:490), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKG corresponding to amino acids 1-1052 of CO4_HUMAN, which also corresponds to amino acids 1-1052 of HSCOC4_PEA.sub.--1_P6 (SEQ ID NO:490), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP (SEQ ID NO:979) corresponding to amino acids 1053-1084 of HSCOC4_PEA.sub.--1_P6 (SEQ ID NO:490), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0229] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P6 (SEQ ID NO:490), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGCKGKQEGGQERTVTGRWTAQEATEGKKGGP (SEQ ID NO:979) in HSCOC4_PEA.sub.--1_P6 (SEQ ID NO:490).

[0230] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P12 (SEQ ID NO:491), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKV corresponding to amino acids 1-1380 of CO4_HUMAN_V1(SEQ ID NO:486), which also corresponds to amino acids 1-1380 of HSCOC4_PEA.sub.--1_P12 (SEQ ID NO:491), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RAREGVGPGTGGGEGVE (SEQ ID NO:980) corresponding to amino acids 1381-1397 of HSCOC4_PEA.sub.--1_P12 (SEQ ID NO:491), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0231] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P12 (SEQ ID NO:491), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RAREGVGPGTGGGEGVE (SEQ ID NO:980) in HSCOC4_PEA.sub.--1_P12 (SEQ ID NO:491).

[0232] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P15 (SEQ ID NO:492), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQ corresponding to amino acids 1-1359 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1359 of HSCOC4_PEA.sub.--1_P15 (SEQ ID NO:492), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL (SEQ ID NO:981) corresponding to amino acids 1360-1415 of HSCOC4_PEA.sub.--1_P15 (SEQ ID NO:492), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0233] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P15 (SEQ ID NO:492), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VNHSLVNHSLAWVARTPGPRGQARSRPQPPTRGIPAALLPGVFGGRLTSWLRDLEL (SEQ ID NO:981) in HSCOC4_PEA.sub.--1_P15 (SEQ ID NO:492).

[0234] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P16 (SEQ ID NO:493), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPK corresponding to amino acids 1-1457 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1457 of HSCOC4_PEA.sub.--1_P16 (SEQ ID NO:493), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AERQGGAVWHGHRGRHPPEWIPRPAC (SEQ ID NO:982) corresponding to amino acids 1458-1483 of HSCOC4_PEA.sub.--1_P16 (SEQ ID NO:493), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0235] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P16 (SEQ ID NO:493), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AERQGGAVWHGHRGRHPPEWIPRPAC (SEQ ID NO:982) in HSCOC4_PEA.sub.--1_P16 (SEQ ID NO:493).

[0236] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P20 (SEQ ID NO:494), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQ corresponding to amino acids 1-1303 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1303 of HSCOC4_PEA.sub.--1_P20 (SEQ ID NO:494), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH (SEQ ID NO:983) corresponding to amino acids 1304-1349 of HSCOC4_PEA.sub.--1_P20 (SEQ ID NO:494), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0237] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P20 (SEQ ID NO:494), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00073 (SEQ ID NO: 983) VGAVPGLWRGWVVLRPRACLSPGSTSLGHGDCPGCPVCLLDCLPHH (SEQ ID NO: 494) in HSCOC4_PEA_1_P20.

[0238] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P9 (SEQ ID NO:495), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSV corresponding to amino acids 1-1529 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1529 of HSCOC4_PEA.sub.--1_P9 (SEQ ID NO:495), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGER (SEQ ID NO:984) corresponding to amino acids 1530-1533 of HSCOC4_PEA.sub.--1_P9 (SEQ ID NO:495), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0239] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P9 (SEQ ID NO:495), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGER (SEQ ID NO:984) in HSCOC4_PEA.sub.--1_P9 (SEQ ID NO:495).

[0240] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P22 (SEQ ID NO:496), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAF RLFETKITQVLHF corresponding to amino acids 1-1653 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1653 of HSCOC4_PEA.sub.--1_P22 (SEQ ID NO:496), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SMKQTGEAGRAGGRQGG (SEQ ID NO:985) corresponding to amino acids 1654-1670 of HSCOC4_PEA.sub.--1_P22 (SEQ ID NO:496), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0241] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P22 (SEQ ID NO:496), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SMKQTGEAGRAGGRQGG (SEQ ID NO:985) in HSCOC4_PEA.sub.--1_P22 (SEQ ID NO:496).

[0242] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P23 (SEQ ID NO:497), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYG corresponding to amino acids 1-1626 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1626 of HSCOC4_PEA.sub.--1_P23 (SEQ ID NO:497), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNSPFPLLLTPS (SEQ ID NO:986) corresponding to amino acids 1627-1685 of HSCOC4_PEA.sub.--1_P23 (SEQ ID NO:497), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0243] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P23 (SEQ ID NO:497), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence QSSHRGPGLTLPRGPAVLVSLGVACSSYRSCTQPVCSDTNFLPSQPQSNSPFPLLLTPS (SEQ ID NO:986) in HSCOC4_PEA.sub.--1_P23 (SEQ ID NO:497).

[0244] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P24 (SEQ ID NO:498), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDS corresponding to amino acids 1-1528 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1528 of HSCOC4_PEA.sub.--1_P24 (SEQ ID NO:498), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRTRMATG (SEQ ID NO:987) corresponding to amino acids 1529-1579 of HSCOC4_PEA.sub.--1_P24 (SEQ ID NO:498), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0245] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P24 (SEQ ID NO:498), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00074 SADVLCFTGHQVRADSWPPCVLLKSASVLRGSALASVAPWSGVCRTRMATG (SEQ ID NO: 987) in HSCOC4_PEA_1_P24. (SEQ ID NO: 498)

[0246] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P25 (SEQ ID NO:499), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids 1-1593 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1593 of HSCOC4_PEA.sub.--1_P25 (SEQ ID NO:499), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC GVRLPG (SEQ ID NO:988) corresponding to amino acids 1594-1657 of HSCOC4_PEA.sub.--1_P25 (SEQ ID NO:499), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0247] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P25 (SEQ ID NO:499), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00075 ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC (SEQ ID NO: 988) GVRLPG in HSCOC4_PEA_1_P25. (SEQ ID NO: 499)

[0248] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P26 (SEQ ID NO:500), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLC SAEVCQCAEG corresponding to amino acids 1-1593 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1593 of HSCOC4_PEA.sub.--1_P26 (SEQ ID NO:500), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TABLE-US-00076 ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC (SEQ ID NO: 989) GVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL

corresponding to amino acids 1594-1691 of HSCOC4_PEA.sub.--1_P26 (SEQ ID NO:500), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0249] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P26 (SEQ ID NO:500), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00077 ETEGLGRGSGGGMAGAPPTLSDGFPNFREVPSPASRPGAGSAGRGWLQDEVCLLLPPC (SEQ ID NO: 989) GVRSVFPPRPWPDPPSGTGCFGLSGCSLLLLQVMHAACLL in HSCOC4_PEA_1_P26. (SEQ ID NO: 500)

[0250] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P30 (SEQ ID NO:501), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGS corresponding to amino acids 1-1232 of CO4_HUMAN_V3 (SEQ ID NO:487), which also corresponds to amino acids 1-1232 of HSCOC4_PEA.sub.--1_P30 (SEQ ID NO:501), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RNPVRLLQPRAQMFCVLRGTK (SEQ ID NO:990) corresponding to amino acids 1233-1253 of HSCOC4_PEA.sub.--1_P30 (SEQ ID NO:501), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0251] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P30 (SEQ ID NO:501), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RNPVRLLQPRAQMFCVLRGTK (SEQ ID NO:990) in HSCOC4_PEA.sub.--1_P30 (SEQ ID NO:501).

[0252] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P38 (SEQ ID NO:502), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKG corresponding to amino acids 1-818 of CO4_HUMAN, which also corresponds to amino acids 1-818 of HSCOC4_PEA.sub.--1_P38 (SEQ ID NO:502), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) corresponding to amino acids 819-843 of HSCOC4_PEA.sub.--1_P38 (SEQ ID NO:502), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0253] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P38 (SEQ ID NO:502), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVTLSGPQVTLLPFPCTPAPCSLCS (SEQ ID NO:978) in HSCOC4_PEA.sub.--1_P38 (SEQ ID NO:502).

[0254] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P39 (SEQ ID NO:503), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQ corresponding to amino acids 1-387 of CO4_HUMAN, which also corresponds to amino acids 1-387 of HSCOC4_PEA.sub.--1_P39 (SEQ ID NO:503), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSSRGEG (SEQ ID NO:992) corresponding to amino acids 388-394 of HSCOC4_PEA.sub.--1_P39 (SEQ ID NO:503), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0255] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P39 (SEQ ID NO:503), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSSRGEG (SEQ ID NO:992) in HSCOC4_PEA.sub.--1_P39 (SEQ ID NO:503).

[0256] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P40 (SEQ ID NO:504), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKY corresponding to amino acids 1-236 of CO4_HUMAN, which also corresponds to amino acids 1-236 of HSCOC4_PEA.sub.--1_P40 (SEQ ID NO:504), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGEWTEPHFPLKGRVPGRPGEAEYGHY (SEQ ID NO:993) corresponding to amino acids 237-263 of HSCOC4_PEA.sub.--1_P40 (SEQ ID NO:504), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0257] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P40 (SEQ ID NO:504), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AGEWTEPHFPLKGRVPGRPGEAEYGHY (SEQ ID NO:993) in HSCOC4_PEA.sub.--1_P40 (SEQ ID NO:504).

[0258] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P41 (SEQ ID NO:505), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLL YFDSV corresponding to amino acids 1-1529 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1529 of HSCOC4_PEA.sub.--1_P41 (SEQ ID NO:505), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGER (SEQ ID NO:984) corresponding to amino acids 1530-1533 of HSCOC4_PEA.sub.--1_P41 (SEQ ID NO:505), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0259] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1.sub.--l P41 (SEQ ID NO:505), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SGER (SEQ ID NO:984) in HSCOC4_PEA.sub.--1_P41 (SEQ ID NO:505).

[0260] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSCOC4_PEA.sub.--1_P42 (SEQ ID NO:506), comprising a first amino acid sequence being at least 90% homologous to MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLR NPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLK DSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMV ENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVL PNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFR GLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAE LTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVP EVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPD SRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLA PSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDS LALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAG LAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTR LPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLID EDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQL RVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQ QVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREEL VYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASL LRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRK ADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQ DPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASS FLGEKASAGLLGAHAAAITAYALTLTKAPADLRGVAHNNLMAMAQETGDNLYWGSV TGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQAAAWLTR QGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQ IRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVE YTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRV HYTVCIW corresponding to amino acids 1-1473 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1-1473 of HSCOC4_PEA.sub.--1_P42 (SEQ ID NO:506), a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR (SEQ ID NO:1021) corresponding to amino acids 1474-1511 of HSCOC4_PEA.sub.--1_P42 (SEQ ID NO:506), a third amino acid sequence being at least 90% homologous to RNGKVGLSGMAIADVTLLSGFHALRADLEK corresponding to amino acids 1474-1503 of CO4_HUMAN_V1 (SEQ ID NO:486), which also corresponds to amino acids 1512-1541 of HSCOC4_PEA.sub.--1_P42 (SEQ ID NO:506), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VWSATQGNPLCPRY (SEQ ID NO:995) corresponding to amino acids 1542-1555 of HSCOC4_PEA.sub.--1_P42 (SEQ ID NO:506), wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

[0261] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of HSCOC4_PEA.sub.--1_P42 (SEQ ID NO:506), comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for WAPGAALGQGREGRTQAGAGLLEPAQAEPGRQLTRLHR (SEQ ID NO: 1021), corresponding to HSCOC4_PEA.sub.--1_P42 (SEQ ID NO:506).

[0262] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSCOC4_PEA.sub.--1_P42 (SEQ ID NO:506), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VWSATQGNPLCPRY (SEQ ID NO:995) in HSCOC4_PEA.sub.--1_P42 (SEQ ID NO:506).

[0263] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:518), comprising a first amino acid sequence being at least 90% homologous to MAARALCMLGLVLALLSSSSAEEYVGL corresponding to amino acids 1-27 of TFF3_HUMAN (SEQ ID NO:516), which also corresponds to amino acids 1-27 of HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:518), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WKVHLPKGEGFSSG (SEQ ID NO:996) corresponding to amino acids 28-41 of HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:518), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0264] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:518), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence WKVHLPKGEGFSSG (SEQ ID NO:996) in HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:518).

[0265] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:553), comprising a first amino acid sequence being at least 90% homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQ corresponding to amino acids 1-58 of OSTP_HUMAN (SEQ ID NO:552), which also corresponds to amino acids 1-58 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:553), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VFLNFS (SEQ ID NO:997) corresponding to amino acids 59-64 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:553), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0266] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:553), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VFLNFS (SEQ ID NO:997) in HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:553).

[0267] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:554), comprising a first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31 of OSTP_HUMAN (SEQ ID NO:552), which also corresponds to amino acids 1-31 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:554), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence H corresponding to amino acids 32-32 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:554), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0268] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:555), comprising a first amino acid sequence being at least 90 % homologous to MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31 of OSTP_HUMAN (SEQ ID NO:552), which also corresponds to amino acids 1-31 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:555), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSIFYVFI (SEQ ID NO:998)corresponding to amino acids 32-39 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:555), wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

[0269] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:555), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSIFYVFI (SEQ ID NO:998)in HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:555).

[0270] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA.sub.--1_P2 (SEQ ID NO:14), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVS corresponding to amino acids 1-319 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-319 of T10888_PEA.sub.--1_P2 (SEQ ID NO:14), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DWTRP (SEQ ID NO:999)corresponding to amino acids 320-324 of T10888_PEA.sub.--1_P2 (SEQ ID NO:14), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0271] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P2 (SEQ ID NO:14), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DWTRP (SEQ ID NO:999)in T10888_PEA.sub.--1_P2 (SEQ ID NO:14).

[0272] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA..sub.--1_P4 (SEQ ID NO:15), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL corresponding to amino acids 1-234 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-234 of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000)corresponding to amino acids 235-256 of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0273] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000)in T10888_PEA.sub.--1_P4 (SEQ ID NO:15).

[0274] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA.sub.--1_P4 (SEQ ID NO:15), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL corresponding to amino acids 1-234 of Q13774, which also corresponds to amino acids 1-234 of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000)corresponding to amino acids 235-256 of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0275] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000)in T10888_PEA.sub.--1_P4 (SEQ ID NO:15).

[0276] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA.sub.--1_P5 (SEQ ID NO:16), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVSG corresponding to amino acids 1-320 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-320 of T10888_PEA.sub.--1_P5 (SEQ ID NO:16), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV (SEQ ID NO:1001)corresponding to amino acids 321-390 of T10888_PEA.sub.--1_P5 (SEQ ID NO:16), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0277] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P5 (SEQ ID NO:16), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00078 KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF (SEQ ID NO: 1001) VVFCFLISHV in T10888_PEA_1_P5. (SEQ ID NO: 16)

[0278] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T10888_PEA.sub.--1_P6 (SEQ ID NO:17), comprising a first amino acid sequence being at least 90% homologous to TABLE-US-00079 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLA HNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQ NDTGFYTLQVIKSDLVNEEATGQFHVY

[0279] corresponding to amino acids 1-141 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-141 of T10888_PEA.sub.131_P6 (SEQ ID NO:17), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TABLE-US-00080 (SEQ ID NO: 1002) REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI

[0280] corresponding to amino acids 142-183 of T10888_PEA.sub.--1_P6 (SEQ ID NO:17), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0281] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P6 (SEQ ID NO:17), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI (SEQ ID NO:1002) in T10888_PEA.sub.--1_P6 (SEQ IDNO:17.

[0282] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P6 (SEQ ID NO:51), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG corresponding to amino acids 1-276 of VTNC_HUMAN, which also corresponds to amino acids 1-276 of T39971_P6 (SEQ ID NO:51), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TQGVVGD (SEQ ID NO:1003) corresponding to amino acids 277-283 of T39971_P6 (SEQ ID NO:51), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0283] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T39971_P6 (SEQ ID NO:51), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TQGVVGD (SEQ ID NO:1003) in T39971_P6 (SEQ ID NO:51).

[0284] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P9 (SEQ ID NO:52), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRT corresponding to amino acids 1-325 of VTNC_HUMAN, which also corresponds to amino acids 1-325 of T39971_P9 (SEQ ID NO:52), and a second amino acid sequence being at least 90% homologous to SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRATWLSLFSSEESNLGA NNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLRTRRVDTVDPPYPRSIAQYWLGC PAPGHL corresponding to amino acids 357-478 of VTNC_HUMAN, which also corresponds to amino acids 326-447 of T39971_P9 (SEQ ID NO:52), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0285] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T39971_P9 (SEQ ID NO:52) comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TS, having a structure as follows: a sequence starting from any of amino acid numbers 325-x to 325; and ending at any of amino acid numbers 326+((n-2)-x), in which x varies from 0 to n-2.

[0286] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P11 (SEQ ID NO:53), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1-326 of VTNC_HUMAN, which also corresponds to amino acids 1-326 of T39971_P11 (SEQ ID NO:53), and a second amino acid sequence being at least 90% homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of VTNC_HUMAN, which also corresponds to amino acids 327-363 of T39971_P11 (SEQ ID NO:53), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0287] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T39971_P11 (SEQ ID NO:53), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327+((n-2)-x), in which x varies from 0 to n-2.

[0288] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P11 (SEQ ID NO:53), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1-326 of Q9BSH7, which also corresponds to amino acids 1-326 of T39971_P11 (SEQ ID NO:53), and a second amino acid sequence being at least 90% homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of Q9BSH7, which also corresponds to amino acids 327-363 of T39971_P11 (SEQ ID NO:53), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0289] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T39971_P11 (SEQ ID NO:53), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327+((n-2)-x), in which x varies from 0 to n-2.

[0290] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P12 (SEQ ID NO:54), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1-223 of VTNC_HUMAN, which also corresponds to amino acids 1-223 of T39971_P12 (SEQ ID NO:54), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV (SEO ID NO:1004) corresponding to amino acids 224-238 of T39971_P12 (SEQ ID NO:54 , wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0291] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T39971_P12 (SEQ ID NO:54), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) in T39971_P12 (SEQ ID NO:54) According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T39971_P12 (SEQ ID NO:54), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1-223 of Q9BSH7, which also corresponds to amino acids 1-223 of T39971_P12 (SEQ ID NO:54), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) corresponding to amino acids 224-238 of T39971_P12 (SEQ ID NO:54), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0292] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T39971_P12 (SEQ ID NO:54), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) in T39971_P12 (SEQ ID NO:54).

[0293] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P2 (SEO ID NO:97), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGK LRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQ GTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQ ASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYI DKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKE AAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWN corresponding to amino acids 1-761 of SUL1_HUMAN, which also corresponds to amino acids 1-761 of Z21368_PEA.sub.--1_P2 (SEQ ID NO:97), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO:1005) corresponding to amino acids 762-790 of Z21368_PEA.sub.--1_P2 (SEQ ID NO:97), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0294] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P2 (SEQ ID NO:97), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO:1005) in Z21368_PEA.sub.--1_P2 (SEQ ID NO:97).

[0295] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1-57 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 1-57 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), second bridging amino acid sequence comprising A, and a third amino acid sequence being at least 90% homologous to FFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITN ESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNM DKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYT ADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDT PPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHL PKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLY ARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFE GEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPT TVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKR RKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKER KEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNE THNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCN PRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 139-871 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 59-791 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

[0296] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least three amino acids comprise LAF having a structure as follows (numbering according to Z21368_PEA.sub.--1_P5 (SEQ ID NO:98) ): a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 59+((n-2)-x), in which x varies from 0 to n-2.

[0297] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME (SEQ ID NO:1006) corresponding to amino acids 1-751 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), and a second amino acid sequence being at least 90% homologous to LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 1-40 of AAH12997 (SEQ ID NO:841), which also corresponds to amino acids 752-791 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0298] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00081 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF (SEQ ID NO: 1006) GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME of Z21368_PEA_1_P5. (SEQ ID NO: 98)

[0299] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1-57 of SUL1_HUMAN, which also corresponds to amino acids 1-57 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), and a second amino acid sequence being at least 90% homologous to AFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLIT NESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPN MDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGL DTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSN HLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRN LYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVE FEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGP PTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHL KRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRK KERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRT VNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYK QCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 138-871 of SUL1_HUMAN, which also corresponds to amino acids 58-791 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0300] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise LA, having a structure as follows: a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 58+((n-2)-x), in which x varies from 0 to n-2.

[0301] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P15 (SEQ ID NO:99), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERG corresponding to amino acids 1-416 of SUL1_HUMAN, which also corresponds to amino acids 1-416 of Z21368_PEA.sub.--1_P15 (SEQ ID NO:99).

[0302] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P16 (SEQ ID NO:100), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR corresponding to amino acids 1-397 of SUL1_HUMAN, which also corresponds to amino acids 1-397 of Z21368_PEA.sub.--1_P16 (SEQ ID NO:100), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CVIVPPLSQPQIH (SEQ ID NO:1007) corresponding to amino acids 398-410 of Z21368_PEA.sub.--1_P16 (SEQ ID NO:100), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0303] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P16 (SEQ ID NO:100), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CVIVPPLSQPQIH (SEQ ID NO:1007) in Z21368_PEA.sub.--1-P16 (SEQ ID NO:100).

[0304] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P22 (SEQ ID NO:101), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAK corresponding to amino acids 1-188 of SUL1_HUMAN, which also corresponds to amino acids 1-188 of Z21368_PEA.sub.--1_P22 (SEQ ID NO:101), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO:1008) corresponding to amino acids 189-210 of Z21368_PEA.sub.--1_P22 (SEQ ID NO:101), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0305] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P22 (SEQ ID NO:101), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably, at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO:1008) in Z21368_PEA.sub.--1P22 (SEQ ID NO:101) .

[0306] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1-137 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 1-137 of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH (SEQ ID NO:1009) corresponding to amino acids 138-145 of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0307] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH (SEQ ID NO:1009) in Z21368_PEA.sub.--1_P23 (SEQ ID NO:102).

[0308] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P23 (SEB ID NO:102), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1-137 of SUL1_HUMAN, which also corresponds to amino acids 1-137 of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH (SEQ ID NO:1009) corresponding to amino acids 138-145 of Z21368 PEA.sub.--1_P23 (SEQ ID NO:102), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0309] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH (SEQ ID NO:1009) in Z21368_PEA.sub.--1_P23 (SEQ ID NO:102).

[0310] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P5 (SEO ID NO:143), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 12-55 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-44 of T59832_P5 (SEQ ID NO:143), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG (SEQ ID NO:1010) corresponding to amino acids 45-189 of T59832_P5 (SEQ ID NO:143), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0311] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P5 (SEQ ID NO:143), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00082 VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP (SEQ ID NO: 1010) SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG in T59832_P5. (SEQ ID NO: 143)

[0312] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 12-223 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011 ) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0313] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

[0314] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1-212 of BAC98466 (SEQ ID NO:848), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0315] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

[0316] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYV PWVTVNGVRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 1-148 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0317] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00083 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012) PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P7. (SEQ ID NO: 144)

[0318] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1-212 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0319] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

[0320] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 12-214 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0321] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEO ID NO:145).

[0322] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-203 of BAC98466 (SEQ ID NO:848), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832 P9 (SEO ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0323] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

[0324] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P9 (SEQ ID NO:145), second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-113 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-203 of T59832_P9 (SEQ ID NO:145), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

[0325] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00084 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012) PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P9. (SEQ ID NO: 145)

[0326] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

[0327] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-203 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TABLE-US-00085 (SEQ ID NO: 1013) NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR

corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0328] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEO ID NO:145).

[0329] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 12-141 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-130 of T59832_P12 (SEQ ID NO:146), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173-261 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 131-219 of T59832_P12 (SEQ ID NO:146), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0330] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n-2)-x), in which x varies from 0 to n-2.

[0331] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P12 (SEQ ID NO:146), second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVE corresponding to amino acids 1-40 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-130 of T59832_P12 (SEQ ID NO:146), third amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 72-122 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 131-181 of T59832_P 12 (SEQ ID NO:146), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK (SEQ ID NO:1016) corresponding to amino acids 182-219 of T59832_P12 (SEQ ID NO:146), wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order.

[0332] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T59832_P12 (SEQ ID NO:146), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00086 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012) PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P12. (SEQ ID NO: 146)

[0333] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n-2)-x), in which x varies from 0 to n-2.

[0334] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T59832_P 12 (SEQ ID NO:146), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPS STS SLRSVCFK (SEO ID NO:1016) in T59832_P12 (SEQ IDNO:146).

[0335] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 1-130 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-130 of T59832_P12 (SEQ ID NO:146), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 131-219 of T59832_P12 (SEQ ID NO:146), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0336] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n-2)-x), in which x varies from 0 to n-2.

[0337] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 12-55 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173-261 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0338] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_PI18 (SEQ ID NO:147), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n-2)-x), in which x varies from 0 to n-2.

[0339] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1-44 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0340] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n-2)-x), in which x varies from 0 to n-2.

[0341] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1-44 of Q8NE14 (SEQ ID NO:851), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8NE14 (SEQ ID NO:851), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0342] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n-2)-x), in which x varies from 0 to n-2.

[0343] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMGRP5E-P4 (SEQ ID NO:1566), comprising a first amino acid sequence being at least 90% homologous to MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTG ESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED SSNFKDVGSKGK corresponding to amino acids 1-127 of GRP_HUMAN, which also corresponds to amino acids 1-127 of HUMGRP5E_P4 (SEQ ID NO:156), and a second amino acid sequence being at least 90% homologous to GSQREGRNPQLNQQ corresponding to amino acids 135-148 of GRP_HUMAN, which also corresponds to amino acids 128-141 of HUMGRP5E_P4 (SEQ ID NO:156), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0344] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMGRP5E_P4 (SEQ ID NO:156), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KG, having a structure as follows: a sequence starting from any of amino acid numbers 127-x to 127; and ending at any of amino acid numbers 128 +((n-2)-x), in which x varies from 0 to n-2.

[0345] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMGRP5E_P5 (SEQ ID NO:157), comprising a first amino acid sequence being at least 90% homologous to MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTG ESSSVSERGSLKQQLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSED SSNFKDVGSKGK corresponding to amino acids 1-127 of GRP_HUMAN, which also corresponds to amino acids 1-127 of HUMGRP5E_P5 (SEQ ID NO:157), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DSLLQVLNVKEGTPS (SEQ ID NO:1017) corresponding to amino acids 128-142 of HUMGRP5E_P5 (SEQ ID NO:157), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0346] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMGRP5E_P5 (SEQ ID NO:157), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DSLLQVLNVKEGTPS (SEQ ID NO:1017) in HUMGRP5E_P5 (SEQ ID NO:157).

[0347] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA.sub.--1_P4 (SEQ ID NO:178), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNKPLWARVGDDHLLLLQGEQLRRTT RSVVHPKYHQGSGPILPRRTDEHDLMLLKLARP corresponding to amino acids 1-146 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-146 of AA155578_PEA.sub.--1_P4 (SEQ ID NO:178), and a second amino acid sequence being at least 90% homologous to YNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQGIL SWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 184-276 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 147-239 of AA155578_PEA.sub.--1_P4 (SEQ ID NO:178), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0348] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of AA155578_PEA.sub.--1_P4 (SEQ ID NO:178), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise PY, having a structure as follows: a sequence starting from any of amino acid numbers 146-x to 146; and ending at any of amino acid numbers 147+((n-2)-x), in which x varies from 0 to n-2.

[0349] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA.sub.--1_P6 (SEQ ID NO:179), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1-29 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-29 of AA155578_PEA.sub.--1 P6 (SEQ ID NO:179), and a second amino acid sequence being at least 90 % homologous to VKYNKGLTCSSITILSPKECEVFYPGVVTNNMICAGLDRGQDPCQSDSGGPLVCDETLQ GILSWGVYPCGSAQHPAVYTQICKYMSWINKVIRSN corresponding to amino acids 182-276 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 30-124 of AA155578_PEA.sub.--1_P6 (SEQ ID NO:179), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0350] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of AA155578_PEA.sub.--1_P6 (SEQ ID NO: 179), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise WV, having a structure as follows: a sequence starting from any of amino acid numbers 29-x to 29; and ending at any of amino acid numbers 30+((n-2)-x), in which x varies from 0 to n-2.

[0351] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA.sub.--1_P8 (SEQ ID NO:180), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLW corresponding to amino acids 1-29 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-29 of AA155578_PEA.sub.--1_P8 (SEQ ID NO:180), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GHCGLE (SEQ ID NO:1018) corresponding to amino acids 30-35 of AA155578_PEA.sub.--1_P8 (SEQ ID NO:180), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0352] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of AA155578-PEA.sub.--1_P8 (SEQ ID NO:180), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GHCGLE (SEO ID NO:1018) in AA155578_PEA.sub.--1_P8 (SEQ ID NO:180).

[0353] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA155578_PEA.sub.--1_P9 (SEQ ID NO:181), comprising a first amino acid sequence being at least 90% homologous to MRAPHLHLSAASGARALAKLLPLLMAQLWAAEAALLPQNDTRLDPEAYGAPCARGSQ PWQVSLFNGLSFHCAGVLVDQSWVLTAAHCGNK corresponding to amino acids 1-90 of KLKA_HUMAN (SEQ ID NO:177), which also corresponds to amino acids 1-90 of AA155578_PEA.sub.--1.sub.--P9 (SEQ ID NO:181).

[0354] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSENA78_P2 (SEQ ID NO:919), comprising a first amino acid sequence being at least 90% homologous to MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCVCLQTTQGVHP KMISNLQVFAIGPQCSKVEVV corresponding to amino acids 1-81 of SZ05_HUMAN (SEQ ID NO:190), which also corresponds to amino acids 1-81 of HSENA78_P2 (SEQ ID NO:191) According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T94936_PEA.sub.--1_P2 (SEQ ID NO:206), comprising a first amino acid sequence being at least 90% homologous to MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS KKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFVDPSLTVRADIAGRYSNRLYTYEPRDLPL corresponding to amino acids 1-150 of Q8TD06 (SEQ ID NO:858), which also corresponds to amino acids 1-150 of T94936_PEA.sub.--1_P2 (SEQ ID NO:206).

[0355] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T94936_PEA.sub.--1_P3 (SEQ ID NO:207), comprising a first amino acid sequence being at least 90% homologous to MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKS KKPLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQY VPRIMFV corresponding to amino acids 1-122 of Q8TD06 (SEQ ID NO:858), which also corresponds to amino acids 1-122 of T94936_PEA.sub.--1_P3 (SEQ ID NO:207), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GMYVISFHQIYKISRNQHSCFYF (SEO ID NO:1019) corresponding to amino acids 123-145 of T94936_PEA.sub.--1_P3 (SEQ ID NO:207), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0356] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T94936_PEA.sub.--1_P3 (SEQ ID NO:207), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GMYVISFHQIYKISRNQHSCFYF (SEQ ID NO:1019) in T94936_PEA.sub.--1_P3 (SEQ ID NO:207).

[0357] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), comprising a first amino acid sequence being at least 90% homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 1-95 of SZ14_HUMAN (SEQ ID NO:230), which also corresponds to amino acids 1-95 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) corresponding to amino acids 96-123 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0358] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) in Z41644_PEA.sub.--1-P10 (SEQ ID NO:231).

[0359] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), comprising a first amino acid sequence being at least 90% homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of Q9NS21 (SEQ ID NO:862), which also corresponds to amino acids 1-95 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) corresponding to amino acids 96-123 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0360] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) in Z41644_PEA.sub.--1P10 (SEQ ID NO:231).

[0361] According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), comprising a first amino acid sequence being at least 90% homologous to MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVII TTKSVSRYRGQEHCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of AAQ89265, which also corresponds to amino acids 1-95 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) corresponding to amino acids 96-123 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0362] According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of Z41644_PEA.sub.--1_P10 (SEQ ID NO:231), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO:1020) in Z41644_PEA.sub.--1.sub.--P10(SEQ ID NO:231).

[0363] According to preferred embodiments of the present invention, there is provided an isolated oligonucleotide, comprising an amplicon selected from the group consisting of SEQ ID NOs: 891 or 894.

[0364] According to preferred embodiments of the present invention, there is provided a primer pair, comprising a pair of isolated oligonucleotides capable of amplifying the above. Optionally, the pair of isolated oligonucleotides is selected from the group consisting of: SEQ NOs 889 and 890; or 892 and 893.

[0365] According to preferred embodiments of the present invention, there is provided an antibody capable of specifically binding to an epitope of an amino acid sequence as described herein. Optionally, the epitope may comprise a tail, head, or edge portion as described herein.

[0366] According to preferred embodiments of the present invention, the antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein.

[0367] According to preferred embodiments of the present invention, there is provided an kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant as described herein. Optionally, the kit comprises a NAT-based technology. Preferably, the kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence as described herein. Optionally, the kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence as described herein.

[0368] Optionally, the kit comprises an antibody as described herein. Preferably, the kit further comprises at least one reagent for performing an ELISA or a Western blot.

[0369] According to preferred embodiments of the present invention, there is provided a method for detecting breast cancer, comprising detecting overexpression of a splice variant as described herein.

[0370] Optionally detecting overexpression is performed with a NAT-based technology. Preferably, detecting overexpression is performed with an immunoassay. More preferably, the immunoassay comprises an antibody as described herein.

[0371] According to preferred embodiments of the present invention, there is provided a biomarker capable of detecting breast cancer, comprising any of the above nucleic acid sequences or a fragment thereof, or any of the above amino acid sequences or a fragment thereof.

[0372] According to preferred embodiments of the present invention, preferably any of the above nucleic acid and/or amino acid sequences further comprises any sequence having at least about 70%, preferably at least about 80%, more preferably at least about 90%, most preferably at least about 95% homology thereto.

[0373] Unless otherwise noted, all experimental data relates to variants of the present invention, named according to the segment being tested (as expression was tested through RT-PCR as described).

[0374] All nucleic acid sequences and/or amino acid sequences shown herein as embodiments of the present invention relate to their isolated form, as isolated polynucleotides (including for all transcripts), oligonucleotides (including for all segments, amplicons and primers), peptides (including for all tails, bridges, insertions or heads, optionally including other antibody epitopes as described herein) and/or polypeptides (including for all proteins). It should be noted that oligonucleotide and polynucleotide, or peptide and polypeptide, may optionally be used interchangeably.

[0375] Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this invention belongs. The following references provide one of skill with a general definition of many of the terms used in this invention: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). All of these are hereby incorporated by reference as if fully set forth herein. As used herein, the following terms have the meanings ascribed to them unless specified otherwise.

BRIEF DESCRIPTION OF DRAWINGS

[0376] FIG. 1 is schematic summary of cancer biomarkers selection engine and the wet validation stages.

[0377] FIG. 2. Schematic illustration, depicting grouping of transcripts of a given cluster based on presence or absence of unique sequence regions.

[0378] FIG. 3 is schematic summary of quantitative real-time PCR analysis.

[0379] FIG. 4 is schematic presentation of the oligonucleotide based microarray fabrication.

[0380] FIG. 5 is schematic summary of the oligonucleotide based microarray experimental flow.

[0381] FIG. 6 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T10888, demonstrating overexpression in colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma.

[0382] FIG. 7 is a histogram showing expression of the CEA6_HUMAN (SEQ ID NO:13) Carcinoembryonic antigen-related cell adhesion molecule 6 (T10888) transcripts, which are detectable by amplicon as depicted in sequence name T10888 junc11-17, in normal and cancerous breast tissues.

[0383] FIG. 8 is a histogram showing the expression of CEA6_HUMAN (SEQ ID NO:13) Carcinoembryonic antigen-related cell adhesion molecule 6 T10888 transcripts which are detectable by amplicon as depicted in sequence name T10888junc11-17 (SEQ ID NO:832) in different normal tissues.

[0384] FIG. 9 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T39971, demonstrating overexpression in liver cancer, lung malignant tumors and pancreas carcinoma.

[0385] FIG. 10 is a histogram showing the expression of of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) T39971 transcripts, which are detectable by amplicon as depicted in sequence name T39971 junc23-33 (SEQ ID NO:836) in normal and cancerous breast tissues.

[0386] FIG. 11 is a histogram showing the expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein), antisense to SARM1 (T23434), T39971 transcripts, which are detectable by amplicon as depicted in sequence name T39971junc23-33, in different normal tissues.

[0387] FIG. 12 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster Z21368, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

[0388] FIG. 13 is a histogram showing the expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368seg39 (SEQ ID NO:844), in normal and cancerous breast tissues.

[0389] FIG. 14 is a histogram showing the expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368seg39 (SEQ ID NO:844), in different normal tissues.

[0390] FIG. 15 is a histogram showing the expression of SUL 1_HUMAN--Extracellular sulfatase Sulf-1 Z21368 transcripts which are detectable by amplicon as depicted in sequence name Z21368junc17-21 (SEQ ID NO:847) in normal and cancerous breast tissues.

[0391] FIG. 16 is a histogram showing the expression of SUL 1_HUMAN--Extracellular sulfatase Sulf-1 Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368junc17-21, in different normal tissues.

[0392] FIG. 17 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T59832, demonstrating overexpression in brain malignant tumors, breast malignant tumors, ovarian carcinoma and pancreas carcinoma.

[0393] FIG. 18 is a histogram showing low over expression observed for cluster T59832, amplicon name: T59832 junc6-25-26 (SEQ ID NO:854), in one experiment carried out with breast cancer samples panel.

[0394] FIG. 19 is a histogram showing the expression of GRP_HUMAN--gastrin-releasing peptide (HUMGRP5E) transcripts, which are detectable by amplicon, as depicted insequence name HUMGRP5Ejunc3-7 (SEQ ID NO:857) in normal and cancerous breast tissues.

[0395] FIG. 20 is a histogram showing the expression of GRP_HUMAN--gastrin-releasing peptide (HUMGRP5E) transcripts, which are detectable by amplicon, as depicted in sequence name HUMGRP5Ejunc3-7 (SEQ ID NO:857), in different normal tissues.

[0396] FIG. 21 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster AA155578, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

[0397] FIG. 22 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSENA78, demonstrating overexpression in epithelial malignant tumors and lung malignant tumors.

[0398] FIG. 23 is a histogram showing the expression of Homo sapiens breast cancer membrane protein 11 (BCMP11) T94936 transcripts which are detectable by amplicon as depicted in sequence name T94936 seg14 (SEQ ID NO:861) in normal and cancerous Breast tissues.

[0399] FIG. 24 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster Z41644, demonstrating overexpression in lung malignant tumors, breast malignant tumors and pancreas carcinoma.

[0400] FIG. 25 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster M85491, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues.

[0401] FIG. 26 is a histogram showing the expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 (SEQ ID NO:866) in normal and cancerous breast tissues.

[0402] FIG. 27 is a histogram showing the expression of Ephrin type-B receptor 2 precursor M85491 transcripts,-which are detectable by amplicon as depicted in sequence name M85491 seg24, in different normal tissues.

[0403] FIG. 28 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSSTROL3, demonstrating overexpression in transitional cell carcinoma, epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma.

[0404] FIG. 29A is a histogram showing the expression of Expression of Stromelysin-3 precursor (SEQ ID NO:270) (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) SL-3 HSSTROL3 transcripts which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24 (SEQ ID NO:869) in normal and cancerous breast tissues.

[0405] FIG. 29B is a histogram showing the expression of Stromelysin-3 precursor (SEQ ID NO:270) (EC 3.4.24.-) (Matrix metalloproteinase-11) (MMP-11) (ST3) (SL-3) HSSTROL3 transcripts, which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24 (SEQ ID NO:869), in different normal tissues.

[0406] FIGS. 30A-30C shows histograms showing over expression of various Stromelysin-3 precursor (SEQ ID NO:270) transcripts in cancerous breast samples relative to the normal samples.

[0407] FIG. 31 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster R75793, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues.

[0408] FIG. 32 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HUMCA1XIA, demonstrating overexpression in bone malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors.

[0409] FIG. 33 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster R20779, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors.

[0410] FIG. 34 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSS100PCB, demonstrating overexpression in a mixture of malignant tumors from different tissues.

[0411] FIG. 35 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSCOC4, demonstrating overexpression in brain malignant tumors, a mixture of malignant tumors from different-tissues, breast malignant tumors, pancreas carcinoma and prostate cancer.

[0412] FIG. 36 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HUMTREFAC, demonstrating overexpression in a mixture of malignant tumors from different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer.

[0413] FIG. 37 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HUMOSTRO, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues, lung malignant tumors, breast malignant tumors, ovarian carcinoma and skin malignancies.

[0414] FIG. 38 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster R11723, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and kidney malignant tumors.

[0415] FIG. 39 is a histogram showing the expression of of R11723 transcripts which are detectable by amplicon as depicted in sequence name R11723 seg13 (SEQ ID NO:891) in normal and cancerous breast tissues.

[0416] FIG. 40 is a histogram showing the expression of R11723 transcripts, which are detectable by amplicon as depicted in sequence name R11723seg13 (SEQ ID NO:891), in different normal tissues.

[0417] FIGS. 41A and B are histograms showing the expression of R11723 transcripts, which are detectable by amplicon as depicted in sequence name R11723 junc11-18 (SEQ ID NO:894) in normal and cancerous breast tissues (FIG. 41A) or on a panel of normal tissues (FIG. 41B).

[0418] FIG. 42 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster T46984, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues, breast malignant tumors, ovarian carcinoma and pancreas carcinoma.

[0419] FIG. 43 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSMUC 1A, demonstrating overexpression in a mixture of malignant tumors from different tissues, breast malignant tumors, pancreas carcinoma and prostate cancer.

[0420] FIGS. 44-47 are histograms showing the combined expression of 8 sequences (T10888seg11-17, HUMGR5Ejunc3-7, HSSTROL3seg24, T94936 Seg 14, Z21368 seg39, Z21368junc17-21 T59832jun6-25-26 and M85491seg24 (SEQ ID NO:866)) in normal and cancerous breast tissues.

[0421] FIG. 48 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster HSU33147, demonstrating overexpression in a mixture of malignant tumors from different tissues.

DESCRIPTION OF PREFERRED EMBODIMENTS

[0422] The present invention is of novel markers for breast cancer that are both sensitive and accurate. Furthermore, at least certain of these markers are able to distinguish between different stages of breast cancer, such as 1. Ductal carcinoma (in-situ, invasive) 2. Lobular carcinoma (is-situ, invasive) 3. inflammatory breast cancer 4. Mucinous carcinoma 5. Tubular carcinoma 6. Paget's disease of nipple, alone or in combination; or one of the indicative conditions described above.

[0423] The markers of the present invention, alone or in combination, can be used for prognosis, prediction, screening, early diagnosis, staging, therapy selection and treatment monitoring of breast cancer. For example, optionally and preferably, these markers may be used for staging breast cancer and/or monitoring the progression of the disease. Furthermore, the markers of the present invention, alone or in combination, can be used for detection of the source of metastasis found in anatomical places other then breast. Also, one or more of the markers may optionally be used in combination with one or more other breast cancer markers (other than those described herein).

[0424] Biomolecular sequences (amino acid and/or nucleic acid sequences) uncovered using the methodology of the present invention and described herein can be efficiently utilized as tissue or pathological markers and/or as drugs or drug targets for treating or preventing a disease.

[0425] These markers are specifically released to the bloodstream under conditions of breast cancer (or one of the above indicative conditions), and/or are otherwise expressed at a much higher level and/or specifically expressed in breast cancer tissue or cells, and/or tissue or cells under one of the above indicative conditions. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can correlate with a probable diagnosis of breast cancer and/or a condition that it is indicative of a higher risk for breast cancer.

[0426] The present invention therefore also relates to diagnostic assays for breast cancer and/or an indicative condition, and methods of use of such markers for detection of breast cancer and/or an indicative condition, optionally and preferably in a sample taken from a subject (patient), which is more preferably some type of blood sample.

[0427] According to a preferred embodiment of the present invention, use of the marker optionally and preferably permits a non-cancerous breast disease state to be distinguished from breast cancer and/or an indicative condition. A non limiting example of a non-cancerous breast disease state includes breast fibrosis and/or cysts. According to another preferred embodiment of the present invention, use of the marker optionally and preferably permits an indicative condition to be distinguished from breast cancer.

[0428] In another embodiment, the present invention relates to bridges, tails, heads and/or insertions, and/or analogs, homologs and derivatives of such peptides. Such bridges, tails, heads and/or insertions are described in greater detail below with regard to the Examples.

[0429] As used herein a "tail" refers to a peptide sequence at the end of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice variant having such a tail may optionally be considered as a chimera, in that at least a first portion of the splice variant is typically highly homologous (often 100% identical) to a portion of the corresponding known protein, while at least a second portion of the variant comprises the tail.

[0430] As used herein a "head" refers to a peptide sequence at the beginning of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice variant having such a head may optionally be considered as a chimera, in that at least a first portion of the splice variant comprises the head, while at least a second portion is typically highly homologous (often 100% identical) to a portion of the corresponding known protein.

[0431] As used herein "an edge portion" refers to a connection between two portions of a splice variant according to the present invention that were not joined in the wild type or known protein. An edge may optionally arise due to a join between the above "known protein" portion of a variant and the tail, for example, and/or may occur if an internal portion of the wild type sequence is no longer present, such that two portions of the sequence are now contiguous in the splice variant that were not contiguous in the known protein. A "bridge" may optionally be an edge portion as described above, but may also include a join between a head and a "known protein" portion of a variant, or a join between a tail and a "known protein" portion of a variant, or a join between an insertion and a "known protein" portion of a variant.

[0432] Optionally and preferably, a bridge between a tail or a head or a unique insertion, and a "known protein" portion of a variant, comprises at least about 10 amino acids, more preferably at least about 20 amino acids, most preferably at least about 30 amino acids, and even more preferably at least about 40 amino acids, in which at least one amino acid is from the tail/head/insertion and at least one amino acid is from the "known protein" portion of a variant. Also optionally, the bridge may comprise any number of amino acids from about 10 to about 40 amino acids (for example, 10, 11, 12, 13 . . . 37, 38, 39, 40 amino acids in length, or any number in between).

[0433] It should be noted that a bridge cannot be extended beyond the length of the sequence in either direction, and it should be assumed that every bridge description is to be read in such manner that the bridge length does not extend beyond the sequence itself.

[0434] Furthermore, bridges are described with regard to a sliding window in certain contexts below. For example, certain descriptions of the bridges feature the following format: a bridge between two edges (in which a portion of the known protein is not present in the variant) may optionally be described as follows: a bridge portion of CONTIG-NAME_P1 (representing the name of the protein), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise XX (2 amino acids in the center of the bridge, one from each end of the edge), having a structure as follows (numbering according to the sequence of CONTIG-NAME_P1): a sequence starting from any of amino acid numbers 49-x to 49 (for example); and ending at any of amino acid numbers 50+((n-2)-x) (for example), in which x varies from 0 to n-2. In this example, it should also be read as including bridges in which n is any number of amino acids between 10-50 amino acids in length. Furthermore, the bridge polypeptide cannot extend beyond the sequence, so it should be read such that 49-x (for example) is not less than 1, nor 50+((n-2)-x) (for example) greater than the total sequence length.

[0435] In another embodiment, this invention provides antibodies specifically recognizing the splice variants and polypeptide fragments thereof of this invention. Preferably such antibodies differentially recognize splice variants of the present invention but do not recognize a corresponding known protein (such known proteins are discussed with regard to their splice variants in the Examples below).

[0436] In another embodiment, this invention provides an isolated nucleic acid molecule encoding for a splice variant according to the present invention, having a nucleotide sequence as set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an isolated nucleic acid molecule, having a nucleotide sequence as set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an oligonucleotide of at least about 12 nucleotides, specifically hybridizable with the nucleic acid molecules of this invention. In another embodiment, this invention provides vectors, cells, liposomes and compositions comprising the isolated nucleic acids of this invention.

[0437] In another embodiment, this invention provides a method for detecting a splice variant according to the present invention in a biological sample, comprising: contacting a biological sample with an antibody specifically recognizing a splice variant according to the present invention under conditions whereby the antibody specifically interacts with the splice variant in the biological sample but do not recognize known corresponding proteins (wherein the known protein is discussed with regard to its splice variant(s) in the Examples below), and detecting said interaction; wherein the presence of an interaction correlates with the presence of a splice variant in the biological sample.

[0438] In another embodiment, this invention provides a method for detecting a splice variant nucleic acid sequences in a biological sample, comprising: hybridizing the isolated nucleic acid molecules or oligonucleotide fragments of at least about a minimum length to a nucleic acid material of a biological sample and detecting a hybridization complex; wherein the presence of a hybridization complex correlates with the presence of a splice variant nucleic acid sequence in the biological sample.

[0439] According to the present invention, the splice variants described herein are non-limiting examples of markers for diagnosing breast cancer and/or an indicative condition. Each splice variant marker of the present invention can be used alone or in combination, for various uses, including but not limited to, prognosis, prediction, screening, early diagnosis, determination of progression, therapy selection and treatment monitoring of breast cancer and/or an indicative condition, including a transition from an indicative condition to breast cancer.

[0440] According to optional but preferred embodiments of the present invention, any marker according to the present invention may optionally be used alone or combination. Such a combination may optionally comprise a plurality of markers described herein, optionally including any subcombination of markers, and/or a combination featuring at least one other marker, for example a known marker. Furthermore, such a combination may optionally and preferably be used as described above with regard to determining a ratio between a quantitative or semi-quantitative measurement of any marker described herein to any other marker described herein, and/or any other known marker, and/or any other marker. With regard to such a ratio between any marker described herein (or a combination thereof) and a known marker, more preferably the known marker comprises the "known protein" as described in greater detail below with regard to each cluster or gene.

[0441] According to other preferred embodiments of the present invention, a splice variant protein or a fragment thereof, or a splice variant nucleic acid sequence or a fragment thereof, may be featured as a biomarker for detecting breast cancer and/or an indicative condition, such that a biomarker may optionally comprise any of the above.

[0442] According to still other preferred embodiments, the present invention optionally and preferably encompasses any amino acid sequence or fragment thereof encoded by a nucleic acid sequence corresponding to a splice variant protein as described herein. Any oligopeptide or peptide relating to such an amino acid sequence or fragment thereof may optionally also (additionally or alternatively) be used as a biomarker, including but not limited to the unique amino acid sequences of these proteins that are depicted as tails, heads, insertions, edges or bridges. The present invention also optionally encompasses antibodies capable of recognizing, and/or being elicited by, such oligopeptides or peptides.

[0443] The present invention also optionally and preferably encompasses any nucleic acid sequence or fragment thereof, or amino acid sequence or fragment thereof, corresponding to a splice variant of the present invention as described above, optionally for any application.

[0444] Non-limiting examples of methods or assays are described below.

[0445] The present invention also relates to kits based upon such diagnostic methods or assays.

Nucleic Acid Sequences and Oligonucleotides

[0446] Various embodiments of the present invention encompass nucleic acid sequences described hereinabove; fragments thereof, sequences hybridizable therewith, sequences homologous thereto, sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or more nucleotides, either naturally occurring or artificially induced, either randomly or in a targeted fashion.

[0447] The present invention encompasses nucleic acid sequences described herein; fragments thereof, sequences hybridizable therewith, sequences homologous thereto [e.g., at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, least 95% or more say 100% identical to the nucleic acid sequences set forth below], sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or more nucleotides, either naturally occurring or man induced, either randomly or in a targeted fashion. The present invention also encompasses homologous nucleic acid sequences (i.e., which form a part of a polynucleotide sequence of the present invention) which include sequence regions unique to the polynucleotides of the present invention.

[0448] In cases where the polynucleotide sequences of the present invention encode previously unidentified polypeptides, the present invention also encompasses novel polypeptides or portions thereof, which are encoded by the isolated polynucleotide and respective nucleic acid fragments thereof described hereinabove.

[0449] A "nucleic acid fragment" or an "oligonucleotide" or a "polynucleotide" are used herein interchangeably to refer to a polymer of nucleic acids. A polynucleotide sequence of the present invention refers to a single or double stranded nucleic acid sequences which is isolated and provided in the form of an RNA sequence, a complementary polynucleotide sequence (cDNA), a genomic polynucleotide sequence and/or a composite polynucleotide sequences (e.g., a combination of the above).

[0450] As used herein the phrase "complementary polynucleotide sequence" refers to a sequence, which results from reverse transcription of messenger RNA using a reverse transcriptase or any other RNA dependent DNA polymerase. Such a sequence can be subsequently amplified in vivo or in vitro using a DNA dependent DNA polymerase.

[0451] As used herein the phrase "genomic polynucleotide sequence" refers to a sequence derived (isolated) from a chromosome and thus it represents a contiguous portion of a chromosome.

[0452] As used herein the phrase "composite polynucleotide sequence" refers to a sequence, which is composed of genomic and cDNA sequences. A composite sequence can include some exonal sequences required to encode the polypeptide of the present invention, as well as some intronic sequences interposing therebetween. The intronic sequences can be of any source, including of other genes, and typically will include conserved splicing signal sequences. Such intronic sequences may further include cis acting expression regulatory elements.

[0453] Preferred embodiments of the present invention encompass oligonucleotide probes.

[0454] An example of an oligonucleotide probe which can be utilized by the present invention is a single stranded polynucleotide which includes a sequence complementary to the unique sequence region of any variant according to the present invention, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein).

[0455] Alternatively, an oligonucleotide probe of the present invention can be designed to hybridize with a nucleic acid sequence encompassed by any of the above nucleic acid sequences, particularly the portions specified above, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein).

[0456] Oligonucleotides designed according to the teachings of the present invention can be generated according to any oligonucleotide synthesis method known in the art such as enzymatic synthesis or solid phase synthesis. Equipment and reagents for executing solid-phase synthesis are commercially available from, for example, Applied Biosystems. Any other means for such synthesis may also be employed; the actual synthesis of the oligonucleotides is well within the capabilities of one skilled in the art and can be accomplished via established methodologies as detailed in, for example, "Molecular Cloning: A laboratory Manual" Sambrook et al., (1989); "Current Protocols in Molecular Biology" Volumes 1-111 Ausubel, R. M., ed. (1994); Ausubel et al., "Current Protocols in Molecular Biology", John Wiley and Sons, Baltimore, Md. (1989); Perbal, "A Practical Guide to Molecular Cloning", John Wiley & Sons, New York (1988) and "Oligonucleotide Synthesis" Gait, M. J., ed. (1984) utilizing solid phase chemistry, e.g. cyanoethyl phosphoramidite followed by deprotection, desalting and purification by for example, an automated trityl-on method or HPLC.

[0457] Oligonucleotides used according to this aspect of the present invention are those having a length selected from a range of about 10 to about 200 bases preferably about 15 to about 150 bases, more preferably about 20 to about 100 bases, most preferably about 20 to about 50 bases. Preferably, the oligonucleotide of the present invention features at least 17, at least 18, at least 19, at least 20, at least 22, at least 25, at least 30 or at least 40, bases specifically hybridizable with the biomarkers of the present invention.

[0458] The oligonucleotides of the present invention may comprise heterocylic nucleosides consisting of purines and the pyrimidines bases, bonded in a 3' to 5' phosphodiester linkage.

[0459] Preferably used oligonucleotides are those modified at one or more of the backbone, internucleoside linkages or bases, as is broadly described hereinunder.

[0460] Specific examples of preferred oligonucleotides useful according to this aspect of the present invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages. Oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone, as disclosed in U.S. Pat. Nos: 4,469,863; 4,476,301; 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466, 677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625,050.

[0461] Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkyl phosphotriesters, methyl and other alkyl phosphonates including 3'-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3'-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'. Various salts, mixed salts and free acid for also be used.

[0462] Alternatively, modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH.sub.2 component parts, as disclosed in U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439.

[0463] Other oligonucleotides which can be used according to the present invention, are those modified in both sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for complementation with the appropriate polynucleotide target. An example for such an oligonucleotide mimetic, includes peptide nucleic acid (PNA). U.S. patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Other backbone modifications, which can be used in the present invention are disclosed in U.S. Pat. No: 6,303,374.

[0464] Oligonucleotides of the present invention may also include base modifications or substitutions. As used herein, "unmodified" or "natural" bases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified bases include but are not limited to other synthetic and natural bases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine. Further bases particularly useful for increasing the binding affinity of the oligomeric compounds of the invention include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2.degree. C. and are presently preferred base substitutions, even more particularly when combined with 2'-O-methoxyethyl sugar modifications.

[0465] Another modification of the oligonucleotides of the invention involves chemically linking to the oligonucleotide one or more moieties or conjugates, which enhance the activity, cellular distribution or cellular uptake of the oligonucleotide. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety, cholic acid, a thioether, e.g., hexyl-S-tritylthiol, a thiocholesterol, an aliphatic chain, e.g., dodecandiol or undecyl residues, a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate, a polyamine or a polyethylene glycol chain, or adamantane acetic acid, a palmityl moiety, or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety, as disclosed in U.S. Pat. No: 6,303,374.

[0466] It is not necessary for all positions in a given oligonucleotide molecule to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an oligonucleotide.

[0467] It will be appreciated that oligonucleotides of the present invention may include further modifications for more efficient use as diagnostic agents and/or to increase bioavailability, therapeutic efficacy and reduce cytotoxicity.

[0468] To enable cellular expression of the polynucleotides of the present invention, a nucleic acid construct according to the present invention may be used, which includes at least a coding region of one of the above nucleic acid sequences, and further includes at least one cis acting regulatory element. As used herein, the phrase "cis acting regulatory element" refers to a polynucleotide sequence, preferably a promoter, which binds a trans acting regulator and regulates the transcription of a coding sequence located downstream thereto.

[0469] Any suitable promoter sequence can be used by the nucleic acid construct of the present invention.

[0470] Preferably, the promoter utilized by the nucleic acid construct of the present invention is active in the specific cell population transformed. Examples of cell type-specific and/or tissue-specific promoters include promoters such as albumin that is liver specific, lymphoid specific promoters [Calame et al., (1988) Adv. Immunol. 43:235-275]; in particular promoters of T-cell receptors [Winoto et al., (1989) EMBO J. 8:729-733] and immunoglobulins; [Banerji et al. (1983) Cell 33729-740], neuron-specific promoters such as the neurofilament promoter [Byrne et al. (1989) Proc. Natl. Acad. Sci. USA 86:5473-5477], pancreas-specific promoters [Edlunch et al. (1985) Science 230:912-916] or mammary gland-specific promoters such as the milk whey promoter (U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). The nucleic acid construct of the present invention can further include an enhancer, which can be adjacent or distant to the promoter sequence and can function in up regulating the transcription therefrom.

[0471] The nucleic acid construct of the present invention preferably further includes an appropriate selectable marker and/or an origin of replication. Preferably, the nucleic acid construct utilized is a shuttle vector, which can propagate both in E. coli (wherein the construct comprises an appropriate selectable marker and origin of replication) and be compatible for propagation in cells, or integration in a gene and a tissue of choice. The construct according to the present invention can be, for example, a plasmid, a bacmid, a phagemid, a cosmid, a phage, a virus or an artificial chromosome.

[0472] Examples of suitable constructs include, but are not limited to, pcDNA3, pcDNA3.1 (.+-.), pGL3, PzeoSV2 (.+-.), pDisplay, pEF/myc/cyto, pCMV/myc/cyto each of which is commercially available from Invitrogen Co. (www.invitrogen.com). Examples of retroviral vector and packaging systems are those sold by Clontech, San Diego, Calif., including Retro-X vectors pLNCX and pLXSN, which permit cloning into multiple cloning sites and the trasgene is transcribed from CMV promoter. Vectors derived from Mo-MuLV are also included such as pBabe, where the transgene will be transcribed from the 5'LTR promoter.

[0473] Currently preferred in vivo nucleic acid transfer techniques include transfection with viral or non-viral constructs, such as adenovirus, lentivirus, Herpes simplex I virus, or adeno-associated virus (AAV) and lipid-based systems. Useful lipids for lipid-mediated transfer of the gene are, for example, DOTMA, DOPE, and DC-Chol [Tonkinson et al., Cancer Investigation, 14(1): 54-65 (1996)]. The most preferred constructs for use in gene therapy are viruses, most preferably adenoviruses, AAV, lentiviruses, or retroviruses. A viral construct such as a retroviral construct includes at least one transcriptional promoter/enhancer or locus-defining element(s), or other elements that control gene expression by other means such as alternate splicing, nuclear RNA export, or post-translational modification of messenger. Such vector constructs also include a packaging signal, long terminal repeats (LTRs) or portions thereof, and positive and negative strand primer binding sites appropriate to the virus used, unless it is already present in the viral construct. In addition, such a construct typically includes a signal sequence for secretion of the peptide from a host cell in which it is placed. Preferably the signal sequence for this purpose is a mammalian signal sequence or the signal sequence of the polypeptide variants of the present invention. Optionally, the construct may also include a signal that directs polyadenylation, as well as one or more restriction sites and a translation termination sequence. By way of example, such constructs will typically include a 5' LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3' LTR or a portion thereof. Other vectors can be used that are non-viral, such as cationic lipids, polylysine, and dendrimers.

Hybridization Assays

[0474] Detection of a nucleic acid of interest in a biological sample may optionally be effected by hybridization-based assays using an oligonucleotide probe (non-limiting examples of probes according to the present invention were previously described).

[0475] Traditional hybridization assays include PCR, RT-PCR, Real-time PCR, RNase protection, in-situ hybridization, primer extension, Southern blots (DNA detection), dot or slot blots (DNA, RNA), and Northern blots (RNA detection) (NAT type assays are described in greater detail below). More recently, PNAs have been described (Nielsen et al. 1999, Current Opin. Biotechnol. 10:71-75). Other detection methods include kits containing probes on a dipstick setup and the like.

[0476] Hybridization based assays which allow the detection of a variant of interest (i.e., DNA or RNA) in a biological sample rely on the use of oligonucleotides which can be 10, 15, 20, or 30 to 100 nucleotides long preferably from 10 to 50, more preferably from 40 to 50 nucleotides long.

[0477] Thus, the isolated polynucleotides (oligonucleotides) of the present invention are preferably hybridizable with any of the herein described nucleic acid sequences under moderate to stringent hybridization conditions.

[0478] Moderate to stringent hybridization conditions are characterized by a hybridization solution such as containing 10% dextrane sulfate, 1 M NaCl, 1% SDS and 5.times.10.sup.6 cpm .sup.32P labeled probe, at 65.degree. C., with a final wash solution of 0.2.times.SSC and 0.1% SDS and final wash at 65.degree. C and whereas moderate hybridization is effected using a hybridization solution containing 10% dextrane sulfate, 1 M NaCl, 1% SDS and 5.times.10.sup.6 cpm .sup.32p labeled probe, at 65.degree. C, with a final wash solution of 1.times.SSC and 0.1% SDS and final wash at 50.degree. C.

[0479] More generally, hybridization of short nucleic acids (below 200 bp in length, e.g. 17-40 bp in length) can be effected using the following exemplary hybridization protocols which can be modified according to the desired stringency; (i) hybridization solution of 6.times.SSC and 1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 .mu.g/ml denatured salmon sperm DNA and 0.1% nonfat dried milk, hybridization temperature of 1-1.5.degree. C. below the T.sub.m, final wash solution of 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS at 1-1.5.degree. C. below the T.sub.m; (ii) hybridization solution of 6.times.SSC and 0.1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 .mu.g/ml denatured salmon sperm DNA and 0.1% nonfat dried milk, hybridization temperature of 2-2.5.degree. C. below the T.sub.m, final wash solution of 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS at 1-1.5.degree. C. below the T.sub.m, final wash solution of 6.times.SSC, and final wash at 22.degree. C.; (iii) hybridization solution of 6.times.SSC and 1% SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 .mu.g/ml denatured salmon sperm DNA and 0.1% nonfat dried milk, hybridization temperature.

[0480] The detection of hybrid duplexes can be carried out by a number of methods. Typically, hybridization duplexes are separated from unhybridized nucleic acids and the labels bound to the duplexes are then detected. Such labels refer to radioactive, fluorescent, biological or enzymatic tags or labels of standard use in the art. A label can be conjugated to either the oligonucleotide probes or the nucleic acids derived from the biological sample.

[0481] Probes can be labeled according to numerous well known methods. Non-limiting examples of radioactive labels include 3H, 14C, 32P, and 35S. Non-limiting examples of detectable markers include ligands, fluorophores, chemiluminescent agents, enzymes, and antibodies. Other detectable markers for use with probes, which can enable an increase in sensitivity of the method of the invention, include biotin and radio-nucleotides. It will become evident to the person of ordinary skill that the choice of a particular label dictates the manner in which it is bound to the probe.

[0482] For example, oligonucleotides of the present invention can be labeled subsequent to synthesis, by incorporating biotinylated dNTPs or rNTP, or some similar means (e.g., photo-cross-linking a psoralen derivative of biotin to RNAs), followed by addition of labeled streptavidin (e.g., phycoerythrin-conjugated streptavidin) or the equivalent. Alternatively, when fluorescently-labeled oligonucleotide probes are used, fluorescein, lissamine, phycoerythrin, rhodamine (Perkin Elmer Cetus), Cy2, Cy3, Cy3.5, Cy5, Cy5.5, Cy7, FluorX (Amersham) and others [e.g., Kricka et al. (1992), Academic Press San Diego, Calif.] can be attached to the oligonucleotides.

[0483] Those skilled in the art will appreciate that wash steps may be employed to wash away excess target DNA or probe as well as unbound conjugate. Further, standard heterogeneous assay formats are suitable for detecting the hybrids using the labels present on the oligonucleotide primers and probes.

[0484] It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays. For instance, samples may be hybridized to an irrelevant probe and treated with RNAse A prior to hybridization, to assess false hybridization.

[0485] Although the present invention is not specifically dependent on the use of a label for the detection of a particular nucleic acid sequence, such a label might be beneficial, by increasing the sensitivity of the detection. Furthermore, it enables automation. Probes can be labeled according to numerous well known methods.

[0486] As commonly known, radioactive nucleotides can be incorporated into probes of the invention by several methods. Non-limiting examples of radioactive labels include .sup.3H, .sup.14C, .sup.32P, and .sup.35S.

[0487] Those skilled in the art will appreciate that wash steps may be employed to wash away excess target DNA or probe as well as unbound conjugate. Further, standard heterogeneous assay formats are suitable for detecting the hybrids using the labels present on the oligonucleotide primers and probes.

[0488] It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays.

[0489] Probes of the invention can be utilized with naturally occurring sugar-phosphate backbones as well as modified backbones including phosphorothioates, dithionates, alkyl phosphonates and a-nucleotides and the like. Probes of the invention can be constructed of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and preferably of DNA.

NAT Assays

[0490] Detection of a nucleic acid of interest in a biological sample may also optionally be effected by NAT-based assays, which involve nucleic acid amplification technology, such as PCR for example (or variations thereof such as real-time PCR for example).

[0491] As used herein, a "primer" defines an oligonucleotide which is capable of annealing to (hybridizing with) a target sequence, thereby creating a double stranded region which can serve as an initiation point for DNA synthesis under suitable conditions.

[0492] Amplification of a selected, or target, nucleic acid sequence may be carried out by a number of suitable methods. See generally Kwoh et al., 1990, Am. Biotechnol. Lab. 8:14 Numerous amplification techniques have been described and can be readily adapted to suit particular needs of a person of ordinary skill. Non-limiting examples of amplification techniques include polymerase chain reaction (PCR), ligase chain reaction (LCR), strand displacement amplification (SDA), transcription-based amplification, the q3 replicase system and NASBA (Kwoh et al., 1989, Proc. NatI. Acad. Sci. USA 86, 1173-1177; Lizardi et al., 1988, BioTechnology 6:1197-1202; Malek et al., 1994, Methods Mol. Biol., 28:253-260; and Sambrook et al., 1989, supra).

[0493] The terminology "amplification pair" (or "primer pair") refers herein to a pair of oligonucleotides (oligos) of the present invention, which are selected to be used together in amplifying a selected nucleic acid sequence by one of a number of types of amplification processes, preferably a polymerase chain reaction. Other types of amplification processes include ligase chain reaction, strand displacement amplification, or nucleic acid sequence-based amplification, as explained in greater detail below. As commonly known in the art, the oligos are designed to bind to a complementary sequence under selected conditions.

[0494] In one particular embodiment, amplification of a nucleic acid sample from a patient is amplified under conditions which favor the amplification of the most abundant differentially expressed nucleic acid. In one preferred embodiment, RT-PCR is carried out on an mRNA sample from a patient under conditions which favor the amplification of the most abundant mRNA. In another preferred embodiment, the amplification of the differentially expressed nucleic acids is carried out simultaneously. It will be realized by a person skilled in the art that such methods could be adapted for the detection of differentially expressed proteins instead of differentially expressed nucleic acid sequences.

[0495] The nucleic acid (i.e. DNA or RNA) for practicing the present invention may be obtained according to well known methods.

[0496] Oligonucleotide primers of the present invention may be of any suitable length, depending on the particular assay format and the particular needs and targeted genomes employed. Optionally, the oligonucleotide primers are at least 12 nucleotides in length, preferably between 15 and 24 molecules, and they may be adapted to be especially suited to a chosen nucleic acid amplification system. As commonly known in the art, the oligonucleotide primers can be designed by taking into consideration the melting point of hybridization thereof with its targeted sequence (Sambrook et al., 1989, Molecular Cloning--A Laboratory Manual, 2nd Edition, CSH Laboratories; Ausubel et al., 1989, in Current Protocols in Molecular Biology, John Wiley & Sons Inc., N.Y.).

[0497] It will be appreciated that antisense oligonucleotides may be employed to quantify expression of a splice isoform of interest. Such detection is effected at the pre-mRNA level. Essentially the ability to quantitate transcription from a splice site of interest can be effected based on splice site accessibility. Oligonucleotides may compete with splicing factors for the splice site sequences. Thus, low activity of the antisense oligonucleotide is indicative of splicing activity.

[0498] The polymerase chain reaction and other nucleic acid amplification reactions are well known in the art (various non-limiting examples of these reactions are described in greater detail below). The pair of oligonucleotides according to this aspect of the present invention are preferably selected to have compatible melting temperatures (Tm), e.g., melting temperatures which differ by less than that 7.degree. C., preferably less than 5.degree. C., more preferably less than 4.degree. C., most preferably less than 3.degree. C., ideally between 3.degree. C. and 0.degree. C.

[0499] Polymerase Chain Reaction (PCR): The polymerase chain reaction (PCR), as described in U.S. Pat. Nos. 4,683,195 and 4,683,202 to Mullis and Mullis et al., is a method of increasing the concentration of a segment of target sequence in a mixture of genomic DNA without cloning or purification. This technology provides one approach to the problems of low target sequence concentration. PCR can be used to directly increase the concentration of the target to an easily detectable level. This process for amplifying the target sequence involves the introduction of a molar excess of two oligonucleotide primers which are complementary to their respective strands of the double-stranded target sequence to the DNA mixture containing the desired target sequence. The mixture is denatured and then allowed to hybridize. Following hybridization, the primers are extended with polymerase so as to form complementary strands. The steps of denaturation, hybridization (annealing), and polymerase extension (elongation) can be repeated as often as needed, in order to obtain relatively high concentrations of a segment of the desired target sequence.

[0500] The length of the segment of the desired target sequence is determined by the relative positions of the primers with respect to each other, and, therefore, this length is a controllable parameter. Because the desired segments of the target sequence become the dominant sequences (in terms of concentration) in the mixture, they are said to be "PCR-amplified."

[0501] Ligase Chain Reaction (LCR or LAR): The ligase chain reaction [LCR; sometimes referred to as "Ligase Amplification Reaction" (LAR)] has developed into a well-recognized alternative method of amplifying nucleic acids. In LCR, four oligonucleotides, two adjacent oligonucleotides which uniquely hybridize to one strand of target DNA, and a complementary set of adjacent oligonucleotides, which hybridize to the opposite strand are mixed and DNA ligase is added to the mixture. Provided that there is complete complementarity at the junction, ligase will covalently link each set of hybridized molecules. Importantly, in LCR, two probes are ligated together only when they base-pair with sequences in the target sample, without gaps or mismatches. Repeated cycles of denaturation, and ligation amplify a short segment of DNA. LCR has also been used in combination with PCR to achieve enhanced detection of single-base changes: see for example Segev, PCT Publication No. W09001069 A1 (1990). However, because the four oligonucleotides used in this assay can pair to form two short ligatable fragments, there is the potential for the generation of target-independent background signal. The use of LCR for mutant screening is limited to the examination of specific nucleic acid positions.

[0502] Self-Sustained Synthetic Reaction (3SR/NASBA): The self-sustained sequence replication reaction (3SR) is a transcription-based in vitro amplification system that can exponentially amplify RNA sequences at a uniform temperature. The amplified RNA can then be utilized for mutation detection. In this method, an oligonucleotide primer is used to add a phage RNA polymerase promoter to the 5' end of the sequence of interest. In a cocktail of enzymes and substrates that includes a second primer, reverse transcriptase, RNase H, RNA polymerase and ribo-and deoxyribonucleoside triphosphates, the target sequence undergoes repeated rounds of transcription, cDNA synthesis and second-strand synthesis to amplify the area of interest. The use of 3SR to detect mutations is kinetically limited to screening small segments of DNA (e.g., 200-300 base pairs).

[0503] Q-Beta (Q.beta.) Replicase: In this method, a probe which recognizes the sequence of interest is attached to the replicatable RNA template for Q.beta. replicase. A previously identified major problem with false positives resulting from the replication of unhybridized probes has been addressed through use of a sequence-specific ligation step. However, available thermostable DNA ligases are not effective on this RNA substrate, so the ligation must be performed by T4 DNA ligase at low temperatures (37 degrees C.). This prevents the use of high temperature as a means of achieving specificity as in the LCR, the ligation event can be used to detect a mutation at the junction site, but not elsewhere.

[0504] A successful diagnostic method must be very specific. A straight-forward method of controlling the specificity of nucleic acid hybridization is by controlling the temperature of the reaction. While the 3SR/NASBA, and Q.beta. systems are all able to generate a large quantity of signal, one or more of the enzymes involved in each cannot be used at high temperature (i.e., >55 degrees C). Therefore the reaction temperatures cannot be raised to prevent non-specific hybridization of the probes. If probes are shortened in order to make them melt more easily at low temperatures, the likelihood of having more than one perfect match in a complex genome increases. For these reasons, PCR and LCR currently dominate the research field in detection technologies.

[0505] The basis of the amplification procedure in the PCR and LCR is the fact that the products of one cycle become usable templates in all subsequent cycles, consequently doubling the population with each cycle. The final yield of any such doubling system can be expressed as: (1+X).sup.n=y, where "X" is the mean efficiency (percent copied in each cycle), "n" is the number of cycles, and "y" is the overall efficiency, or yield of the reaction. If every copy of a target DNA is utilized as a template in every cycle of a polymerase chain reaction, then the mean efficiency is 100%. If 20 cycles of PCR are performed, then the yield will be 2.sup.20, or 1,048,576 copies of the starting material. If the reaction conditions reduce the mean efficiency to 85%, then the yield in those 20 cycles will be only 1.85.sup.20, or 220,513 copies of the starting material. In other words, a PCR running at 85% efficiency will yield only 21% as much final product, compared to a reaction running at 100% efficiency. A reaction that is reduced to 50% mean efficiency will yield less than 1% of the possible product.

[0506] In practice, routine polymerase chain reactions rarely achieve the theoretical maximum yield, and PCRs are usually run for more than 20 cycles to compensate for the lower yield. At 50% mean efficiency, it would take 34 cycles to achieve the million-fold amplification theoretically possible in 20, and at lower efficiencies, the number of cycles required becomes prohibitive. In addition, any background products that amplify with a better mean efficiency than the intended target will become the dominant products.

[0507] Also, many variables can influence the mean efficiency of PCR, including target DNA length and secondary structure, primer length and design, primer and dNTP concentrations, and buffer composition, to name but a few. Contamination of the reaction with exogenous DNA (e.g., DNA spilled onto lab surfaces) or cross-contamination is also a major consideration. Reaction conditions must be carefully optimized for each different primer pair and target sequence, and the process can take days, even for an experienced investigator. The laboriousness of this process, including numerous technical considerations and other factors, presents a significant drawback to using PCR in the clinical setting. Indeed, PCR has yet to penetrate the clinical market in a significant way. The same concerns arise with LCR, as LCR must also be optimized to use different oligonucleotide sequences for each target sequence. In addition, both methods require expensive equipment, capable of precise temperature cycling.

[0508] Many applications of nucleic acid detection technologies, such as in studies of allelic variation, involve not only detection of a specific sequence in a complex background, but also the discrimination between sequences with few, or single, nucleotide differences. One method of the detection of allele-specific variants by PCR is based upon the fact that it is difficult for Taq polymerase to synthesize a DNA strand when there is a mismatch between the template strand and the 3' end of the primer. An allele-specific variant may be detected by the use of a primer that is perfectly matched with only one of the possible alleles; the mismatch to the other allele acts to prevent the extension of the primer, thereby preventing the amplification of that sequence. This method has a substantial limitation in that the base composition of the mismatch influences the ability to prevent extension across the mismatch, and certain mismatches do not prevent extension or have only a minimal effect.

[0509] A similar 3'-mismatch strategy is used with greater effect to prevent ligation in the LCR. Any mismatch effectively blocks the action of the thermostable ligase, but LCR still has the drawback of target-independent background ligation products initiating the amplification. Moreover, the combination of PCR with subsequent LCR to identify the nucleotides at individual positions is also a clearly cumbersome proposition for the clinical laboratory.

[0510] The direct detection method according to various preferred embodiments of the present invention may be, for example a cycling probe reaction (CPR) or a branched DNA analysis.

[0511] When a sufficient amount of a nucleic acid to be detected is available, there are advantages to detecting that sequence directly, instead of making more copies of that target, (e.g., as in PCR and LCR). Most notably, a method that does not amplify the signal exponentially is more amenable to quantitative analysis. Even if the signal is enhanced by attaching multiple dyes to a single oligonucleotide, the correlation between the final signal intensity and amount of target is direct. Such a system has an additional advantage that the products of the reaction will not themselves promote further reaction, so contamination of lab surfaces by the products is not as much of a concern. Recently devised techniques have sought to eliminate the use of radioactivity and/or improve the sensitivity in automatable formats. Two examples are the "Cycling Probe Reaction" (CPR), and "Branched DNA" (bDNA).

[0512] Cycling probe reaction (CPR): The cycling probe reaction (CPR), uses a long chimeric oligonucleotide in which a central portion is made of RNA while the two termini are made of DNA. Hybridization of the probe to a target DNA and exposure to a thermostable RNase H causes the RNA portion to be digested. This destabilizes the remaining DNA portions of the duplex, releasing the remainder of the probe from the target DNA and allowing another probe molecule to repeat the process. The signal, in the form of cleaved probe molecules, accumulates at a linear rate. While the repeating process increases the signal, the RNA portion of the oligonucleotide is vulnerable to RNases that may carried through sample preparation.

[0513] Branched DNA: Branched DNA (bDNA), involves oligonucleotides with branched structures that allow each individual oligonucleotide to carry 35 to 40 labels (e.g., alkaline phosphatase enzymes). While this enhances the signal from a hybridization event, signal from non-specific binding is similarly increased.

[0514] The detection of at least one sequence change according to various preferred embodiments of the present invention may be accomplished by, for example restriction fragment length polymorphism (RFLP analysis), allele specific oligonucleotide (ASO) analysis, Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE), Single-Strand Conformation Polymorphism (SSCP) analysis or Dideoxy fingerprinting (ddF).

[0515] The demand for tests which allow the detection of specific nucleic acid sequences and sequence changes is growing rapidly in clinical diagnostics. As nucleic acid sequence data for genes from humans and pathogenic organisms accumulates, the demand for fast, cost-effective, and easy-to-use tests for as yet mutations within specific sequences is rapidly increasing.

[0516] A handful of methods have been devised to scan nucleic acid segments for mutations. One option is to determine the entire gene sequence of each test sample (e.g., a bacterial isolate). For sequences under approximately 600 nucleotides, this may be accomplished using amplified material (e.g., PCR reaction products). This avoids the time and expense associated with cloning the segment of interest. However, specialized equipment and highly trained personnel are required, and the method is too labor-intense and expensive to be practical and effective in the clinical setting.

[0517] In view of the difficulties associated with sequencing, a given segment of nucleic acid may be characterized on several other levels. At the lowest resolution, the size of the molecule can be determined by electrophoresis by comparison to a known standard run on the same gel. A more detailed picture of the molecule may be achieved by cleavage with combinations of restriction enzymes prior to electrophoresis, to allow construction of an ordered map. The presence of specific sequences within the fragment can be detected by hybridization of a labeled probe, or the precise nucleotide sequence can be determined by partial chemical degradation or by primer extension in the presence of chain-terminating nucleotide analogs.

[0518] Restriction fragment length polymorphism (RFLP): For detection of single-base differences between like sequences, the requirements of the analysis are often at the highest level of resolution. For cases in which the position of the nucleotide in question is known in advance, several methods have been developed for examining single base changes without direct sequencing. For example, if a mutation of interest happens to fall within a restriction recognition sequence, a change in the pattern of digestion can be used as a diagnostic tool (e.g., restriction fragment length polymorphism [RFLP] analysis).

[0519] Single point mutations have been also detected by the creation or destruction of RFLPs. Mutations are detected and localized by the presence and size of the RNA fragments generated by cleavage at the mismatches. Single nucleotide mismatches in DNA heteroduplexes are also recognized and cleaved by some chemicals, providing an alternative strategy to detect single base substitutions, generically named the "Mismatch Chemical Cleavage" (MCC). However, this method requires the use of osmium tetroxide and piperidine, two highly noxious chemicals which are not suited for use in a clinical laboratory.

[0520] RFLP analysis suffers from low sensitivity and requires a large amount of sample. When RFLP analysis is used for the detection of point mutations, it is, by its nature, limited to the detection of only those single base changes which fall within a restriction sequence of a known restriction endonuclease. Moreover, the majority of the available enzymes have 4 to 6 base-pair recognition sequences, and cleave too frequently for many large-scale DNA manipulations. Thus, it is applicable only in a small fraction of cases, as most mutations do not fall within such sites.

[0521] A handful of rare-cutting restriction enzymes with 8 base-pair specificities have been isolated and these are widely used in genetic mapping, but these enzymes are few in number, are limited to the recognition of G+C-rich sequences, and cleave at sites that tend to be highly clustered. Recently, endonucleases encoded by group I introns have been discovered that might have greater than 12 base-pair specificity, but again, these are few in number.

[0522] Allele specific oligonucleotide (ASO): If the change is not in a recognition sequence, then allele-specific oligonucleotides (ASOs), can be designed to hybridize in proximity to the mutated nucleotide, such that a primer extension or ligation event can bused as the indicator of a match or a mis-match. Hybridization with radioactively labeled allelic specific oligonucleotides (ASO) also has been applied to the detection of specific point mutations. The method is based on the differences in the melting temperature of short DNA fragments differing by a single nucleotide. Stringent hybridization and washing conditions can differentiate between mutant and wild-type alleles. The ASO approach applied to PCR products also has been extensively utilized by various researchers to detect and characterize point mutations in ras genes and gsp/gip oncogenes. Because of the presence of various nucleotide changes in multiple positions, the ASO method requires the use of many oligonucleotides to cover all possible oncogenic mutations.

[0523] With either of the techniques described above (i.e., RFLP and ASO), the precise location of the suspected mutation must be known in advance of the test. That is to say, they are inapplicable when one needs to detect the presence of a mutation within a gene or sequence of interest.

[0524] Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE): Two other methods rely on detecting changes in electrophoretic mobility in response to minor sequence changes. One of these methods, termed "Denaturing Gradient Gel Electrophoresis" (DGGE) is based on the observation that slightly different sequences will display different patterns of local melting when electrophoretically resolved on a gradient gel. In this manner, variants can be distinguished, as differences in melting properties of homoduplexes versus heteroduplexes differing in a single nucleotide can detect the presence of mutations in the target sequences because of the corresponding changes in their electrophoretic mobilities. The fragments to be analyzed, usually PCR products, are "clamped" at one end by a long stretch of G-C base pairs (30-80) to allow complete denaturation of the sequence of interest without complete dissociation of the strands. The attachment of a GC "clamp" to the DNA fragments increases the fraction of mutations that can be recognized by DGGE. Attaching a GC clamp to one primer is critical to ensure that the amplified sequence has a low dissociation temperature. Modifications of the technique have been developed, using temperature gradients, and the method can be also applied to RNA:RNA duplexes.

[0525] Limitations on the utility of DGGE include the requirement that the denaturing conditions must be optimized for each type of DNA to be tested. Furthermore, the method requires specialized equipment to prepare the gels and maintain the needed high temperatures during electrophoresis. The expense associated with the synthesis of the clamping tail on one oligonucleotide for each sequence to be tested is also a major consideration. In addition, long running times are required for DGGE. The long running time of DGGE was shortened in a modification of DGGE called constant denaturant gel electrophoresis (CDGE). CDGE requires that gels be performed under different denaturant conditions in order to reach high efficiency for the detection of mutations.

[0526] A technique analogous to DGGE, termed temperature gradient gel electrophoresis (TGGE), uses a thermal gradient rather than a chemical denaturant gradient. TGGE requires the use of specialized equipment which can generate a temperature gradient perpendicularly oriented relative to the electrical field. TGGE can detect mutations in relatively small fragments of DNA therefore scanning of large gene segments requires the use of multiple PCR products prior to running the gel.

[0527] Single-Strand Conformation Polymorphism (SSCP): Another common method, called "Single-Strand Conformation Polymorphism" (SSCP) was developed by Hayashi, Sekya and colleagues and is based on the observation that single strands of nucleic acid can take on characteristic conformations in non-denaturing conditions, and these conformations influence electrophoretic mobility. The complementary strands assume sufficiently different structures that one strand may be resolved from the other. Changes in sequences within the fragment will also change the conformation, consequently altering the mobility and allowing this to be used as an assay for sequence variations.

[0528] The SSCP process involves denaturing a DNA segment (e.g., a PCR product) that is labeled on both strands, followed by slow electrophoretic separation on a non-denaturing polyacrylamide gel, so that intra-molecular interactions can form and not be disturbed during the run. This technique is extremely sensitive to variations in gel composition and temperature. A serious limitation of this method is the relative difficulty encountered in comparing data generated in different laboratories, under apparently similar conditions.

[0529] Dideoxy fingerprinting (ddF): The dideoxy fingerprinting (ddF) is another technique developed to scan genes for the presence of mutations. The ddF technique combines components of Sanger dideoxy sequencing with SSCP. A dideoxy sequencing reaction is performed using one dideoxy terminator and then the reaction products are electrophoresed on nondenaturing polyacrylamide gels to detect alterations in mobility of the termination segments as in SSCP analysis. While ddF is an improvement over SSCP in terms of increased sensitivity, ddF requires the use of expensive dideoxynucleotides and this technique is still limited to the analysis of fragments of the size suitable for SSCP (i.e., fragments of 200-300 bases for optimal detection of mutations).

[0530] In addition to the above limitations, all of these methods are limited as to the size of the nucleic acid fragment that can be analyzed. For the direct sequencing approach, sequences of greater than 600 base pairs require cloning, with the consequent delays and expense of either deletion sub-cloning or primer walking, in order to cover the entire fragment. SSCP and DGGE have even more severe size limitations. Because of reduced sensitivity to sequence changes, these methods are not considered suitable for larger fragments. Although SSCP is reportedly able to detect 90% of single-base substitutions within a 200 base-pair fragment, the detection drops to less than 50% for 400 base pair fragments. Similarly, the sensitivity of DGGE decreases as the length of the fragment reaches 500 base-pairs. The ddF technique, as a combination of direct sequencing and SSCP, is also limited by the relatively small size of the DNA that can be screened.

[0531] According to a presently preferred embodiment of the present invention the step of searching for any of the nucleic acid sequences described here, in tumor cells or in cells derived from a cancer patient is effected by any suitable technique, including, but not limited to, nucleic acid sequencing, polymerase chain reaction, ligase chain reaction, self-sustained synthetic reaction, Q.beta.-Replicase, cycling probe reaction, branched DNA, restriction fragment length polymorphism analysis, mismatch chemical cleavage, heteroduplex analysis, allele-specific oligonucleotides, denaturing gradient gel electrophoresis, constant denaturant gel electrophoresis, temperature gradient gel electrophoresis and dideoxy fingerprinting.

[0532] Detection may also optionally be performed with a chip or other such device. The nucleic acid sample which includes the candidate region to be analyzed is preferably isolated, amplified and labeled with a reporter group. This reporter group can be a fluorescent group such as phycoerythrin. The labeled nucleic acid is then incubated with the probes immobilized on the chip using a fluidics station. describe the fabrication of fluidics devices and particularly microcapillary devices, in silicon and glass substrates.

[0533] Once the reaction is completed, the chip is inserted into a scanner and patterns of hybridization are detected. The hybridization data is collected, as a signal emitted from the reporter groups already incorporated into the nucleic acid, which is now bound to the probes attached to the chip. Since the sequence and position of each probe immobilized on the chip is known, the identity of the nucleic acid hybridized to a given probe can be determined.

[0534] It will be appreciated that when utilized along with automated equipment, the above described detection methods can be used to screen multiple samples for a disease and/or pathological condition both rapidly and easily.

Amino Acid Sequences and Peptides

[0535] The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an analog or mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. Polypeptides can be modified, e.g., by the addition of carbohydrate residues to form glycoproteins. The terms "polypeptide," "peptide" and "protein" include glycoproteins, as well as non-glycoproteins.

[0536] Polypeptide products can be biochemically synthesized such as by employing standard solid phase techniques. Such methods include but are not limited to exclusive solid phase synthesis, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry.

[0537] Solid phase polypeptide synthesis procedures are well known in the art and further described by John Morrow Stewart and Janis Dillaha Young, Solid Phase Peptide Syntheses (2nd Ed., Pierce Chemical Company, 1984).

[0538] Synthetic polypeptides can optionally be purified by preparative high performance liquid chromatography [Creighton T. (1983) Proteins, structures and molecular principles. WH Freeman and Co. N.Y.], after which their composition can be confirmed via amino acid sequencing.

[0539] In cases where large amounts of a polypeptide are desired, it can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516-544, Studier et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463.

[0540] The present invention also encompasses polypeptides encoded by the polynucleotide sequences of the present invention, as well as polypeptides according to the amino acid sequences described herein. The present invention also encompasses homologues of these polypeptides, such homologues can be at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 95% or more say 100% homologous to the amino acid sequences set forth below, as can be determined using BlastP software of the National Center of Biotechnology Information (NCBI) using default parameters, optionally and preferably including the following: filtering on (this option filters repetitive or low-complexity sequences from the query using the Seg (protein) program), scoring matrix is BLOSUM62 for proteins, word size is 3, E value is 10, gap costs are 11, 1 (initialization and extension), and number of alignments shown is 50. Finally, the present invention also encompasses fragments of the above described polypeptides and polypeptides having mutations, such as deletions, insertions or substitutions of one or more amino acids, either naturally occurring or artificially induced, either randomly or in a targeted fashion. Homology/identity of nucleic acid sequences is preferably determined by using BlastN software of the National Center of Biotechnology Information (NCBI) using default parameters, which preferably include using the DUST filter program, and also preferably include having an E value of 10, filtering low complexity sequences and a word size of 11.

[0541] It will be appreciated that peptides identified according the present invention may be degradation products, synthetic peptides or recombinant peptides as well as peptidomimetics, typically, synthetic peptides and peptoids and semipeptoids which are peptide analogs, which may have, for example, modifications rendering the peptides more stable while in a body or more capable of penetrating into cells. Such modifications include, but are not limited to N terminus modification, C terminus modification, peptide bond modification, including, but not limited to, CH2-NH, CH2-S, CH2-S.dbd.O, O.dbd.C--NH, CH2-O, CH2-CH2, S.dbd.C--NH, CH.dbd.CH or CF.dbd.CH, backbone modifications, and residue modification. Methods for preparing peptidomimetic compounds are well known in the art and are specified. Further details in this respect are provided hereinunder.

[0542] Peptide bonds (--CO--NH--) within the peptide may be substituted, for example, by N-methylated bonds (--N(CH3)-CO--), ester bonds (--C(R)H--C--O--O--C(R)--N--), ketomethylen bonds (--CO--CH2-), .alpha.-aza bonds (--NH--N(R)--CO--), wherein R is any alkyl, e.g., methyl, carba bonds (--CH2-NH--), hydroxyethylene bonds (--CH(OH)--CH2-), thioamide bonds (--CS--NH--), olefinic double bonds (--CH.dbd.CH--), retro amide bonds (--NH--CO--), peptide derivatives (--N(R)--CH2-CO--), wherein R is the "normal" side chain, naturally presented on the carbon atom.

[0543] These modifications can occur at any of the bonds along the peptide chain and even at several (2-3) at the same time.

[0544] Natural aromatic amino acids, Trp, Tyr and Phe, may be substituted for synthetic non-natural acid such as Phenylglycine, TIC, naphthylelanine (Nol), ring-methylated derivatives of Phe, halogenated derivatives of Phe or o-methyl-Tyr.

[0545] In addition to the above, the peptides of the present invention may also include one or more modified amino acids or one or more non-amino acid monomers (e.g. fatty acids, complex carbohydrates etc).

[0546] As used herein in the specification and in the claims section below the term "amino acid" or "amino acids" is understood to include the 20 naturally occurring amino acids; those amino acids often modified post-translationally in vivo, including, for example, hydroxyproline, phosphoserine and phosphothreonine; and other unusual amino acids including, but not limited to, 2-aminoadipic acid, hydroxylysine, isodesmosine, nor-valine, nor-leucine and ornithine. Furthermore, the term "amino acid" includes both D- and L-amino acids.

[0547] Table 1 non-conventional or modified amino acids which can be used with the present invention. TABLE-US-00087 TABLE 1 Non-conventional amino acid Code Non-conventional amino acid Code .alpha.-aminobutyric acid Abu L-N-methylalanine Nmala .alpha.-amino-.alpha.-methylbutyrate Mgabu L-N-methylarginine Nmarg aminocyclopropane- Cpro L-N-methylasparagine Nmasn Carboxylate L-N-methylaspartic acid Nmasp aminoisobutyric acid Aib L-N-methylcysteine Nmcys aminonorbornyl- Norb L-N-methylglutamine Nmgin Carboxylate L-N-methylglutamic acid Nmglu Cyclohexylalanine Chexa L-N-methylhistidine Nmhis Cyclopentylalanine Cpen L-N-methylisolleucine Nmile D-alanine Dal L-N-methylleucine Nmleu D-arginine Darg L-N-methyllysine Nmlys D-aspartic acid Dasp L-N-methylmethionine Nmmet D-cysteine Dcys L-N-methylnorleucine Nmnle D-glutamine Dgln L-N-methylnorvaline Nmnva D-glutamic acid Dglu L-N-methylornithine Nmorn D-histidine Dhis L-N-methylphenylalanine Nmphe D-isoleucine Dile L-N-methylproline Nmpro D-leucine Dleu L-N-methylserine Nmser D-lysine Dlys L-N-methylthreonine Nmthr D-methionine Dmet L-N-methyltryptophan Nmtrp D-ornithine Dorn L-N-methyltyrosine Nmtyr D-phenylalanine Dphe L-N-methylvaline Nmval D-proline Dpro L-N-methylethylglycine Nmetg D-serine Dser L-N-methyl-t-butylglycine Nmtbug D-threonine Dthr L-norleucine Nle D-tryptophan Dtrp L-norvaline Nva D-tyrosine Dtyr .alpha.-methyl-aminoisobutyrate Maib D-valine Dval .alpha.-methyl-.gamma.-aminobutyrate Mgabu D-.alpha.-methylalanine Dmala .alpha.-methylcyclohexylalanine Mchexa D-.alpha.-methylarginine Dmarg .alpha.-methylcyclopentylalanine Mcpen D-.alpha.-methylasparagine Dmasn .alpha.-methyl-.alpha.-napthylalanine Manap D-.alpha.-methylaspartate Dmasp .alpha.-methylpenicillamine Mpen D-.alpha.-methylcysteine Dmcys N-(4-aminobutyl)glycine Nglu D-.alpha.-methylglutamine Dmgln N-(2-aminoethyl)glycine Naeg D-.alpha.-methylhistidine Dmhis N-(3-aminopropyl)glycine Norn D-.alpha.-methylisoleucine Dmile N-amino-.alpha.-methylbutyrate Nmaabu D-.alpha.-methylleucine Dmleu .alpha.-napthylalanine Anap D-.alpha.-methyllysine Dmlys N-benzylglycine Nphe D-.alpha.-methylmethionine Dmmet N-(2-carbamylethyl)glycine Ngln D-.alpha.-methylornithine Dmorn N-(carbamylmethyl)glycine Nasn D-.alpha.-methylphenylalanine Dmphe N-(2-carboxyethyl)glycine Nglu D-.alpha.-methylproline Dmpro N-(carboxymethyl)glycine Nasp D-.alpha.-methylserine Dmser N-cyclobutylglycine Ncbut D-.alpha.-methylthreonine Dmthr N-cycloheptylglycine Nchep D-.alpha.-methyltryptophan Dmtrp N-cyclohexylglycine Nchex D-.alpha.-methyltyrosine Dmty N-cyclodecylglycine Ncdec D-.alpha.-methylvaline Dmval N-cyclododeclglycine Ncdod D-.alpha.-methylalnine Dnmala N-cyclooctylglycine Ncoct D-.alpha.-methylarginine Dnmarg N-cyclopropylglycine Ncpro D-.alpha.-methylasparagine Dnmasn N-cycloundecylglycine Ncund D-.alpha.-methylasparatate Dnmasp N-(2,2-diphenylethyl)glycine Nbhm D-.alpha.-methylcysteine Dnmcys N-(3,3- Nbhe diphenylpropyl)glycine D-N-methylleucine Dnmleu N-(3-indolylyethyl) glycine Nhtrp D-N-methyllysine Dnmlys N-methyl-.gamma.-aminobutyrate Nmgabu N- Nmchexa D-N-methylmethionine Dnmmet methylcyclohexylalanine D-N-methylornithine Dnmorn N-methylcyclopentylalanine Nmcpen N-methylglycine Nala D-N-methylphenylalanine Dnmphe N-methylaminoisobutyrate Nmaib D-N-methylproline Dnmpro N-(1-methylpropyl)glycine Nile D-N-methylserine Dnmser N-(2-methylpropyl)glycine Nile D-N-methylserine Dnmser N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr D-N-methyltryptophan Dnmtrp N-(1-methylethyl)glycine Nva D-N-methyltyrosine Dnmtyr N-methyla-napthylalanine Nmanap D-N-methylvaline Dnmval N-methylpenicillamine Nmpen .gamma.-aminobutyric acid Gabu N-(p-hydroxyphenyl)glycine Nhtyr L-t-butylglycine Tbug N-(thiomethyl)glycine Ncys L-ethylglycine Etg penicillamine Pen L-homophenylalanine Hphe L-.alpha.-methylalanine Mala L-.alpha.-methylarginine Marg L-.alpha.-methylasparagine Masn L-.alpha.-methylaspartate Masp L-.alpha.-methyl-t-butylglycine Mtbug L-.alpha.-methylcysteine Mcys L-methylethylglycine Metg L-.alpha.-methylglutamine Mgln L-.alpha.-methylglutamate Mglu L-.alpha.-methylhistidine Mhis L-.alpha.-methylhomo Mhphe phenylalanine L-.alpha.-methylisoleucine Mile N-(2-methylthioethyl)glycine Nmet D-N-methylglutamine Dnmgln N-(3- Narg guanidinopropyl)glycine D-N-methylglutamate Dnmglu N-(1-hydroxyethyl)glycine Nthr D-N-methylhistidine Dnmhis N-(hydroxyethyl)glycine Nser D-N-methylisoleucine Dnmile N-(imidazolylethyl)glycine Nhis D-N-methylleucine Dnmleu N-(3-indolylyethyl)glycine Nhtrp D-N-methyllysine Dnmlys N-methyl-.gamma.-aminobutyrate Nmgabu N- Nmchexa D-N-methylmethionine Dnmmet methylcyclohexylalanine D-N-methylornithine Dnmorn N-methylcyclopentylalanine Nmcpen N-methylglycine Nala D-N-methylphenylalanine Dnmphe N-methylaminoisobutyrate Nmaib D-N-methylproline Dnmpro N-(1-methylpropyl)glycine Nile D-N-methylserine Dnmser N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr D-N-methyltryptophan Dnmtrp N-(1-methylethyl)glycine Nval D-N-methyltyrosine Dnmtyr N-methyla-napthylalanine Nmanap D-N-methylvaline Dnmval N-methylpenicillamine Nmpen .gamma.-aminobutyric acid Gabu N-(p-hydroxyphenyl)glycine Nhtyr L-t-butylglycine Tbug N-(thiomethyl)glycine Ncys L-ethylglycine Etg penicillamine Pen L-homophenylalanine Hphe L-.alpha.-methylalanine Mala L-.alpha.-methylarginine Marg L-.alpha.-methylasparagine Masn L-.alpha.-methylaspartate Masp L-.alpha.-methyl-t-butylglycine Mtbug L-.alpha.-methylcysteine Mcys L-methylethylglycine Metg L-.alpha.-methylglutamine Mgln L-.alpha.-methylglutamate Mglu L-.alpha.-methylhistidine Mhis L-.alpha.- Mhphe methylhomophenylalanine L-.alpha.-methylisoleucine Mile N-(2-methylthioethyl)glycine Nmet L-.alpha.-methylleucine Mleu L-.alpha.-methyllysine Mlys L-.alpha.-methylmethionine Mmet L-.alpha.-methylnorleucine Mnle L-.alpha.-methylnorvaline Mnva L-.alpha.-methylornithine Morn L-.alpha.-methylphenylalanine Mphe L-.alpha.-methylproline Mpro L-.alpha.-methylserine mser L-.alpha.-methylthreonine Mthr L-.alpha.-methylvaline Mtrp L-.alpha.-methyltyrosine Mtyr L-.alpha.-methylleucine Mval L-N- Nmhphe Nnbhm methylhomophenylalanine N-(N-(2,2-diphenylethyl) N-(N-(3,3-diphenylpropyl) carbamylmethyl-glycine Nnbhm carbamylmethyl(1)glycine Nnbhe 1-carboxy-1-(2,2-diphenylethylamino) Nmbc cyclopropane

[0548] Since the peptides of the present invention are preferably utilized in diagnostics which require the peptides to be in soluble form, the peptides of the present invention preferably include one or more non-natural or natural polar amino acids, including but not limited to serine and threonine which are capable of increasing peptide solubility due to their hydroxyl-containing side chain.

[0549] The peptides of the present invention are preferably utilized in a linear form, although it will be appreciated that in cases where cyclicization does not severely interfere with peptide characteristics, cyclic forms of the peptide can also be utilized.

[0550] The peptides of present invention can be biochemically synthesized such as by using standard solid phase techniques. These methods include exclusive solid phase synthesis well known in the art, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry.

[0551] Synthetic peptides can be purified by preparative high performance liquid chromatography and the composition of which can be confirmed via amino acid sequencing.

[0552] In cases where large amounts of the peptides of the present invention are desired, the peptides of the present invention can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516-544, Studier et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463 and also as described above.

Antibodies

[0553] "Antibody" refers to a polypeptide ligand that is preferably substantially encoded by an immunoglobulin gene or immunoglobulin genes, or fragments thereof, which specifically binds and recognizes an epitope (e.g., an antigen). The recognized immunoglobulin genes include the kappa and lambda light chain constant region genes, the alpha, gamma, delta, epsilon and mu heavy chain constant region genes, and the myriad-immunoglobulin variable region genes. Antibodies exist, e.g., as intact immunoglobulins or as a number of well characterized fragments produced by digestion with various peptidases. This includes, e.g., Fab' and F(ab)'.sub.2 fragments. The term "antibody," as used herein, also includes antibody fragments either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA methodologies. It also includes polyclonal antibodies, monoclonal antibodies, chimeric antibodies, humanized antibodies, or single chain antibodies. "Fc" portion of an antibody refers to that portion of an immunoglobulin heavy chain that comprises one or more heavy chain constant region domains, CH1, CH2 and CH3, but does not include the heavy chain variable region.

[0554] The functional fragments of antibodies, such as Fab, F(ab')2, and Fv that are capable of binding to macrophages, are described as follows: (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule, can be produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy chain; (2) Fab', the fragment of an antibody molecule that can be obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fab' fragments are obtained per antibody molecule; (3) (Fab')2, the fragment of the antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; F(ab')2 is a dimer of two Fab' fragments held together by two disulfide bonds; (4) Fv, defined as a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and (5) Single chain antibody ("SCA"), a genetically engineered molecule containing the variable region of the light chain and the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule.

[0555] Methods of producing polyclonal and monoclonal antibodies as well as fragments thereof are well known in the art (See for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1988, incorporated herein by reference).

[0556] Antibody fragments according to the present invention can be prepared by proteolytic hydrolysis of the antibody or by expression in E. coli or mammalian cells (e.g. Chinese hamster ovary cell culture or other protein expression systems) of DNA encoding the fragment. Antibody fragments can be obtained by pepsin or papain digestion of whole antibodies by conventional methods. For example, antibody fragments can be produced by enzymatic cleavage of antibodies with pepsin to provide a 5S fragment denoted F(ab')2. This fragment can be further cleaved using a thiol reducing agent, and optionally a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages, to produce 3.5S Fab' monovalent fragments. Alternatively, an enzymatic cleavage using pepsin produces two monovalent Fab' fragments and an Fc fragment directly. These methods are described, for example, by Goldenberg, U.S. Pat. Nos. 4,036,945 and 4,331,647, and references contained therein, which patents are hereby incorporated by reference in their entirety. See also Porter, R. R. [Biochem. J. 73: 119-126 (1959)]. Other methods of cleaving antibodies, such as separation of heavy chains to form monovalent light-heavy chain fragments, further cleavage of fragments, or other enzymatic, chemical, or genetic techniques may also be used, so long as the fragments bind to the antigen that is recognized by the intact antibody.

[0557] Fv fragments comprise an association of VH and VL chains. This association may be noncovalent, as described in Inbar et al. [Proc. Nat'l Acad. Sci. USA 69:2659-62 (19720]. Alternatively, the variable chains can be linked by an intermolecular disulfide bond or cross-linked by chemicals such as glutaraldehyde. Preferably, the Fv fragments comprise VH and VL chains connected by a peptide linker. These single-chain antigen binding proteins (sFv) are prepared by constructing a structural gene comprising DNA sequences encoding the VH and VL domains connected by an oligonucleotide. The structural gene is inserted into an expression vector, which is subsequently introduced into a host cell such as E. coli. The recombinant host cells synthesize a single polypeptide chain with a linker peptide bridging the two V domains. Methods for producing sFvs are described, for example, by [Whitlow and Filpula, Methods 2: 97-105 (1991); Bird et al., Science 242:423-426 (1988); Pack et al., Bio/Technology 11:1271-77 (1993); and U.S. Pat. No. 4,946,778, which is hereby incorporated by reference in its entirety.

[0558] Another form of an antibody fragment is a peptide coding for a single complementarity-determining region (CDR). CDR peptides ("minimal recognition units") can be obtained by constructing genes encoding the CDR of an antibody of interest. Such genes are prepared, for example, by using the polymerase chain reaction to synthesize the variable region from RNA of antibody-producing cells. See, for example, Larrick and Fry [Methods, 2: 106-10 (1991)].

[0559] Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab') or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)].

[0560] Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain. Humanization can be essentially performed following the method of Winter and co-workers [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)], by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.

[0561] Human antibodies can also be produced using various techniques known in the art, including phage display libraries [Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)]. The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147(1):86-95 (1991)]. Similarly, human antibodies can be made by introduction of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks et al., Bio/Technology 10,: 779-783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368 812-13 (1994); Fishwild et al., Nature Biotechnology 14, 845-51 (1996); Neuberger, Nature Biotechnology 14: 826 (1996); and-Lonberg and Huszar, Intern. Rev. Immunol. 13, 65-93 (1995).

[0562] Preferably, the antibody of this aspect of the present invention specifically binds at least one epitope of the polypeptide variants of the present invention. As used herein, the term "epitope" refers to any antigenic determinant on an antigen to which the paratope of an antibody binds.

[0563] Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or carbohydrate side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics.

[0564] Optionally, a unique epitope may be created in a variant due to a change in one or more post-translational modifications, including but not limited to glycosylation and/or phosphorylation, as described below. Such a change may also cause a new epitope to be created, for example through removal of glycosylation at a particular site.

[0565] An epitope according to the present invention may also optionally comprise part or all of a unique sequence portion of a variant according to the present invention in combination with at least one other portion of the variant which is not contiguous to the unique sequence portion in the linear polypeptide itself, yet which are able to form an epitope in combination. One or more unique sequence portions may optionally combine with one or more other non-contiguous portions of the variant (including a portion which may have high homology to a portion of the known protein) to form an epitope.

Immunoassays

[0566] In another embodiment of the present invention, an immunoassay can be used to qualitatively or quantitatively detect and analyze markers in a sample. This method comprises: providing an antibody that specifically binds to a marker; contacting a sample with the antibody; and detecting the presence of a complex of the antibody bound to the marker in the sample.

[0567] To prepare an antibody that specifically binds to a marker, purified protein markers can be used. Antibodies that specifically bind to a protein marker can be prepared using any suitable methods known in the art.

[0568] After the antibody is provided, a marker can be detected and/or quantified using any of a number of well recognized immunological binding assays. Useful assays include, for example, an enzyme immune assay (EIA) such as enzyme-linked immunosorbent assay (ELISA), a radioimmune assay (RIA), a Western blot assay, or a slot blot assay see, e.g., U.S. Pat. Nos. 4,366,241; 4,376,110; 4,517,288; and 4,837,168). Generally, a sample obtained from a subject can be contacted with the antibody that specifically binds the marker.

[0569] Optionally, the antibody can be fixed to a solid support to facilitate washing and subsequent isolation of the complex, prior to contacting the antibody with a sample. Examples of solid supports include but are not limited to glass or plastic in the form of, e.g., a microtiter plate, a stick, a bead, or a microbead. Antibodies can also be attached to a solid support.

[0570] After incubating the sample with antibodies, the mixture is washed and the antibody-marker complex formed can be detected. This can be accomplished by incubating the washed mixture with a detection reagent. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture.

[0571] Throughout the assays, incubation and/or washing steps may be required after each combination of reagents. Incubation steps can vary from about 5 seconds to several hours, preferably from about 5 minutes to about 24 hours. However, the incubation time will depend upon the assay format, marker, volume of solution, concentrations and the like. Usually the assays will be carried out at ambient temperature, although they can be conducted over a range of temperatures, such as 10.degree. C. to 40.degree. C.

[0572] The immunoassay can be used to determine a test amount of a marker in a sample from a subject. First, a test amount of a marker in a sample can be detected using the immunoassay methods described above. If a marker is present in the sample, it will form an antibody-marker complex with an antibody that specifically binds the marker under suitable incubation conditions described above. The amount of an antibody-marker complex can optionally be determined by comparing to a standard. As noted above, the test amount of marker need not be measured in absolute units, as long as the unit of measurement can be compared to a control amount and/or signal.

[0573] Preferably used are antibodies which specifically interact with the polypeptides of the present invention and not with wild type proteins or other isoforms thereof, for example. Such antibodies are directed, for example, to the unique sequence portions of the polypeptide variants of the present invention, including but not limited to bridges, heads, tails and insertions described in greater detail below. Preferred embodiments of antibodies according to the present invention are described in greater detail with regard to the section entitled "Antibodies".

[0574] Radio-immunoassay (RIA): In one version, this method involves precipitation of the desired substrate and in the methods detailed hereinbelow, with a specific antibody and radiolabelled antibody binding protein (e.g., protein A labeled with I.sup.125) immobilized on a precipitable carrier such as agarose beads. The number of counts in the precipitated pellet is proportional to the amount of substrate.

[0575] In an alternate version of the RIA, a labeled substrate and an unlabelled antibody binding protein are employed. A sample containing an unknown amount of substrate is added in varying amounts. The decrease in precipitated counts from the labeled substrate is proportional to the amount of substrate in the added sample.

[0576] Enzyme linked immunosorbent assay (ELISA): This method involves fixation of a sample (e.g., fixed cells or a proteinaceous solution) containing a protein substrate to a surface such as a well of a microtiter plate. A substrate specific antibody coupled to an enzyme is applied and allowed to bind to the substrate. Presence of the antibody is then detected and quantitated by a colorimetric reaction employing the enzyme coupled to the antibody. Enzymes commonly employed in this method include horseradish peroxidase and alkaline phosphatase. If well calibrated and within the linear range of response, the amount of substrate present in the sample is proportional to the amount of color produced. A substrate standard is generally employed to improve quantitative accuracy.

[0577] Western blot: This method involves separation of a substrate from other protein by means of an acrylamide gel followed by transfer of the substrate to a membrane (e.g., nylon or PVDF). Presence of the substrate is then detected by antibodies specific to the substrate, which are in turn detected by antibody binding reagents. Antibody binding reagents may be, for example, protein A, or other antibodies. Antibody binding reagents may be radiolabelled or enzyme linked as described hereinabove. Detection may be by autoradiography, colorimetric reaction or chemiluminescence. This method allows both quantitation of an amount of substrate and determination of its identity by a relative position on the membrane which is indicative of a migration distance in the acrylamide gel during electrophoresis.

[0578] Immunohistochemical analysis: This method involves detection of a substrate in situ in fixed cells by substrate specific antibodies. The substrate specific antibodies may be enzyme linked or linked to fluorophores. Detection is by microscopy and subjective evaluation. If enzyme linked antibodies are employed, a colorimetric reaction may be required.

[0579] Fluorescence activated cell sorting (FACS): This method involves detection of a substrate in situ in cells by substrate specific antibodies. The substrate specific antibodies are linked to fluorophores. Detection is by means of a cell sorting machine which reads the wavelength of light emitted from each cell as it passes through a light beam. This method may employ two or more antibodies simultaneously.

Radio-Imaging Methods

[0580] These methods include but are not limited to, positron emission tomography (PET) single photon emission computed tomography (SPECT). Both of these techniques are non-invasive, and can be used to detect and/or measure a wide variety of tissue events and/or functions, such as detecting cancerous cells for example. Unlike PET, SPECT can optionally be used with two labels simultaneously. SPECT has some other advantages as well, for example with regard to cost and the types of labels that can be used. For example, US Patent No. 6,696,686 describes the use of SPECT for detection of breast cancer, and is hereby incorporated by reference as if fully set forth herein.

Display Libraries

[0581] According to still another aspect of the present invention there is provided a display library comprising a plurality of display vehicles (such as phages, viruses or bacteria) each displaying at least 6, at least 7, at least 8, at least 9, at least 10, 10-15, 12-17, 15-20, 15-30 or 20-50 consecutive amino acids derived from the polypeptide sequences of the present invention.

[0582] Methods of constructing such display libraries are well known in the art. Such methods are described in, for example, Young A C, et al., "The three-dimensional structures of a polysaccharide binding antibody to Cryptococcus neoformans and its complex with a peptide from a phage display library: implications for the identification of peptide mimotopes" J Mol Biol Dec. 12, 1997;274(4):622-34; Giebel L B et al. "Screening of cyclic peptide phage libraries identifies ligands that bind streptavidin with high affinities" Biochemistry Nov. 28, 1995;34(47):15430-5; Davies E L et al., "Selection of specific phage-display antibodies using libraries derived from chicken immunoglobulin genes" J Immunol Methods Oct. 12, 1995;186(l):125-35; Jones C R T al. "Current trends in molecular recognition and bioseparation" J Chromatogr A Jul. 14, 1995;707(1):3-22; Deng S J et al. "Basis for selection of improved carbohydrate-binding single-chain antibodies from synthetic gene libraries" Proc Natl Acad Sci USA May 23, 1995;92(11):4992-6; and Deng S J et al. "Selection of antibody single-chain variable fragments with improved carbohydrate binding by phage display" J Biol Chem Apr. 1, 1994;269(13):9533-8, which are incorporated herein by reference.

[0583] The following sections relate to Candidate Marker Examples (first section) and to Experimental Data for these Marker Examples (second section).

CANDIDATE MARKER EXAMPLES SECTION

[0584] This Section relates to Examples of sequences according to the present invention, including illustrative methods of selection thereof.

DESCRIPTION OF THE METHODOLOGY UNDERTAKEN TO UNCOVER THE BIOMOLECULAR SEQUENCES OF THE PRESENT INVENTION

[0585] Human ESTs and cDNAs were obtained from GenBank versions 136 (Jun. 15, 2003 ftp.ncbi.nih.gov/genbank/release.notes/gb136.release.notes); NCBI genome assembly of April 2003; RefSeq sequences from June 2003; Genbank version 139 (December 2003); Human Genome from NCBI (Build 34) (from October 2003); RefSeq sequences from December 2003; and from LifeSeq library of Incyte Corp (Wilmington, Del., USA; ESTs only). With regard to GenBank sequences, the human EST sequences from the EST (GBEST) section and the human mRNA sequences from the primate (GBPRI) section were used; also the human nucleotide RefSeq mRNA sequences were used (see for example www.ncbi.nlm.nih.gov/Genbank/GenbankOverview.html and for a reference to the EST section, see www.ncbi.nlm.nih.gov/dbEST/; a general reference to dbEST, the EST database in GenBank, may be found in Boguski et al, Nat Genet. 1993 Aug.;4(4):332-3; all of which are hereby incorporated by reference as if fully set forth herein).

[0586] Novel splice variants were predicted using the LEADS clustering and assembly system as described in Sorek, R., Ast, G. & Graur, D. Alu-containing exons are alternatively spliced. Genome Res 12, 1060-7 (2002); U.S. Pat. No: 6,625,545; and U.S. patent application Ser. No. 10/426,002, published as US20040101876 on May 27 2004; all of which are hereby incorporated by reference as if fully set forth herein. Briefly, the software cleans the expressed sequences from repeats, vectors and immunoglobulins. It then aligns the expressed sequences to the genome taking alternatively splicing into account and clusters overlapping expressed sequences into "clusters" that represent genes or partial genes.

[0587] These were annotated using the GeneCarta (Compugen, Tel-Aviv, Israel) platform. The GeneCarta platform includes a rich pool of annotations, sequence information (particularly of spliced sequences), chromosomal information, alignments, and additional information such as SNPs, gene ontology terms, expression profiles, functional analyses, detailed domain structures, known and predicted proteins and detailed homology reports.

[0588] A brief explanation is provided with regard to the method of selecting the candidates. However, it should noted that this explanation is provided for descriptive purposes only, and is not intended to be limiting in any way. The potential markers were identified by a computational process that was designed to find genes and/or their splice variants that are over-expressed in tumor tissues, by using databases of expressed sequences. Various parameters related to the information in the EST libraries, determined according to a manual classification process, were used to assist in locating genes and/or splice variants thereof that are over-expressed in cancerous tissues. The detailed description of the selection method is presented in Example 1 below. The cancer biomarkers selection engine and the following wet validation stages are schematically summarized in FIG. 1.

EXAMPLE 1

Identification of Differentially Expressed Gene Products--Algorithm

[0589] In order to distinguish between differentially expressed gene products and constitutively expressed genes (i.e., house keeping genes ) an algorithm based on an analysis of frequencies was configured. A specific algorithm for identification of transcripts over expressed in cancer is described hereinbelow.

[0590] Dry Analysis

[0591] Library annotation--EST libraries are manually classified according to: [0592] (i) Tissue origin [0593] (ii) Biological source--Examples of frequently used biological sources for construction of EST libraries include cancer cell-lines; normal tissues; cancer tissues; fetal tissues; and others such as normal cell lines and pools of normal cell-lines, cancer cell-lines and combinations thereof. A specific description of abbreviations used below with regard to these tissues/cell lines etc is given above. [0594] (iii) Protocol of library construction--various methods are known in the art for library construction including normalized library construction; non-normalized library construction; subtracted libraries; ORESTES and others. It will be appreciated that at times the protocol of library construction is not indicated.

[0595] The following rules were followed:

[0596] EST libraries originating from identical biological samples are considered as a single library.

[0597] EST libraries which included above-average levels of contamination, such as DNA contamination for example, were eliminated. The presence of such contamination was determined as follows. For each library, the number of unspliced ESTs that are not fully contained within other spliced sequences was counted. If the percentage of such sequences (as compared to all other sequences) was at least 4 standard deviations above the average for all libraries being analyzed, this library was tagged as being contaminated and was eliminated from further consideration in the below analysis (see also Sorek, R. & Safer, H. M. A novel algorithm for computational identification of contaminated EST libraries. Nucleic Acids Res 31, 1067-74 (2003)for further details).

[0598] Clusters (genes) having at least five sequences including at least two sequences from the tissue of interest were analyzed. Splice variants were identified by using the LEADS software package as described above.

EXAMPLE 2

Identification of Genes Over Expressed in Cancer

[0599] Two different scoring algorithms were developed.

[0600] Libraries score--candidate sequences which are supported by a number of cancer libraries, are more likely to serve as specific and effective diagnostic markers.

[0601] The basic algorithm--for each cluster the number of cancer and normal libraries contributing sequences to the cluster was counted. Fisher exact test was used to check if cancer libraries are significantly over-represented in the cluster as compared to the total number of cancer and normal libraries.

[0602] Library counting: Small libraries (e.g., less than 1000 sequences) were excluded from consideration unless they participate in the cluster. For this reason, the total number of libraries is actually adjusted for each cluster.

[0603] Clones no. score--Generally, when the number of ESTs is much higher in the cancer libraries relative to the normal libraries it might indicate actual over-expression.

[0604] The algorithm--

[0605] Clone counting: For counting EST clones each library protocol class was given a weight based on our belief of how much the protocol reflects actual expression levels:

[0606] (i) non-normalized: 1

[0607] (ii) normalized: 0.2

[0608] (iii) all other classes: 0.1

[0609] Clones number score--The total weighted number of EST clones from cancer libraries was compared to the EST clones from normal libraries. To avoid cases where one library contributes to the majority of the score, the contribution of the library that gives most clones for a given cluster was limited to 2 clones.

[0610] The score was computed as c + 1 C / n + 1 N where:

[0611] c--weighted number of "cancer" clones in the cluster.

[0612] C--weighted number of clones in all "cancer" libraries.

[0613] n--weighted number of "normal" clones in the cluster.

[0614] N--weighted number of clones in all "normal" libraries.

[0615] Clones number score significance--Fisher exact test was used to check if EST clones from cancer libraries are significantly over-represented in the cluster as compared to the total number of EST clones from cancer and normal libraries.

[0616] Two search approaches were used to find either general cancer-specific candidates or tumor specific candidates. [0617] Libraries/sequences originating from tumor tissues are counted as well as libraries originating from cancer cell-lines ("normal" cell-lines were ignored). [0618] Only libraries/sequences originating from tumor tissues are counted

EXAMPLE 3

Identification of tissue Specific Genes

[0619] For detection of tissue specific clusters, tissue libraries/sequences were compared to the total number of libraries/sequences in cluster. Similar statistical tools to those described in above were employed to identify tissue specific genes. Tissue abbreviations are the same as for cancerous tissues, but are indicated with the header "normal tissue".

[0620] The algorithm--for each tested tissue T and for each tested cluster the following were examined:

[0621] 1. Each cluster includes at least 2 libraries from the tissue T. At least 3 clones (weighed--as described above) from tissue T in the cluster; and

[0622] 2. Clones from the tissue T are at least 40% from all the clones participating in the tested cluster

[0623] Fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant.

EXAMPLE 4

Identification of Splice Variants Expressed in Cancer of Clusters Which are Not Over Expressed in Cancer

[0624] Cancer-Specific Splice Variants Containing a Unique Region were Identified.

[0625] Identification of unique sequence regions in splice variants A Region is defined as a group of adjacent exons that always appear or do not appear together in each splice variant.

[0626] A "segment" (sometimes referred also as "seg" or "node") is defined as the shortest contiguous transcribed region without known splicing inside.

[0627] Only reliable ESTs were considered for region and segment analysis. An EST was defined as unreliable if:

[0628] (i) Unspliced;

[0629] (ii) Not covered by RNA;

[0630] (iii) Not covered by spliced ESTs; and

[0631] (iv) Alignment to the genome ends in proximity of long poly-A stretch or starts in proximity of long poly-T stretch.

[0632] Only reliable regions were selected for further scoring. Unique sequence regions were considered reliable if:

[0633] (i) Aligned to the genome; and

[0634] (ii) Regions supported by more than 2 ESTs.

[0635] The algorithm

[0636] Each unique sequence region divides the set of transcripts into 2 groups:

[0637] (i) Transcripts containing this region (group TA).

[0638] (ii) Transcripts not containing this region (group TB).

[0639] The set of EST clones of every cluster is divided into 3 groups:

[0640] (i) Supporting (originating from) transcripts of group TA (S1).

[0641] (ii) Supporting transcripts of group TB (S2).

[0642] (iii) Supporting transcripts from both groups (S3).

[0643] Library and clones number scores described above were given to S1 group.

[0644] Fisher Exact Test P-values were used to check if:

[0645] S1 is significantly enriched by cancer EST clones compared to S2; and

[0646] S1 is significantly enriched by cancer EST clones compared to cluster background (S1+S2+S3).

[0647] Identification of unique sequence regions and division of the group of transcripts accordingly is illustrated in FIG. 2. Each of these unique sequence regions corresponds to a segment, also termed herein a "node".

[0648] Region 1: common to all transcripts, thus it is preferably not considered for determining differential expression between variants; Region 2: specific to Transcript 1; Region 3: specific to Transcripts 2+3; Region 4: specific to Transcript 3; Region 5: specific to Transcripts 1 and 2; Region 6: specific to Transcript 1.

EXAMPLE 5

Identification of Cancer Specific Splice Variants of Genes Over Expressed in Cancer

[0649] A search for EST supported (no mRNA) regions for genes of:

[0650] (i) known cancer markers

[0651] (ii) Genes shown to be over-expressed in cancer in published micro-array experiments.

[0652] Reliable EST supported-regions were defined as supported by minimum of one of the following:

[0653] (i) 3 spliced ESTs; or

[0654] (ii) 2 spliced ESTs from 2 libraries;

[0655] (iii) 10 unspliced ESTs from 2 libraries, or

[0656] (iv) 3 libraries.

ACTUAL MARKER EXAMPLES

[0657] The following examples relate to specific actual marker examples.

EXPERIMENTAL EXAMPLES SECTION

[0658] This Section relates to Examples describing experiments involving these sequences, and illustrative, non-limiting examples of methods, assays and uses thereof. The materials and experimental procedures are explained first, as all experiments used them as a basis for the work that was performed.

[0659] The markers of the present invention were tested with regard to their expression in various cancerous and non-cancerous tissue samples. A description of the samples used in the panel is provided in Table 1 below. A description of the samples used in the normal tissue panel is provided in Table 2 below. Tests were then performed as described in the "Materials and Experimental Procedures" section below. TABLE-US-00088 TABLE 1 Tissue samples in testing panel sample sex/ rename Lot no source pathology grade age TNM stage 52-B-ILC G1 A605360 Biochain Invasive 1 F/60 Lobular Carcinoma 51-B-IDC G1 A605361 Biochain IDC 1 F/79 6-A-IDC G1 7238T ABS IDC 1 F/60 T2N0M0 stage 2A 7-A-IDC G2 7263T ABS IDC 2 F/43 T1N0M0 stage 1 12-A-IDC G2 1432T ABS IDC 2 F/46 T2N0M0 stage 2A 13-A-IDC G2 A0133T ABS IDC 2 F/63 T2N1a Mx 14-A-IDC G2 A0135T ABS IDC 2 F/37 T2N2Mx 15-A-IDC G2 7259T ABS IDC 2 F/59 T3N1M0 stage 3A 16-A-IDC G2 4904020032T ABS IDC 2 NA T3N1Mx 17-A-IDC G2 4904020036T ABS IDC 2-3 NA T3N1Mx 43-B-IDC G2 A609183 Biochain IDC 2 F/40 44-B-IDC G2 A609198 Biochain IDC 2 F/77 45-B-IDC G2 A609181 Biochain IDC 2 F/58 48-B-IDC G2 A609222 Biochain IDC 2 F/44 49-B-IDC G2 A609223 Biochain IDC 2 F/54 50-B-IDC G2 A609224 Biochain IDC 2 F/69 53-B-IDC G2 A605151 Biochain IDC 2 F/44 54-B-IDC G2 A605353 Biochain IDC 2 F/41 55-B-IDC G2 A609179 Biochain IDC 2 F/42 61-B-IDC G2 A610029 Biochain IDC 2 F/46 62-B-IDC G2 A609194 Biochain IDC 2 F/51 47-B-IDC G2 A609221 Biochain IDC 2 46-B-Carci G2 A609177 Biochain Carcinoma 2 F/48 26-A-IDC G3 7249T ABS IDC 3 F/60 T2N0M0 stage 2A 27-A-IDC G3 4907020072T ABS IDC 3 NA T2N0Mx 42-A-IDC G3 6005020031T ABS IDC 3 NA T1cN0 Mx 31-CG-IDC CG-154 Ichilov IDC NA 32-A-Muc 7116T ABS Mucinous F/54 T2N0M0 stage Carci carcinoma 2A 35-A-N M6 7238N ABS Normal F/60 matched to 6T 36-A-N M7 7263N ABS Normal F/43 matched to 7T 39-A-N M15 7259N ABS Normal F/59 matched to 15T 40-A-N M12 1432N ABS Normal F/46 matched to 12T 41-A-N M26 7249N ABS Normal F/60 matched to 26T 56-B-N A609235 Biochain Normal F/59 PM 57-B-N A609233 Biochain Normal F/34 PM 58-B-N A609232 Biochain Normal F/65 PM 59-B-N A607155 Biochain Normal F/35 PM 60-B-N A609234 Biochain Normal F/36 PM 63-Am-N 26486 Ambion Normal PS F/43 64-Am-N 23036 Ambion Normal F/57 PM 65-Am-N 31410 Ambion Normal F/63 PM 66-Am-N 36678 Ambion Normal F/45 PM 67-Am-N 073P010602086A Ambion Normal F/64 PM

[0660] TABLE-US-00089 TABLE 2 Tissue samples in normal panel: Lot no. Source Tissue Pathology Sex/Age 1-Am-Colon (C71) 071P10B Ambion Colon PM F/43 2-B-Colon (C69) A411078 Biochain Colon PM-Pool of 10 M&F 3-Cl-Colon (C70) 1110101 Clontech Colon PM-Pool of 3 M&F 4-Am-Small Intestine 091P0201A Ambion Small Intestine PM M/75 5-B-Small Intestine A501158 Biochain Small Intestine PM M/63 6-B-Rectum A605138 Biochain Rectum PM M/25 7-B-Rectum A610297 Biochain Rectum PM M/24 8-B-Rectum A610298 Biochain Rectum PM M/27 9-Am-Stomach 110P04A Ambion Stomach PM M/16 10-B-Stomach A501159 Biochain Stomach PM M/24 11-B-Esophagus A603814 Biochain Esophagus PM M/26 12-B-Esophagus A603813 Biochain Esophagus PM M/41 13-Am-Pancreas 071P25C Ambion Pancreas PM M/25 14-CG-Pancreas CG-255-2 Ichilov Pancreas PM M/75 15-B-Lung A409363 Biochain Lung PM F/26 16-Am-Lung (L93) 111P0103A Ambion Lung PM F/61 17-B-Lung (L92) A503204 Biochain Lung PM M/28 18-Am-Ovary (O47) 061P43A Ambion Ovary PM F/16 19-B-Ovary (O48) A504087 Biochain Ovary PM F/51 20-B-Ovary (O46) A504086 Biochain Ovary PM F/41 21-Am-Cervix 101P0101A Ambion Cervix PM F/40 22-B-Cervix A408211 Biochain Cervix PM F/36 23-B-Cervix A504089 Biochain Cervix PM-Pool of 5 M&F 24-B-Uterus A411074 Biochain Uterus PM-Pool of 10 M&F 25-B-Uterus A409248 Biochain Uterus PM F/43 26-B-Uterus A504090 Biochain Uterus PM-Pool of 5 M&F 27-B-Bladder A501157 Biochain Bladder PM M/29 28-Am-Bladder 071P02C Ambion Bladder PM M/20 29-B-Bladder A504088 Biochain Bladder PM-Pool of 5 M&F 30-Am-Placenta 021P33A Ambion Placenta PB F/33 31-B-Placenta A410165 Biochain Placenta PB F/26 32-B-Placenta A411073 Biochain Placenta PB-Pool of 5 M&F 33-B-Breast (B59) A607155 Biochain Breast PM F/36 34-Am-Breast (B63) 26486 Ambion Breast PM F/43 35-Am-Breast (B64) 23036 Ambion Breast PM F/57 36-Cl-Prostate (P53) 1070317 Clontech Prostate PB-Pool of 47 M&F 37-Am-Prostate (P42) 061P04A Ambion Prostate PM M/47 38-Am-Prostate (P59) 25955 Ambion Prostate PM M/62 39-Am-Testis 111P0104A Ambion Testis PM M/25 40-B-Testis A411147 Biochain Testis PM M/74 41-Cl-Testis 1110320 Clontech Testis PB-Pool of 45 M&F 42-CG-Adrenal CG-184-10 Ichilov Adrenal PM F/81 43-B-Adrenal A610374 Biochain Adrenal PM F/83 44-B-Heart A411077 Biochain Heart PB-Pool of 5 M&F 45-CG-Heart CG-255-9 Ichilov Heart PM M/75 46-CG-Heart CG-227-1 Ichilov Heart PM F/36 47-Am-Liver 081P0101A Ambion Liver PM M/64 48-CG-Liver CG-93-3 Ichilov Liver PM F/19 49-CG-Liver CG-124-4 Ichilov Liver PM F/34 50-Cl-BM 1110932 Clontech Bone Marrow PM-Pool of 8 M&F 51-CGEN-Blood WBC#5 CGEN Blood M 52-CGEN-Blood WBC#4 CGEN Blood M 53-CGEN-Blood WBC#3 CGEN Blood M 54-CG-Spleen CG-267 Ichilov Spleen PM F/25 55-CG-Spleen 111P0106B Ambion Spleen PM M/25 56-CG-Spleen A409246 Biochain Spleen PM F/12 56-CG-Thymus CG-98-7 Ichilov Thymus PM F/28 58-Am-Thymus 101P0101A Ambion Thymus PM M/14 59-B-Thymus A409278 Biochain Thymus PM M/28 60-B-Thyroid A610287 Biochain Thyroid PM M/27 61-B-Thyroid A610286 Biochain Thyroid PM M/24 62-CG-Thyroid CG-119-2 Ichilov Thyroid PM F/66 63-Cl-Salivary Gland 1070319 Clontech Salivary Gland PM-Pool of 24 M&F 64-Am-Kidney 111P0101B Ambion Kidney PM-Pool of 14 M&F 65-Cl-Kidney 1110970 Clontech Kidney PM-Pool of 14 M&F 66-B-Kidney A411080 Biochain Kidney PM-Pool of 5 M&F 67-CG-Cerebellum CG-183-5 Ichilov Cerebellum PM M/74 68-CG-Cerebellum CG-212-5 Ichilov Cerebellum PM M/54 69-B-Brain A411322 Biochain Brain PM M/28 70-Cl-Brain 1120022 Clontech Brain PM-Pool of 2 M&F 71-B-Brain A411079 Biochain Brain PM-Pool of 2 M&F 72-CG-Brain CG-151-1 Ichilov Brain PM F/86 73-Am-Skeletal Muscle 101P013A Ambion Skeletal Muscle PM F/28 74-Cl-Skeletal Muscle 1061038 Clontech Skeletal Muscle PM-Pool of 2 M&F

Materials and Experimental Procedures

[0661] RNA preparation--RNA was obtained from Clontech (Franklin Lakes, N.J. USA 07417, www.clontech.com), BioChain Inst. Inc. (Hayward, Calif. 94545 USA www.biochain.com), ABS (Wilmington, Del. 19801, USA, http://www.absbioreagents.com) or Ambion (Austin, Tex. 78744 USA, http://www.ambion.com). Alternatively, RNA was generated from tissue samples using TRI-Reagent (Molecular Research Center), according to Manufacturer's instructions. Tissue and RNA samples were obtained from patients or from postmortem. Total RNA samples were treated with DNaseI (Ambion) and purified using RNeasy columns (Qiagen).

[0662] RT PCR--Purified RNA (1 .mu.g) was mixed with 150 ng Random Hexamer primers (Invitrogen) and 500 .mu.M dNTP in a total volume of 15.6 .mu.l. The mixture was incubated for 5 min at 65.degree. C. and then quickly chilled on ice. Thereafter, 5 .mu.l of 5.times. SuperscriptII first strand buffer (Invitrogen), 2.4 .mu.l 0.1M DTT and 40 units RNasin (Promega) were added, and the mixture was incubated for 10 min at 25.degree. C., followed by further incubation at 42.degree. C. for 2 min. Then, 1 .mu.l (200units) of SuperscriptII (Invitrogen) was added and the reaction (final volume of 25.mu.l) was incubated for 50 min at 42.degree. C. and then inactivated at 70.degree. C. for 15 min. The resulting cDNA was diluted 1:20 in TE buffer (10 mM Tris pH=8, 1 mM EDTA pH=8).

[0663] Real-Time RT-PCR analysis--cDNA (5 .mu.l), prepared as described above, was used as a template in Real-Time PCR reactions using the SYBR Green I assay (PE Applied Biosystem) with specific primers and UNG Enzyme (Eurogentech or ABI or Roche). The amplification was effected as follows: 50.degree. C. for 2 min, 95.degree. C. for 10 min, and then 40 cycles of 95.degree. C. for 15 sec, followed by 60.degree. C. for 1 min. Detection was performed by using the PE Applied Biosystem SDS 7000. The cycle in which the reactions achieved a threshold level (Ct) of fluorescence was registered and was used to calculate the relative transcript quantity in the RT reactions. The relative quantity was calculated using the equation Q=efficiencyl .sup.-Ct. The efficiency of the PCR reaction was calculated from a standard curve, created by using serial dilutions of several reverse transcription (RT) reactions. To minimize inherent differences in the RT reaction, the resulting relative quantities were normalized to the geometric mean of the relative quantities of several housekeeping (HSKP) genes. Schematic summary of quantitative real-time PCR analysis is presented in FIG. 3. As shown, the x-axis shows the cycle number. The C.sub.T=Threshold Cycle point, which is the cycle that the amplification curve crosses the fluorescence threshold that was set in the experiment. This point is a calculated cycle number in which PCR product signal is above the background level (passive dye ROX) and still in the Geometric/Exponential phase (as shown, once the level of fluorescence crosses the measurement threshold, it has a geometrically increasing phase, during which measurements are most accurate, followed by a linear phase and a plateau phase; for quantitative measurements, the latter two phases do not provide accurate measurements). The y-axis shows the normalized reporter fluorescence. It should be noted that this type of analysis provides relative quantification.

[0664] The sequences of the housekeeping genes measured in all the examples on breast cancer panel were as follows: TABLE-US-00090 G6PD (GenBank Accession No. NM_000402 (SEQ ID NO: 918)) G6PD Forward primer: (SEQ ID NO: 919) gaggccgtcaccaagaacat G6PD Reverse primer: (SEQ ID NO: 920) ggacagccggtcagagctc G6PD-amplicon: (SEQ ID NO: 921) gaggccgtcaccaagaacattcacgagtcctgcatgagccagataggctggaaccgcatcatcgtggagaagcc- cttcgggagggacct gcagagctctgaccggctgtcc SDHA (GenBank Accession No. NM_004168 (SEQ ID NO: 922)) SDHA Forward primer: (SEQ ID NO: 923) TGGGAACAAGAGGGCATCTG SDHA reverse primer: (SEQ ID NO: 924) CCACCACTGCATCAAATTCATG SDHA-amplicon: (SEQ ID NO: 925) TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT AGTGGATCATGAATTTGATGCAGTGGTGG PBGD (GenBank Accession No. BC019323, (SEQ ID NO: 926)) PBGD Forward primer: (SEQ ID NO: 927) TGAGAGTGATTCGCGTGGG PBGD Reverse primer: (SEQ ID NO: 928) CCAGGGTACGAGGCTTTCAAT PBGD-amplicon: (SEQ ID NO: 929) TGAGAGTGATTCGCGTGGGTACCCGCAAGAGCCAGCTTGCTCGCATACAGACGGAC AGTGTGGTGGCAACATTGAAAGCCTCGTACCCTGG HPRT1 (GenBank Accession No. NM_000194, (SEQ ID NO: 930)) HPRT1 Forward primer: (SEQ ID NO: 931) TGACACTGGCAAAACAATGCA HPRT1 reverse primer: (SEQ ID NO: 932) GGTCCTTTTCACCAGCAAGCT HPRT1-amplicon: (SEQ ID NO: 933) TGACACTGGCAAAACAATGCAGACTTTGCTTTCCTTGGTCAGGCAGTATAATCCAA AGATGGTCAAGGTCGCAAGCTTGCTGGTGAAAAGGACC

[0665] The sequences of the housekeeping genes measured in all the examples on normal tissue samples panel were as follows: TABLE-US-00091 RPL19 (GenBank Accession No. NM_000981, (SEQ ID NO: 934)) RPL19 Forward primer: (SEQ ID NO: 935) TGGCAAGAAGAAGGTCTGGTTAG RPL19 reverse primer: (SEQ ID NO: 936) TGATCAGCCCATCTTTGATGAG RPL19-amplicon: (SEQ ID NO: 937) TGGCAAGAAGAAGGTCTGGTTAGACCCCAATGAGACCAATGAAATCGCCAATGCCA ACTCCCGTCAGCAGATCCGGAAGCTCATCAAAGATGGGCTGATCA TATA box (GenBank Accession No. NM_003194, (SEQ ID NO: 938)) TATA box Forward primer: (SEQ ID NO: 939) CGGTTTGCTGCGGTAATCAT TATA box Reverse primer: (SEQ ID NO: 940) TTTCTTGCTGCCAGTCTGGAC TATA box-amplicon: (SEQ ID NO: 941) CGGTTTGCTGCGGTAATCATGAGGATAAGAGAGCCACGAACCACGGCACTGATTTT CAGTTCTGGGAAAATGGTGTGCACAGGAGCCAAGAGTGAAGAACAGTCCAGACTG GCAGCAAGAAA UBC (GenBank Accession No. BC000449 (SEQ ID NO: 942)) UBC Forward primer: (SEQ ID NO: 943) ATTTGGGTCGCGGTTCTTG UBC reverse primer: (SEQ ID NO: 944) TGCCTTGACATTCTCGATGGT UBC-amplicon: (SEQ ID NO: 945) ATTTGGGTCGCGGTTCTTGTTTGTGGATCGCTGTGATCGTCACTTGACAATGCAGAT CTTCGTGAAGACTCTGACTGGTAAGACCATCACCCTCGAGG TTGAGCCCAGTGACACCATCGAGAATGTCAAGGCA SDHA (GenBank Accession No. NM_004168 (SEQ ID NO: 922)) SDHA Forward primer: (SEQ ID NO: 923) TGGGAACAAGAGGGCATCTG SDHA reverse primer: (SEQ ID NO: 924) CCACCACTGCATCAAATTCATG SDHA-amplicon: (SEQ ID NO: 925) TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT AGTGGATCATGAATTTGATGCAGTGGTGG

[0666] Oligonucleotide-Based Micro-Array Experiment Protocol--

Microarray Fabrication

[0667] Microarrays (chips) were printed by pin deposition using the MicroGrid II MGII 600 robot from BioRobotics Limited (Cambridge, UK). 50-mer oligonucleotides target sequences were designed by Compugen Ltd (Tel-Aviv, IL) as described by A. Shoshan et al, "Optical technologies and informatics", Proceedings of SPIE. Vol 4266, pp. 86-95 (2001). The designed oligonucleotides were synthesized and purified by desalting with the Sigma-Genosys system (The Woodlands, Tex., US) and all of the oligonucleotides were joined to a C6 amino-modified linker at the 5' end, or being attached directly to CodeLink slides (Cat #25-6700-01. Amersham Bioscience, Piscataway, N.J., US). The 50-mer oligonucleotides, forming the target sequences, were first suspended in Ultra-pure DDW (Cat # 01-866-1A Kibbutz Beit-Haemek, Israel) to a concentration of 50 .mu.M. Before printing the slides, the oligonucleotides were resuspended in 300 mM sodium phosphate (pH 8.5) to final concentration of 150 mM and printed at 35-40% relative humidity at 21.degree. C.

[0668] Each slide contained a total of 9792 features in 32 subarrays. Of these features, 4224 features were sequences of interest according to the present invention and negative controls that were printed in duplicate. An additional 288 features (96 target sequences printed in triplicate) contained housekeeping genes from Human Evaluation Library2, Compugen Ltd, Israel. Another 384 features are E.coli spikes 1-6, which are oligos to E-Coli genes which are commercially available in the Array Control product (Array control-sense oligo spots, Ambion Inc. Austin, Tex. Cat # 1781, Lot # 112K06).

Post-Coupling Processing of Printed Slides

[0669] After the spotting of the oligonucleotides to the glass (CodeLink) slides, the slides were incubated for 24 hours in a sealed saturated NaCl humidification chamber (relative humidity 70-75%).

[0670] Slides were treated for blocking of the residual reactive groups by incubating them in blocking solution at 50.degree. C for 15 minutes (10 ml/slide of buffer containing 0.1M Tris, 50 mM ethanolamine, 0.1% SDS). The slides were then rinsed twice with Ultra-pure DDW (double distilled water). The slides were then washed with wash solution (10 ml/slide. 4.times.SSC, 0.1% SDS)) at 50.degree. C. for 30 minutes on the shaker. The slides were then rinsed twice with Ultra-pure DDW, followed by drying by centrifugation for 3 minutes at 800 rpm.

[0671] Next, in order to assist in automatic operation of the hybridization protocol, the slides were treated with Ventana Discovery hybridization station barcode adhesives. The printed slides were loaded on a Bio-Optica (Milan, Italy) hematology staining device and were incubated for 10 minutes in 50 ml of 3-Aminopropyl Triethoxysilane (Sigma A3648 lot #122K589). Excess fluid was dried and slides were then incubated for three hours in 20 mm/Hg in a dark vacuum desiccator (Pelco 2251, Ted Pella, Inc. Redding Calif.).

[0672] The following protocol was then followed with the Genisphere 900-RP (random primer), with mini elute columns on the Ventana Discovery HybStation.TM., to perform the microarray experiments. Briefly, the protocol was performed as described with regard to the instructions and information provided with the device itself. The protocol included cDNA synthesis and labeling. cDNA concentration was measured with the TBS-380 (Turner Biosystems. Sunnyvale, Calif.) PicoFlour, which is used with the OliGreen ssDNA Quantitation reagent and kit. Hybridization was performed with the Ventana Hybridization device, according to the provided protocols (Discovery Hybridization Station Tuscon Ariz.).

[0673] The slides were then scanned with GenePix 4000B dual laser scanner from Axon Instruments Inc, and analyzed by GenePix Pro 5.0 software.

[0674] Schematic summary of the oligonucleotide based microarray fabrication and the experimental flow is presented in FIGS. 4 and 5.

[0675] Briefly, as shown in FIG. 4, DNA oligonucleotides at 25 uM were deposited (printed) onto Amersham `CodeLink` glass slides generating a well defined `spot`. These slides are covered with a long-chain, hydrophilic polymer chemistry that creates an active 3-D surface that covalently binds the DNA oligonucleotides 5'-end via the C6-amine modification. This binding ensures that the full length of the DNA oligonucleotides is available for hybridization to the cDNA and also allows lower background, high sensitivity and reproducibility.

[0676] FIG. 5 shows a schematic method for performing the microarray experiments. It should be noted that stages on the left-hand or right-hand side may optionally be performed in any order, including in parallel, until stage 4 (hybridization). Briefly, on the left-hand side, the target oligonucleotides are being spotted on a glass microscope slide (although optionally other materials could be used) to form a spotted slide (stage 1). On the right hand side, control sample RNA and cancer sample RNA are Cy3 and Cy5 labeled, respectively (stage 2), to form labeled probes. It should be noted that the control and cancer samples come from corresponding tissues (for example, normal prostate tissue and cancerous prostate tissue). Furthermore, the tissue from which the RNA was taken is indicated below in the specific examples of data for particular clusters, with regard to overexpression of an oligonucleotide from a "chip" (microarray), as for example "prostate" for chips in which prostate cancerous tissue and normal tissue were tested as described above. In stage 3, the probes are mixed. In stage 4, hybridization is performed to form a processed slide. In stage 5, the slide is washed and scanned to form an image file, followed by data analysis in stage 6.

Description for Cluster T10888

[0677] Cluster T10888 features 4 transcript(s) and 8 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. TABLE-US-00092 TABLE 1 Transcripts of interest Transcript Name Sequence ID No. T10888_PEA_1_T1 1 T10888_PEA_1_T4 2 T10888_PEA_1_T5 3 T10888_PEA_1_T6 4

[0678] TABLE-US-00093 TABLE 2 Segments of interest Segment Name Sequence ID No. T10888_PEA_1_node_11 5 T10888_PEA_1_node_12 6 T10888_PEA_1_node_17 7 T10888_PEA_1_node_4 8 T10888_PEA_1_node_6 9 T10888_PEA_1_node_7 10 T10888_PEA_1_node_9 11 T10888_PEA_1_node_15 12

[0679] TABLE-US-00094 TABLE 3 Proteins of interest Protein Name Sequence ID No. T10888_PEA_1_P2 14 T10888_PEA_1_P4 15 T10888_PEA_1_P5 16 T10888_PEA_1_P6 17

[0680] These sequences are variants of the known protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13) (SwissProt accession identifier CEA6_HUMAN; known also according to the synonyms Normal cross-reacting antigen; Nonspecific crossreacting antigen; CD66c antigen), SEQ ID NO:13, referred to herein as the previously known protein.

[0681] The sequence for protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13) is given at the end of the application, as "Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13) amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. TABLE-US-00095 TABLE 4 Amino acid mutations for Known Protein SNP position(s) on amino acid sequence Comment 138 F -> L 239 V -> G

[0682] Protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13) localization is believed to be Attached to the membrane by a GPI-anchor.

[0683] The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Cancer. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Immunostimulant. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Imaging agent; Anticancer; Immunostimulant; Immunoconjugate; Monoclonal antibody, murine; Antisense therapy; antibody.

[0684] The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: signal transduction; cell-cell signaling, which are annotation(s) related to Biological Process; and integral plasma membrane protein, which are annotation(s) related to Cellular Component.

[0685] The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

[0686] Cluster T10888 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the right hand column of the table and the numbers on the y-axis of FIG. 6 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

[0687] Overall, the following results were obtained as shown with regard to the histograms in FIG. 6 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma. TABLE-US-00096 TABLE 5 Normal tissue distribution Name of Tissue Number Bladder 0 Colon 107 Epithelial 52 General 22 head and neck 40 Lung 237 Breast 0 pancreas 32 Prostate 12 Stomach 0

[0688] TABLE-US-00097 TABLE 6 P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 Bladder 5.4e-01 3.4e-01 5.6e-01 1.8 4.6e-01 1.9 Colon 1.2e-01 1.7e-01 2.8e-05 3.7 7.9e-04 2.8 epithelial 3.3e-02 2.1e-01 2.8e-20 2.8 4.8e-10 1.9 General 3.3e-05 2.2e-03 1.9e-44 4.9 4.6e-27 3.3 head and neck 4.6e-01 4.3e-01 1 0.8 7.5e-01 1.0 Lung 7.6e-01 8.2e-01 8.9e-01 0.6 1 0.3 Breast 3.7e-02 4.1e-02 1.5e-01 3.3 3.1e-01 2.4 pancreas 2.6e-01 2.4e-01 8.6e-23 2.8 1.5e-19 4.5 Prostate 9.1e-01 9.3e-01 4.1e-02 1.2 1.0e-01 1.0 Stomach 4.5e-02 5.6e-02 5.1e-04 4.1 4.7e-04 6.3

[0689] As noted above, cluster T10888 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13). A description of each variant protein according to the present invention is now provided.

[0690] Variant protein T10888_PEA.sub.--1_P2 (SEQ ID NO:14) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA.sub.--1_T1 (SEQ ID NO:1). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0691] Comparison report between T10888_PEA.sub.--1_P2 (SEQ ID NO:14) and CEA6_HUMAN (SEQ ID NO:13):

[0692] 1. An isolated chimeric polypeptide encoding for T10888_PEA.sub.--1_P2 (SEQ ID NO:14), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVS corresponding to amino acids 1-319 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-319 of T10888_PEA.sub.--1_P2 (SEQ ID NO:14), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DWTRP (SEQ ID NO:999) corresponding to amino acids 320-324 of T10888_PEA.sub.--1_P2 (SEQ ID NO:14), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0693] 2. An isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P2 (SEQ ID NO:14), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DWTRP (SEQ ID NO:999) in T10888_PEA.sub.--1_P2 (SEQ ID NO:14).

[0694] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0695] Variant protein T10888_PEA.sub.--1_P2 (SEQ ID NO:14) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA.sub.--1_P2 (SEQ ID NO:14) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00098 TABLE 7 Amino acid mutations SNP position(s) on amino acid Alternative sequence amino acid(s) Previously known SNP? 13 V -> No 232 N -> D No 324 P -> No 63 I -> No 92 G -> No

[0696] Variant protein T10888_PEA.sub.--1_P2 (SEQ ID NO:14) is encoded by the following transcript(s): T10888_PEA.sub.--1_T1 (SEQ ID NO:1), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA.sub.--1_T1 (SEQ ID NO:1) is shown in bold; this coding portion starts at position 151 and ends at position 1122. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA.sub.--1.sub.--P2 (SEQ ID NO:14) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00099 TABLE 8 Nucleic acid SNPs SNP position on Alternative Previously nucleotide sequence nucleic acid known SNP? 119 C -> T No 120 A -> T No 1062 A -> G Yes 1120 C -> No 1297 G -> T Yes 1501 A -> G Yes 1824 G -> A No 2036 A -> C No 2036 A -> G No 2095 A -> C No 2242 A -> C No 2245 A -> C No 189 C -> No 2250 A -> T Yes 2339 C -> A Yes 276 G -> A Yes 338 T -> No 424 G -> No 546 A -> G No 702 C -> T No 844 A -> G No 930 C -> T Yes

[0697] Variant protein T10888_PEA.sub.--1_P4 (SEQ ID NO:15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA.sub.--1_T4 (SEQ ID NO:2). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0698] Comparison report between T10888_PEA.sub.--1_P4 (SEQ ID NO:15) and CEA6_HUMAN SEQ ID NO:13):

[0699] 1. An isolated chimeric polypeptide encoding for T10888_PEA.sub.--1_P4 (SEQ ID NO:15), comprising a first amino acid sequence being at least 90% homologous to TABLE-US-00100 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL

corresponding to amino acids 1-234 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-234 of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000) corresponding to amino acids 235-256 of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0700] 2. An isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000) in T10888_PEA.sub.--1_P4 (SEQ ID NO:15).

[0701] Comparison report between T10888_PEA.sub.--1_P4 (SEQ ID NO:15) and Q13774 (SEQ ID NO:829):

[0702] 1. An isolated chimeric polypeptide encoding for T10888_PEA.sub.--1_P4 (SEQ ID NO:15), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL corresponding to amino acids 1-234 of Q13774, which also corresponds to amino acids 1-234 of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000) corresponding to amino acids 235-256 of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0703] 2. An isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P4 (SEQ ID NO:15), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL (SEQ ID NO:1000) in T10888_PEA.sub.--1_P4 (SEQ ID NO:15).

[0704] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0705] Variant protein T10888_PEA.sub.--1_P4 (SEQ ID NO:15 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA.sub.--1_P4 (SEQ ID NO:15) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00101 TABLE 9 Amino acid mutations SNP position(s) on amino acid Alternative sequence amino acid(s) Previously known SNP? 13 V -> No 232 N -> D No 63 I -> No 92 G -> No

[0706] Variant protein T10888_PEA.sub.--1_P4 (SEQ ID NO:15) is encoded by the following transcript(s): T10888_PEA.sub.--1_T4 (SEQ ID NO:2), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA.sub.--1_T4 (SEQ ID NO:2) is shown in bold; this coding portion starts at position 151 and ends at position 918. The transcript also the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA.sub.--1_P4 SEQ ID NO:15) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00102 TABLE 10 Nucleic acid SNPs SNP position on Alternative Previously nucleotide sequence nucleic acid known SNP? 119 C -> T No 120 A -> T No 978 C -> No 1155 G -> T Yes 1359 A -> G Yes 1682 G -> A No 1894 A -> C No 1894 A -> G No 1953 A -> C No 2100 A -> C No 2103 A -> C No 2108 A -> T Yes 189 C -> No 2197 C -> A Yes 276 G -> A Yes 338 T -> No 424 G -> No 546 A -> G No 702 C -> T No 844 A -> G No 958 G -> No

[0707] Variant protein T10888_PEA.sub.--1_P5 (SEQ ID NO:16) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA.sub.--1_T5 (SEQ ID NO:3). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0708] Comparison report between T10888_PEA.sub.--1_P5 (SEQ ID NO:16) and CEA6_HUMAN (SEQ ID NO:13):

[0709] 1. An isolated chimeric polypeptide encoding for T10888_PEA.sub.--1_P5 (SEQ ID NO:16), comprising a first amino acid sequence being at least 90% homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVSG corresponding to amino acids 1-320 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-320 of T10888_PEA.sub.--1_P5 (SEQ ID NO:16), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV (SEQ ID NO:1001) corresponding to amino acids 321-390 of T10888_PEA.sub.--1_P5 (SEQ ID NO:16), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0710] 2. An isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P5 (SEQ ID NO:16), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00103 KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF (SEQ ID NO: 1001) VVFCFLISHV in T10888_PEA_1_P5. (SEQ ID NO: 16)

[0711] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal-peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.

[0712] Variant protein T10888_PEA.sub.--1_P5 (SEQ ID NO:16) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA.sub.--1_P5 (SEQ ID NO:16) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00104 TABLE 11 Amino acid mutations SNP position(s) on amino acid Alternative sequence amino acid(s) Previously known SNP? 13 V -> No 232 N -> D No 63 I -> No 92 G -> No

[0713] Variant protein T10888_PEA.sub.--1_P5 (SEQ ID NO 16) is encoded by the following transcript(s): T10888_PEA.sub.--1_T5 (SEQ ID NO:3), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA.sub.--1_T5 (SEQ ID NO:3) is shown in bold; this coding portion starts at position 151 and ends at position 1320. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA.sub.--1_P5 (SEQ ID NO:16) sequence provides support for the deduced sequence of variant protein according to the present invention). TABLE-US-00105 TABLE 12 Nucleic acid SNPs SNP position on Alternative Previously nucleotide sequence nucleic acid known SNP? 119 C -> T No 120 A -> T No 1062 A -> G Yes 1943 C -> A Yes 2609 C -> T Yes 2647 C -> G No 2701 C -> T Yes 2841 T -> C Yes 189 C -> No 276 G -> A Yes 338 T -> No 424 G -> No 546 A -> G No 702 C -> T No 844 A -> G No 930 C -> T Yes

[0714] Variant protein T10888_PEA.sub.--1_P6 (SEQ ID NO:17) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T10888_PEA.sub.--1_T6 (SEQ ID NO:4). An alignment is given to the known protein (Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SEQ ID NO:13)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application.

[0715] Comparison report between T10888_PEA.sub.--1_P6 (SEQ ID NO:17) and CEA6_HUMAN (SEQ ID NO:13):

[0716] 1. An isolated chimeric polypeptide encoding for T10888_PEA.sub.--1_P6 (SEQ ID NO:17), comprising a first amino acid sequence being at least 90% homologous to TABLE-US-00106 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLA HNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQ NDTGFYTLQVIKSDLVNEEATGQFHVY

[0717] corresponding to amino acids 1-141 of CEA6_HUMAN (SEQ ID NO:13), which also corresponds to amino acids 1-141 of T10888_PEA.sub.--1_P6 (SEQ ID NO:17), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TABLE-US-00107 (SEQ ID NO: 1002) REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI

[0718] corresponding to amino acids 142-183 of T10888_PEA.sub.--1_P6 (SEQ ID NO:17), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0719] 2. An isolated polypeptide encoding for a tail of T10888_PEA.sub.--1_P6 (SEQ ID NO:17), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00108 (SEQ ID NO: 1002) REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI (SEQ ID NO: 17) in T10888_PEA_1_P6.

[0720] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0721] Variant protein T10888_PEA.sub.--1_P6 (SEQ ID NO:17) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA.sub.--1_P6 (SEQ ID NO:17) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00109 TABLE 13 Amino acid mutations SNP position(s) on amino acid Alternative sequence amino acid(s) Previously known SNP? 13 V -> No 63 I -> No 92 G -> No

[0722] Variant protein T10888_PEA.sub.--1_P6 (SEQ ID NO:17) is encoded by the following transcript(s): T10888_PEA.sub.--1_T6 (SEQ ID NO:4), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA.sub.--1_T6 (SEQ ID NO:4) is shown in bold; this coding portion starts at position 151 and ends at position 699. The transcript also as the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA.sub.--1_P6 (SEQ ID NO:17) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00110 TABLE 14 Nucleic acid SNPs SNP position on Alternative Previously nucleotide sequence nucleic acid known SNP? 119 C -> T No 120 A -> T No 189 C -> No 276 G -> A Yes 338 T -> No 424 G -> No 546 A -> G No

[0723] As noted above, cluster T10888 features 8 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

[0724] Segment cluster T10888_PEA.sub.--1_node.sub.--11 (SEQ ID NO:5) according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA.sub.--1_T1 (SEQ ID NO:1) and T10888_PEA.sub.--1_T5 (SEQ ID NO:3). Table 15 below describes the starting and ending position of this segment on each transcript. TABLE-US-00111 TABLE 15 Segment location on transcripts Segment Segment Transcript name starting position ending position T10888_PEA_1_T1 (SEQ ID 854 1108 NO: 1) T10888_PEA_1_T5 (SEQ ID 854 1108 NO: 3)

[0725] Segment cluster T10888_PEA.sub.--1_node.sub.--12 (SEQ ID NO:6) according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA.sub.--1_T5 (SEQ ID NO:3). Table 16 below describes the starting and ending position of this segment on each transcript. TABLE-US-00112 TABLE 16 Segment location on transcripts Segment Segment Transcript name starting position ending position T10888_PEA_1_T5 (SEQ ID 1109 3004 NO: 3)

[0726] Segment cluster T10888_PEA.sub.--1_node.sub.--17 (SEQ ID NO:7) according to the present invention is supported by 160 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA.sub.--1_T1 (SEQ ID NO:1) and T10888_PEA.sub.--1_T4 (SEQ ID NO:2). Table 17 below describes the starting and ending position of this segment on each transcript. TABLE-US-00113 TABLE 17 Segment location on transcripts Segment Segment Transcript name starting position ending position T10888_PEA_1_T1 (SEQ ID 1109 2518 NO: 1) T10888_PEA_1_T4 (SEQ ID 967 2376 NO: 2)

[0727] Segment cluster T10888_PEA.sub.--1_node.sub.--4 (SEQ ID NO:8) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA.sub.--1_T1 (SEQ ID NO:1), T10888_PEA.sub.--1_T4 (SEQ ID NO:2), T10888_PEA.sub.--1_T5 (SEQ ID NO:3) and T10888_PEA.sub.--1_T6 (SEQ ID NO:4). Table 18 below describes the starting and ending position of this segment on each transcript. TABLE-US-00114 TABLE 18 Segment location on transcripts Segment Segment Transcript name starting position ending position T10888_PEA_1_T1 (SEQ ID 1 214 NO: 1) T10888_PEA_1_T4 (SEQ ID 1 214 NO: 2) T10888_PEA_1_T5 (SEQ ID 1 214 NO: 3) T10888_PEA_1_T6 (SEQ ID 1 214 NO: 4)

[0728] Segment cluster T10888_PEA.sub.--1_node.sub.--6 (SEQ ID NO:9) according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA.sub.--1_T1 (SEQ ID NO:1), T10888_PEA.sub.--1_T4 (SEQ ID NO:2), T10888_PEA.sub.--1_T5 (SEQ ID NO:3) and T10888_PEA.sub.--1_T6 (SEQ ID NO:4). Table 19 below describes the starting and ending position of this segment on each transcript. TABLE-US-00115 TABLE 19 Segment location on transcripts Segment Segment Transcript name starting position ending position T10888_PEA_1_T1 (SEQ ID 215 574 NO: 1) T10888_PEA_1_T4 (SEQ ID 215 574 NO: 2) T10888_PEA_1_T5 (SEQ ID 215 574 NO: 3) T10888_PEA_1_T6 (SEQ ID 215 574 NO: 4)

[0729] Segment cluster T10888_PEA.sub.--1_node.sub.--7 (SEQ ID NO:10) according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA.sub.--1_T6 (SEQ ID NO:4). Table 20 below describes the starting and ending position of this segment on each transcript. TABLE-US-00116 TABLE 20 Segment location on transcripts Segment Segment Transcript name starting position ending position T10888_PEA_1_T6 (SEQ ID 575 1410 NO: 4)

[0730] Segment cluster T10888_PEA.sub.--1_node.sub.--9 (SEQ ID NO:11) according to the present invention is supported by 72 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA.sub.--1_T1 (SEQ ID NO:1), T10888_PEA.sub.--1_T4 (SEQ ID NO:2) and T10888_PEA.sub.--1_T5 (SEQ ID NO:3). Table 21 below describes the starting and ending position of this segment on each transcript. TABLE-US-00117 TABLE 21 Segment location on transcripts Segment Segment Transcript name starting position ending position T10888_PEA_1_T1 (SEQ ID 575 853 NO: 1) T10888_PEA_1_T4 (SEQ ID 575 853 NO: 2) T10888_PEA_1_T5 (SEQ ID 575 853 NO: 3)

[0731] According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

[0732] Segment cluster T10888_PEA.sub.--1_node.sub.--15 (SEQ ID NO:12) according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA.sub.--1_T4 (SEQ ID NO:2). Table 22 below describes the starting and ending position of this segment on each transcript. TABLE-US-00118 TABLE 22 Segment location on transcripts Segment Segment Transcript name starting position ending position T10888_PEA_1_T4 (SEQ ID 854 966 NO: 2)

[0733] Variant protein alignment to the previously known protein:

[0734] Sequence name: /tmp/tM4EgaoKvm/vuztUrlRc7:CEA6_HUMAN (SEQ ID NO:13).

[0735] Sequence documentation:

[0736] Alignment of: T10888_PEA.sub.--1_P2 (SEQ ID NO:14).times.CEA6_HUMAN (SEQ ID NO:13)

[0737] Alignment segment 1/1: TABLE-US-00119 Quality: 3163.00 Escore: 0 Matching length: 319 Total length: 319 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[0738] Alignment: TABLE-US-00120 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 . . . . . 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 . . . . . 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 . . . . . 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 . . . . . 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 . . . . . 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 . 301 AHNSATGLNRTTVTMITVS 319 ||||||||||||||||||| 301 AHNSATGLNRTTVTMITVS 319

[0739] Sequence name: /tmp/Yjl1gj7TCe/PgdufzLOlW:CEA6_HUMAN (SEQ ID NO:13)

[0740] Sequence documentation:

[0741] Alignment of: T10888_PEA.sub.--1_P4 (SEQ ID NO:15).times.CEA6_HUMAN (SEQ ID NO:13).

[0742] Alignment segment 1/1: TABLE-US-00121 Quality: 2310.00 Escore: 0 Matching length: 234 Total length: 234 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[0743] Alignment: TABLE-US-00122 . . . . . 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 . . . . . 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 . . . . . 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATCQFHVYPELPKPSIS 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 . . . . . 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 . . . 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234 |||||||||||||||||||||||||||||||||| 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234

[0744] Sequence name: /tmp/Yjl1gj7TCe/PgdufzLOlW:Q13774

[0745] Sequence documentation:

[0746] Alignment of: T10888_PEA.sub.--1_P4 (SEQ ID NO:15).times.Q13774.

[0747] Alignment segment 1/1: TABLE-US-00123 Quality: 2310.00 Escore: 0 Matching length: 234 Total length: 234 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[0748] Alignment: TABLE-US-00124 . . . . . 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 . . . . . 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 . . . . . 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 . . . . . 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 . . . 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234 |||||||||||||||||||||||||||||||||| 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234

[0749] Sequence name: /tmp/x5xDBacdpj/rTXRGepv3y:CEA6_HUMAN (SEQ ID NO:13)

[0750] Sequence documentation:

[0751] Alignment of: T10888_PEA.sub.--1_P5 (SEQ ID NO:16).times.CEA6_HUMAN (SEQ ID NO:13).

[0752] Alignment segment 1/1: TABLE-US-00125 Quality: 3172.00 Escore: 0 Matching length: 320 Total length: 320 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[0753] Alignment: TABLE-US-00126 . . . . . 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 . . . . . 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 . . . . . 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 . . . . . 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 . . . . . 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 . . . . . 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 . . 301 AHNSATGLNRTTVTMITVSG 320 |||||||||||||||||||| 301 AHNSATGLNRTTVTMITVSG 320

[0754] Sequence name: /tmp/VAhvYFeatq/QNEM573uCo:CEA6_HUMAN (SEQ ID NO:13)

[0755] Sequence documentation:

[0756] Alignment of: T10888_PEA.sub.--1_P6 (SEQ ID NO:17).times.CEA6_HUMAN (SEQ ID NO:13).

[0757] Alignment segment 1/1: TABLE-US-00127 Quality: 1393.00 Escore: 0 Matching length: 143 Total length: 143 Matching Percent 99.30 Matching Percent Identity: 99.30 Similarity: Total Percent Similarity: 99.30 Total Percent Identity: 99.30 Gaps: 0

[0758] Alignment: TABLE-US-00128 . . . . . 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 . . . . . 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 . . . . 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYRE 143 ||||||||||||||||||||||||||||||||||||||||| | 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPE 143

[0759] Alignment of: T10888_PEA.sub.--1_P6 (SEQ ID NO:17).times.CEA6_HUMAN (SEQ ID NO:13).

[0760] Alignment segment 1/1: TABLE-US-00129 Quality: 101.00 Escore: 0 Matching length: 141 Total length: 183 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 77.05 Total Percent Identity: 77.05 Gaps: 1

[0761] Alignment: TABLE-US-00130 . . . . . 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 . . . . . 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 . . . . . 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYREYFHMTSG 150 ||||||||||||||||||||||||||||||||||||||||| 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVY......... 141 . . . 151 CWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI 183 141 ................................. 141

Expression of CEA6_HUMAN Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 (T10888) Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T10888 junc11-17 in Normal and Cancerous Breast Tissues

[0762] Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by or according to junc11-17, T10888junc11-17 (SEQ ID NO:832) amplicon(s) and T10888junc11-17F (SEQ ID NO:830) and T10888junc11-17R primers was measured by real time PCR. In parallel the expression of four housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon--PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID NO:930); amplicon--HPRT1-amplicon (SEQ ID NO:933)), and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:922Q; amplicon--SDHA-amplicon (SEQ ID NO:925)), G6PD (GenBank Accession No. NM.sub.--000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67 Table 1, "Tissue samples in testing panel", above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

[0763] FIG. 7 is a histogram showing over expression of the above-indicated CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested, is indicated in the bottom.

[0764] As is evident from FIG. 7, the expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 56-60, 63-67 Table 1, "Tissue samples in testing panel"). Notably an over-expression of at least 5 fold was found in 19 out of 28 adenocarcinoma samples.

[0765] Statistical analysis was applied to verify the significance of these results, as described below.

[0766] The P value for the difference in the expression levels of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 2.00E-03.

[0767] Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 8.44E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

[0768] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T10888junc11-17F (SEQ ID NO:830) forward primer; and T10888junc11-17R reverse primer.

[0769] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: T10888junc11-17. TABLE-US-00131 T10888junc11-17F (SEQ ID NO: 830) CCAGCAATCCACACAAGAGCT T10888junc11-17R (SEQ ID NO: 831) CAGGGTCTGGTCCAATCAGAG T10888junc11-17 (SEQ ID NO: 832) CCAGCAATCCACACAAGAGCTCTTTATCCCCAACATCACTGTGAATAATAGC GGATCCTATATGTGCCAAGCCCATAACTCAGCCACTGGCCTCAATAGGACCACAGT CACGATGATCACAGTCTCTGATTGGACCAGACCCTG

Expression of CEA6_HUMAN Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6T10888 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T10888junc11-17 (SEQ ID NO:832) in Different Normal Tissues

[0770] Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by or according to T10888 junc11-17 amplicon(s) (SEQ ID NO:832) and T10888 junc11-17F (SEQ ID NO:830) and T10888 junc11-17R (SEQ ID NO:831) was measured by real time PCR. In parallel the expression of four housekeeping genes--RPL19 (GenBank Accession No. NM.sub.--000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM.sub.--003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon--Ubiquitin-amplicon (SEQ ID NO:945 ) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:922); amplicon--SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20, Table 2 "Tissue samples in normal panel" above), to obtain a value of relative expression of each sample relative to median of the ovary samples. Primers and amplicon are as above.

[0771] The results are presented in FIG. 8, demonstrating the expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 T10888 transcripts, which are detectable by amplicon as depicted in sequence name T10888junc11-17 (SEQ ID NO:832), in different normal tissues.

Description for Cluster T39971

[0772] Cluster T39971 features 4 transcript(s) and 28 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. TABLE-US-00132 TABLE 1 Transcripts of interest Transcript Name Sequence ID No. T39971_T10 18 T39971_T12 19 T39971_T16 20 T39971_T5 21

[0773] TABLE-US-00133 TABLE 2 Segments of interest Segment Name Sequence ID No. T39971_node_0 22 T39971_node_18 23 T39971_node_21 24 T39971_node_22 25 T39971_node_23 26 T39971_node_31 27 T39971_node_33 28 T39971_node_7 29 T39971_node_1 30 T39971_node_10 31 T39971_node_11 32 T39971_node_12 33 T39971_node_15 34 T39971_node_16 35 T39971_node_17 36 T39971_node_26 37 T39971_node_27 38 T39971_node_28 39 T39971_node_29 40 T39971_node_3 41 T39971_node_30 42 T39971_node_34 43 T39971_node_35 44 T39971_node_36 45 T39971_node_4 46 T39971_node_5 47 T39971_node_8 48 T39971_node_9 49

[0774] TABLE-US-00134 TABLE 3 Proteins of interest Protein Name Sequence ID No. T39971_P6 51 T39971_P9 52 T39971_P11 53 T39971_P12 54

[0775] These sequences are variants of the known protein Vitronectin precursor (SwissProt accession identifier VTNC_HUMAN; known also according to the synonyms Serum spreading factor; S-protein; V75), SEQ ID NO:50, referred to herein as the previously known protein.

[0776] Protein Vitronectin precursor (SEQ ID NO:50) is known or believed to have the following function(s): Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interacts with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway. The sequence for protein Vitronectin precursor is given at the end of the application, as "Vitronectin precursor amino acid sequence" (SEQ ID NO:50). Known polymorphisms for this sequence are as shown in Table 4. TABLE-US-00135 TABLE 4 Amino acid mutations for Known Protein SNP position(s) on amino acid sequence Comment 122 A -> S. /FTId = VAR_012983. 268 R -> Q. /FTId = VAR_012984. 400 T -> M. /FTId = VAR_012985. 50 C -> N 225 S -> N 366 A -> T

[0777] Protein Vitronectin precursor (SEQ ID NO:50) localization is believed to be Extracellular.

[0778] The previously known protein also has the following indication(s) and/or potential therapeutic use(s): Cancer, melanoma. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Alphavbeta3 integrin antagonist; Apoptosis agonist. A therapeutic role for a protein represented by the cluster has been predicted. The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be used for a potential therapeutic indication: Anticancer.

[0779] The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: immune response; cell adhesion, which are annotation(s) related to Biological Process; protein binding; heparin binding, which are annotation(s) related to Molecular Function; and extracellular space, which are annotation(s) related to Cellular Component.

[0780] The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

[0781] Cluster T39971 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the right hand column of the table and the numbers on the y-axis of FIG. 9 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

[0782] Overall, the following results were obtained as shown with regard to the histograms in FIG. 9 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: liver cancer, lung malignant tumors and pancreas carcinoma. TABLE-US-00136 TABLE 5 Normal tissue distribution Name of Tissue Number adrenal 60 bladder 0 Bone 0 Brain 9 Colon 0 epithelial 79 general 29 Liver 2164 Lung 0 lymph nodes 0 breast 0 pancreas 0 prostate 0 Skin 0 uterus 0

[0783] TABLE-US-00137 TABLE 6 P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 6.9e-01 7.4e-01 2.0e-02 2.3 5.3e-02 1.8 bladder 5.4e-01 6.0e-01 5.6e-01 1.8 6.8e-01 1.5 Bone 1 6.7e-01 1 1.0 7.0e-01 1.4 Brain 8.0e-01 8.6e-01 3.0e-01 1.9 5.3e-01 1.2 Colon 4.2e-01 4.8e-01 7.0e-01 1.6 7.7e-01 1.4 epithelial 6.6e-01 5.7e-01 1.0e-01 0.8 8.7e-01 0.6 general 5.1e-01 3.8e-01 9.2e-08 1.6 8.3e-04 1.3 Liver 1 6.7e-01 2.3e-03 0.3 1 0.2 Lung 2.4e-01 9.1e-02 1.7e-01 4.3 8.1e-03 5.0 lymph nodes 1 5.7e-01 1 1.0 5.8e-01 2.3 breast 1 6.7e-01 1 1.0 8.2e-01 1.2 pancreas 9.5e-02 1.8e-01 1.5e-11 6.5 8.2e-09 4.6 prostate 7.3e-01 6.0e-01 6.7e-01 1.5 5.6e-01 1.7 Skin 1 4.4e-01 1 1.0 6.4e-01 1.6 uterus 5.0e-01 2.6e-01 1 1.1 8.0e-01 1.4

[0784] As noted above, cluster T39971 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Vitronectin precursor (SEQ ID NO:50). A description of each variant protein according to the present invention is now provided.

[0785] Variant protein T39971_P6 (SEQ ID NO:51) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T5 (SEQ ID NO:21). An alignment is given to the known protein (Vitronectin precursor (SEQ ID NO:50)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0786] Comparison report between T39971_P6 (SEQ ID NO:51) and VTNC_HUMAN (SEQ ID NO:50):

[0787] 1. An isolated chimeric polypeptide encoding for T39971_P6 (SEQ ID NO:51), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG corresponding to amino acids 1-276 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 1-276 of T39971_P6 (SEQ ID NO:51),and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TQGVVGD (SEQ ID NO:1003) corresponding to amino acids 277-283 of T39971_P6 (SEQ ID NO:51), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0788] 2. An isolated polypeptide encoding for a tail of T39971_P6 (SEQ ID NO:51), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TQGVVGD (SEQ ID NO:1003) in T39971_P6 (SEQ ID NO:51).

[0789] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0790] Variant protein T39971_P6 (SEQ ID NO:51) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P6 (SEQ ID NO:51) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00138 TABLE 7 Amino acid mutations SNP position(s) on amino acid Alternative sequence amino acid(s) Previously known SNP? 122 A -> S Yes 145 G -> No 268 R -> Q Yes 280 V -> A Yes 180 C -> No 180 C -> W No 192 Y -> No 209 A -> No 211 T -> No 267 G -> No 267 G -> A No 268 R -> No

[0791] Variant protein T39971_P6 (SEQ ID NO:51) is encoded by the following transcript(s): T39971_T5 (SEQ ID NO:21), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T5 (SEQ ID NO:21) is shown in bold; this coding portion starts at position 756 and ends at position 1604. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P6 (SEQ ID NO:51) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00139 TABLE 8 Nucleic acid SNPs SNP position on nucleotide Alternative sequence nucleic acid Previously known SNP? 417 G -> C Yes 459 T -> C Yes 1387 C -> No 1406 -> A No 1406 -> G No 1555 G -> No 1555 G -> C No 1558 G -> No 1558 G -> A Yes 1594 T -> C Yes 1642 T -> C Yes 1770 C -> T Yes 529 G -> T Yes 1982 A -> G No 2007 G -> No 2029 T -> C No 2094 T -> C No 2117 C -> G No 2123 C -> T Yes 2152 C -> T Yes 2182 G -> T No 2185 A -> C No 2297 T -> C Yes 1119 G -> T Yes 2411 G -> No 2411 G -> T No 2487 T -> C Yes 1188 G -> No 1295 C -> No 1295 C -> G No 1324 -> T No 1331 C -> No 1381 C -> No

[0792] Variant protein T39971_P9 (SEQ ID NO:52) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T10 (SEQ ID NO:18). An alignment is given to the known protein (Vitronectin precursor (SEQ ID NO:50)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0793] Comparison report between T39971_P9 (SEQ ID NO:52) and VTNC_HUMAN (SEQ ID NO:50):

[0794] 1. An isolated chimeric polypeptide encoding for T39971_P9 (SEQ ID NO:52), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRT corresponding to amino acids 1-325 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 1-325 of T39971_P9 (SEQ ID NO:52), and a second amino acid sequence being at least 90% homologous to SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNONSRRPSRATWLSLFSSEESNLGA NNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLRTRRVDTVDPPYPRSIAQYWLGC PAPGHL corresponding to amino acids 357-478 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 326-447 of T39971_P9 (SEQ ID NO:52), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0795] 2. An isolated chimeric polypeptide encoding for an edge portion of T39971_P9 (SEQ ID NO:52), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TS, having a structure as follows: a sequence starting from any of amino acid numbers 325-x to 325; and ending at any of amino acid numbers 326+((n-2)-x), in which x varies from 0 to n-2.

[0796] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0797] Variant protein T39971_P9 (SEQ ID NO:52) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P9 (SEQ ID NO:52) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00140 TABLE 9 Amino acid mutations SNP position(s) on amino acid Alternative sequence amino acid(s) Previously known SNP? 122 A -> S Yes 145 G -> No 268 R -> Q Yes 328 M -> T No 350 S -> P No 369 T -> M Yes 379 S -> I No 380 N -> T No 180 C -> No 180 C -> W No 192 Y -> No 209 A -> No 211 T -> No 267 G -> No 267 G -> A No 268 R -> No

[0798] Variant protein T39971_P9 (SEQ ID NO:52) is encoded by the following transcript(s): T39971_T10 (SEQ ID NO:18), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T10 (SEQ ID NO:18) is shown in bold; this coding portion starts at position 756 and ends at position 2096. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P9 (SEQ ID NO:52) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00141 TABLE 10 Nucleic acid SNPs SNP position on nucleotide Alternative sequence nucleic acid Previously known SNP? 417 G -> C Yes 459 T -> C Yes 1387 C -> No 1406 -> A No 1406 -> G No 1555 G -> No 1555 G -> C No 1558 G -> No 1558 G -> A Yes 1738 T -> C No 1803 T -> C No 1826 C -> G No 529 G -> T Yes 1832 C -> T Yes 1861 C -> T Yes 1891 G -> T No 1894 A -> C No 2006 T -> C Yes 2120 G -> No 2120 G -> T No 2196 T -> C Yes 1119 G -> T Yes 1188 G -> No 1295 C -> No 1295 C -> G No 1324 -> T No 1331 C -> No 1381 C -> No

[0799] Variant protein T39971_P11 (SEQ ID NO:53) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T12 (SEQ ID NO:19). An alignment is given to the known protein (Vitronectin precursor (SEQ ID NO:50)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0800] Comparison report between T39971_P11 (SEQ ID NO:53) and VTNC_HUMAN (SEQ ID NO:50):

[0801] 1. An isolated chimeric polypeptide encoding for T39971_P11 (SEQ ID NO:53), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1-326 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 1-326 of T39971_P11 (SEQ ID NO:53), and a second amino acid sequence being at least 90% homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 327-363 of T39971_P11 (SEQ ID NO:53), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0802] 2. An isolated chimeric polypeptide encoding for an edge portion of T39971_P11 (SEQ ID NO:53), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327+((n-2)-x), in which x varies from 0 to n-2.

[0803] Comparison report between T39971_P11 (SEQ ID NO:53) and Q9BSH7 (SEQ ID NO:833):

[0804] 1. An isolated chimeric polypeptide encoding for T39971_P11 (SEQ ID NO:53), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGV LDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE CEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids 1-326 of Q9BSH7, which also corresponds to amino acids 1-326 of T39971_P11 (SEQ ID NO:53), and a second amino acid sequence being at least 90% homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids 442-478 of Q9BSH7, which also corresponds to amino acids 327-363 of T39971_P11 (SEQ ID NO:53), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0805] 2. An isolated chimeric polypeptide encoding for an edge portion of T39971_P11 (SEQ ID NO:53), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise SD, having a structure as follows: a sequence starting from any of amino acid numbers 326-x to 326; and ending at any of amino acid numbers 327+((n-2)-x), in which x varies from 0 to n-2.

[0806] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0807] Variant protein T39971_P11 (SEQ ID NO:53) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P11 (SEQ ID NO:53) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00142 TABLE 11 Amino acid mutations SNP position(s) on amino acid Alternative sequence amino acid(s) Previously known SNP? 122 A -> S Yes 145 G -> No 268 R -> Q Yes 180 C -> No 180 C -> W No 192 Y -> No 209 A -> No 211 T -> No 267 G -> No 267 G -> A No 268 R -> No

[0808] Variant protein T39971_P11 (SEQ ID NO:53) is encoded by the following transcript(s): T39971_T12 (SEQ ID NO:19), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T12 (SEQ ID NO:19) is shown in bold; this coding portion starts at position 756 and ends at position 1844. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P11 (SEQ ID NO:53) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00143 TABLE 12 Nucleic acid SNPs SNP position on nucleotide Alternative sequence nucleic acid Previously known SNP? 417 G -> C Yes 459 T -> C Yes 1387 C -> No 1406 -> A No 1406 -> G No 1555 G -> No 1555 G -> C No 1558 G -> No 1558 G -> A Yes 1754 T -> C Yes 1868 G -> No 1868 G -> T No 529 G -> T Yes 1944 T -> C Yes 1119 G -> T Yes 1188 G -> No 1295 C -> No 1295 C -> G No 1324 -> T No 1331 C -> No 1381 C -> No

[0809] Variant protein T39971_P12 (SEQ ID NO:54) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T39971_T16 (SEQ ID NO:20). An alignment is given to the known protein (Vitronectin precursor (SEQ ID NO:50)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0810] Comparison report between T39971_P12 (SEQ ID NO:54) and VTNC_HUMAN (SEQ ID NO:50):

[0811] 1. An isolated chimeric polypeptide encoding for T39971_P12 (SEQ ID NO:54), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1-223 of VTNC_HUMAN (SEQ ID NO:50), which also corresponds to amino acids 1-223 of T39971_P12 (SEQ ID NO:54), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) corresponding to amino acids 224-238 of T39971_P12 (SEQ ID NO:54), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0812] 2. An isolated polypeptide encoding for a tail of T39971_P12 (SEQ ID NO:54), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) in T39971_P12 (SEQ ID NO:54).

[0813] Comparison report between T39971_P12 (SEQ ID NO:54) and Q9BSH7:

[0814] 1. An isolated chimeric polypeptide encoding for T39971_P12 (SEQ ID NO:54), comprising a first amino acid sequence being at least 90% homologous to MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAEC KPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPV LKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFR GQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKTYLFK corresponding to amino acids 1-223 of Q9BSH7, which also corresponds to amino acids 1-223 of T39971_P12 (SEQ ID NO:54), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) corresponding to amino acids 224-238 of T39971_P12 (SEQ ID NO:54), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0815] 2. An isolated polypeptide encoding for a tail of T39971_P12 (SEQ ID NO:54), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO:1004) in T39971_P12 (SEQ ID NO:54).

[0816] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0817] Variant protein T39971_P12 (SEQ ID NO:54) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P 12 (SEQ ID NO:54) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00144 TABLE 13 Amino acid mutations SNP position(s) on amino acid Alternative sequence amino acid(s) Previously known SNP? 122 A -> S Yes 145 G -> No 180 C -> No 180 C -> W No 192 Y -> No 209 A -> No 211 T -> No

[0818] Variant protein T39971_P12 (SEQ ID NO:54) is encoded by the following transcript(s): T39971_T16 (SEQ ID NO:20), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T39971_T16 (SEQ ID NO:20) is shown in bold; this coding portion starts at position 756 and ends at position 1469. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T39971_P12 (SEQ ID NO:54) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00145 TABLE 14 Nucleic acid SNPs SNP position on nucleotide Alternative sequence nucleic acid Previously known SNP? 417 G -> C Yes 459 T -> C Yes 1387 C -> No 1406 -> A No 1406 -> G No 529 G -> T Yes 1119 G -> T Yes 1188 G -> No 1295 C -> No 1295 C -> G No 1324 -> T No 1331 C -> No 1381 C -> No

[0819] As noted above, cluster T39971 features 28 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

[0820] Segment cluster T39971_node.sub.--0 (SEQ ID NO:22) according to the present invention is supported by 76 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T1 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 15 below describes the starting and ending position of this segment on each transcript. TABLE-US-00146 TABLE 15 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1 810 T39971_T12 (SEQ ID NO: 19) 1 810 T39971_T16 (SEQ ID NO: 20) 1 810 T39971_T5 (SEQ ID NO: 21) 1 810

[0821] Segment cluster T39971_node.sub.--18 (SEQ ID NO:23) according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T16 (SEQ ID NO:20). Table 16 below describes the starting and ending position of this segment on each transcript. TABLE-US-00147 TABLE 16 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T16 (SEQ ID NO: 20) 1425 1592

[0822] Segment cluster T39971_node.sub.--21 (SEQ ID NO:24) according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 17 below describes the starting and ending position of this segment on each transcript. TABLE-US-00148 TABLE 17 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1425 1581 T39971_T12 (SEQ ID NO: 19) 1425 1581 T39971_T5 (SEQ ID NO: 21) 1425 1581

[0823] Segment cluster T39971_node.sub.--22 (SEQ ID NO:25) according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T5 (SEQ ID NO:21). Table 18 below describes the starting and ending position of this segment on each transcript. TABLE-US-00149 TABLE 18 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T5 (SEQ ID NO: 21) 1582 1779

[0824] Segment cluster T39971_node.sub.--23 (SEQ ID NO:26) according to the present invention is supported by 101 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 19 below describes the starting and ending position of this segment on each transcript. TABLE-US-00150 TABLE 19 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1582 1734 T39971_T12 (SEQ ID NO: 19) 1582 1734 T39971_T5 (SEQ ID NO: 21) 1780 1932

[0825] Segment cluster T39971_node.sub.--31 (SEQ ID NO:27) according to the present invention is supported by 94 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18) and T39971_T5 (SEQ ID NO:21). Table 20 below describes the starting and ending position of this segment on each transcript. TABLE-US-00151 TABLE 20 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1847 1986 T39971_T5 (SEQ ID NO: 21) 2138 2277

[0826] Segment cluster T39971_node.sub.--33 (SEQ ID NO:28) according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 21 below describes the starting and ending position of this segment on each transcript. TABLE-US-00152 TABLE 21 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1987 2113 T39971_T12 (SEQ ID NO: 19) 1735 1861 T39971_T5 (SEQ ID NO: 21) 2278 2404

[0827] Segment cluster T39971_node.sub.--7 (SEQ ID NO:29) according to the present invention is supported by 87 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T11 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 22 below describes the starting and ending position of this segment on each transcript. TABLE-US-00153 TABLE 22 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 940 1162 T39971_T12 (SEQ ID NO: 19) 940 1162 T39971_T16 (SEQ ID NO: 20) 940 1162 T39971_T5 (SEQ ID NO: 21) 940 1162

[0828] According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

[0829] Segment cluster T39971_node.sub.--1 (SEQ ID NO:30) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 23 below describes the starting and ending position of this segment on each transcript. TABLE-US-00154 TABLE 23 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 811 819 T39971_T12 (SEQ ID NO: 19) 811 819 T39971_T16 (SEQ ID NO: 20) 811 819 T39971_T5 (SEQ ID NO: 21) 811 819

[0830] Segment cluster T39971_node.sub.--10 (SEQ ID NO:31) according to the present invention is supported by 77 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 24 below describes the starting and ending position of this segment on each transcript. TABLE-US-00155 TABLE 24 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1189 1232 T39971_T12 (SEQ ID NO: 19) 1189 1232 T39971_T16 (SEQ ID NO: 20) 1189 1232 T39971_T5 (SEQ ID NO: 21) 1189 1232

[0831] Segment cluster T39971_node.sub.--11 (SEQ ID NO:32) according to the present invention is supported by 79 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 25 below describes the starting and ending position of this segment on each transcript. TABLE-US-00156 TABLE 25 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1233 1270 T39971_T12 (SEQ ID NO: 19) 1233 1270 T39971_T16 (SEQ ID NO: 20) 1233 1270 T39971_T5 (SEQ ID NO: 21) 1233 1270

[0832] Segment cluster T39971_node.sub.--12 (SEQ ID NO:33) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 26 below describes the starting and ending position of this segment on each transcript. TABLE-US-00157 TABLE 26 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1271 1284 T39971_T12 (SEQ ID NO: 19) 1271 1284 T39971_T16 (SEQ ID NO: 20) 1271 1284 T39971_T5 (SEQ ID NO: 21) 1271 1284

[0833] Segment cluster T39971_node.sub.--15 (SEQ ID NO:34) according to the present invention is supported by 79 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 27 below describes the starting and ending position of this segment on each transcript. TABLE-US-00158 TABLE 27 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1285 1316 T39971_T12 (SEQ ID NO: 19) 1285 1316 T39971_T16 (SEQ ID NO: 20) 1285 1316 T39971_T5 (SEQ ID NO: 21) 1285 1316

[0834] Segment cluster T39971_node.sub.--16 (SEQ ID NO:35) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 28 below describes the starting and ending position of this segment on each transcript. TABLE-US-00159 TABLE 28 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1317 1340 T39971_T12 (SEQ ID NO: 19) 1317 1340 T39971_T16 (SEQ ID NO: 20) 1317 1340 T39971_T5 (SEQ ID NO: 21) 1317 1340

[0835] Segment cluster T39971_node.sub.--17 (SEQ ID NO:36) according to the present invention is supported by 86 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 29 below describes the starting and ending position of this segment on each transcript. TABLE-US-00160 TABLE 29 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1341 1424 T39971_T12 (SEQ ID NO: 19) 1341 1424 T39971_T16 (SEQ ID NO: 20) 1341 1424 T39971_T5 (SEQ ID NO: 21) 1341 1424

[0836] Segment cluster T39971_node.sub.--26 (SEQ ID NO:37) according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T5 (SEQ ID NO:21). Table 30 below describes the starting and ending position of this segment on each transcript. TABLE-US-00161 TABLE 30 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T5 (SEQ ID NO: 21) 1933 1974

[0837] Segment cluster T39971_node.sub.--27 (SEQ ID NO:38) according to the present invention is supported by 90 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T5 (SEQ ID NO:21). Table 31 below describes the starting and ending position of this segment on each transcript. TABLE-US-00162 TABLE 31 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T5 (SEQ ID NO: 21) 1975 2025

[0838] Segment cluster T39971_node.sub.--28 (SEQ ID NO:39) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18) and T39971_T5 (SEQ ID NO:21). Table 32 below describes the starting and ending position of this segment on each transcript. TABLE-US-00163 TABLE 32 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1735 1743 T39971_T5 (SEQ ID NO: 21) 2026 2034

[0839] Segment cluster T39971_node.sub.--29 (SEQ ID NO:40) according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO 18) and T39971_T5 (SEQ ID NO:21). Table 33 below describes the starting and ending position of this segment on each transcript. TABLE-US-00164 TABLE 33 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1744 1838 T39971_T5 (SEQ ID NO: 21) 2035 2129

[0840] Segment cluster T39971_node.sub.--3 (SEQ ID NO:41) according to the present invention is supported by 78 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 34 below describes the starting and ending position of this segment on each transcript. TABLE-US-00165 TABLE 34 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 820 861 T39971_T12 (SEQ ID NO: 19) 820 861 T39971_T16 (SEQ ID NO: 20) 820 861 T39971_T5 (SEQ ID NO: 21) 820 861

[0841] Segment cluster T39971_node.sub.--30 (SEQ ID NO:42) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18) and T39971_T5 (SEQ ID NO:21). Table 35 below describes the starting and ending position of this segment on each transcript. TABLE-US-00166 TABLE 35 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 1839 1846 T39971_T5 (SEQ ID NO: 21) 2130 2137

[0842] Segment cluster T39971_node.sub.--34 (SEQ ID NO:43) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 36 below describes the starting and ending position of this segment on each transcript. TABLE-US-00167 TABLE 36 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 2114 2120 T39971_T12 (SEQ ID NO: 19) 1862 1868 T39971_T5 (SEQ ID NO: 21) 2405 2411

[0843] Segment cluster T39971_node.sub.--35 (SEQ ID NO:44) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 37 below describes the starting and ending position of this segment on each transcript. TABLE-US-00168 TABLE 37 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 2121 2137 T39971_T12 (SEQ ID NO: 19) 1869 1885 T39971_T5 (SEQ ID NO: 21) 2412 2428

[0844] Segment cluster T39971_node.sub.--36 (SEQ ID NO:45) according to the present invention is supported by 51 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19) and T39971_T5 (SEQ ID NO:21). Table 38 below describes the starting and ending position of this segment on each transcript. TABLE-US-00169 TABLE 38 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 2138 2199 T39971_T12 (SEQ ID NO: 19) 1886 1947 T39971_T5 (SEQ ID NO: 21) 2429 2490

[0845] Segment cluster T39971_node.sub.--4 (SEQ ID NO:46) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 39 below describes the starting and ending position of this segment on each transcript. TABLE-US-00170 TABLE 39 Segment location on transcripts Segment Segment Transcript name starting position ending position T39971_T10 (SEQ ID NO: 18) 862 881 T39971_T12 (SEQ ID NO: 19) 862 881 T39971_T16 (SEQ ID NO: 20) 862 881 T39971_T5 (SEQ ID NO: 21) 862 881

[0846] Segment cluster T39971_node.sub.--5 (SEQ ID NO:47) according to the present invention is supported by 80 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:2 1). Table 40 below describes the starting and ending position of this segment on each transcript. TABLE-US-00171 TABLE 40 Segment location on transcripts Segment Segment ending Transcript name starting position position T39971_T10 (SEQ ID NO: 18) 882 939 T39971_T12 (SEQ ID NO: 19) 882 939 T39971_T16 (SEQ ID NO: 20) 882 939 T39971_T5 (SEQ ID NO: 21) 882 939

[0847] Segment cluster T39971_node.sub.--8 (SEQ ID NO:48) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 41 below describes the starting and ending position of this segment on each transcript. TABLE-US-00172 TABLE 41 Segment location on transcripts Segment Segment ending Transcript name starting position position T39971_T10 (SEQ ID NO: 18) 1163 1168 T39971_T12 (SEQ ID NO: 19) 1163 1168 T39971_T16 (SEQ ID NO: 20) 1163 1168 T39971_T5 (SEQ ID NO: 21) 1163 1168

[0848] Segment cluster T39971_node.sub.--9 (SEQ ID NO:49) according to the present invention can be found in the following transcript(s): T39971_T10 (SEQ ID NO:18), T39971_T12 (SEQ ID NO:19), T39971_T16 (SEQ ID NO:20) and T39971_T5 (SEQ ID NO:21). Table 42 below describes the starting and ending position of this segment on each transcript. TABLE-US-00173 TABLE 42 Segment location on transcripts Segment Segment ending Transcript name starting position position T39971_T10 (SEQ ID NO: 18) 1169 1188 T39971_T12 (SEQ ID NO: 19) 1169 1188 T39971_T16 (SEQ ID NO: 20) 1169 1188 T39971_T5 (SEQ ID NO: 21) 1169 1188

[0849] Variant protein alignment to the previously known protein:

[0850] Sequence name: /tmp/xkraCL2OcZ/43L7YcPH7x:VTNC_HUMAN (SEQ ID NO:50)

[0851] Sequence documentation:

[0852] Alignment of: T39971_P6 (SEQ ID NO:51).times.VTNC_HUMAN (SEQ ID NO:50).

[0853] Alignment segment 1/1: TABLE-US-00174 Quality: 2774.00 Escore: 0 Matching length: 278 Total length: 278 Matching Percent 99.64 Matching Percent Identity: 99.64 Similarity: Total Percent Similarity: 99.64 Total Percent Identity: 99.64 Gaps: 0

[0854] Alignment: TABLE-US-00175 . . . . . 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 . . . . . 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 . . . . . 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 . . . . . 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 . . . . . 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 . . 251 PDNVDAALALPAHSYSGRERVYFFKGTQ 278 |||||||||||||||||||||||||| | 251 PDNVDAALALPAHSYSGRERVYFFKGKQ 278

[0855] Sequence name: /tmp/X4DeeuSlB4/yMubSR5FPs:VTNC_HUMAN (SEQ ID NO:50)

[0856] Sequence documentation:

[0857] Alignment of: T39971_P9 (SEQ ID NO:52).times.VTNC_HUMAN (SEQ ID NO:50).

[0858] Alignment segment 1/1: TABLE-US-00176 Quality: 4430.00 Escore: 0 Matching length: 447 Total length: 478 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 93.51 Total Percent Identity: 93.51 Gaps: 1

[0859] Alignment: TABLE-US-00177 . . . . . 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 . . . . . 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 . . . . . 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 . . . . . 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 . . . . . 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 . . . . . 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 . . . . . 301 VFEHFAMMQRDSWEDIFELLFWGRT......................... 325 ||||||||||||||||||||||||| 301 VFEHFAMMQRDSWEDIFELLFWGRTSAGTRQPQFISRDWHGVPGQVDAAM 350 . . . . . 326 ......SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 369 |||||||||||||||||||||||||||||||||||||||||||| 351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 400 . . . . . 370 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 419 |||||||||||||||||||||||||||||||||||||||||||||||||| 401 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 450 . . 420 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 447 |||||||||||||||||||||||||||| 451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478

[0860] Sequence name: /tmp/jvp1VtnxNy/wxNSeFVZZw:VTNC_HUMAN (SEQ ID NO:50)

[0861] Sequence documentation:

[0862] Alignment of: T39971_P11 (SEQ ID NO:53).times.VTNC_HUMAN (SEQ ID NO:50).

[0863] Alignment segment 1/1: TABLE-US-00178 Quality: 3576.00 Escore: 0 Matching length: 363 Total length: 478 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 75.94 Total Percent Identity: 75.94 Gaps: 1

[0864] Alignment: TABLE-US-00179 . . . . . 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 . . . . . 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 . . . . . 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 . . . . . 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 . . . . . 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 GIEGPIDAAFTRTNCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 . . . . . 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 . . . . . 301 VFEHFAMMQRDSWEDIFELLFWGRTS........................ 326 |||||||||||||||||||||||||| 301 VFEHFAMMQRDSWEDIFELLFWGRTSAGTRQPQFISRDWHGVPGQVDAAM 350 . . . . . 326 .................................................. 326 351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 400 . . . . . 327 .........................................DKYYRVNLR 335 ||||||||| 401 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 450 . . 336 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 363 |||||||||||||||||||||||||||| 451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478

[0865] Sequence name: /tmp/jvp1VtnxNy/wxNSeFVZZw:Q9BSH7

[0866] Sequence documentation:

[0867] Alignment of: T39971_P11 (SEQ ID NO:53).times.Q9BSH7

[0868] Alignment segment 1/1: TABLE-US-00180 Quality: 3576.00 Escore: 0 Matching length: 363 Total length: 478 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 75.94 Total Percent Identity: 75.94 Gaps: 1

[0869] Alignment: TABLE-US-00181 . . . . . 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 . . . . . 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 . . . . . 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 . . . . . 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 . . . . . 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 GIEGPIDAAFTRINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGI 250 . . . . . 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 PDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEECEGSSLSA 300 . . . . . 301 VFEHFAMMQRDSWEDIFELLFWGRTS........................ 326 |||||||||||||||||||||||||| 301 VFEHFAMMQRDSWEDIFELLFWGRTSAGTRQPQFISRDWHGVPGQVDAAM 350 . . . . . 326 .................................................. 326 351 AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAM 400 . . . . . 327 .........................................DKYYRVNLR 335 ||||||||| 401 WLSLFSSEESNLGANNYDDYRMDWLVPATCEPIQSVFFFSGDKYYRVNLR 450 . . 336 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 363 |||||||||||||||||||||||||||| 451 TRRVDTVDPPYPRSIAQYWLGCPAPGHL 478

[0870] Sequence name: /tmp/fgebv7ir4i/48bTBMziJ0:VTNC_HUMAN (SEQ ID NO:50)

[0871] Sequence documentation:

[0872] Alignment of: T39971_P12 (SEQ ID NO:54).times.VTNC_HUMAN (SEQ ID NO:50).

[0873] Alignment segment 1/1: TABLE-US-00182 Quality: 2237.00 Escore: 0 Matching length: 223 Total length: 223 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[0874] Alignment: TABLE-US-00183 . . . . . 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 . . . . . 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 . . . . . 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 . . . . . 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 . . 201 GIEGPIDAAFTRINCQGKTYLFK 223 ||||||||||||||||||||||| 201 GIEGPIDAAFTRINCQGKTYLFK 223

[0875] Sequence name: /tmp/fgebv7ir4i/48bTBMziJ0:Q9BSH7

[0876] Sequence documentation:

[0877] Alignment of: T39971_P12 (SEQ ID NO:54).times.Q9BSH7

[0878] Alignment segment 1/1: TABLE-US-00184 Quality: 2237.00 Escore: 0 Matching length: 223 Total length: 223 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[0879] Alignment: TABLE-US-00185 . . . . . 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSC 50 . . . . . 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 CTDYTAECKPQVTRGDVFTMPEDEYTVYDDGEEKNNATVHEQVGGPSLTS 100 . . . . . 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 DLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGRPQPP 150 . . . . . 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVW 200 . . 201 GIEGPIDAAFTRINCQGKTYLFK 223 ||||||||||||||||||||||| 201 GIEGPIDAAFTRINCQGKTYLFK 223

Expression of VTNC_HUMAN Vitronectin (Serum Spreading Factor, Somatomedin B, Complement S-Protein) T39971 Transcripts, Which are Detectable by Amplicon as Depicted in Sequence Name T39971 junc23-33 (SEQ ID NO:836) in Normal and Cancerous Breast Tissues

[0880] Expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts detectable by or according to junc23-33, T39971 junc23-33 amplicon (SEQ ID NO:836) and T39971 junc23-33F (SEQ ID NO:834) and T39971 junc23-33R (SEQ ID NO:835) primers was measured by real time PCR. In parallel the expression of four housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon--PBGD-amplicon (SEQ ID NO:929), HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID NO:930); amplicon--HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:922); amplicon--SDHA-amplicon (SEQ ID NO:925)), and G6PD (GenBank Accession No. NM.sub.--000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1, above, "Tissue samples in testing panel"), to obtain a value of fold differetial expression for each sample relative to median of the normal PM samples.

[0881] FIG. 10 is a histogram showing down regulation of the above-indicated VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts in cancerous breast samples relative to the normal samples.

[0882] As is evident from FIG. 10, the expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts detectable by the above amplicon in cancer samples was significantly lower than in the non-cancerous samples (Sample Nos. 56-60, 63-67 Table 1, "Tissue samples in testing panel").

[0883] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T39971 junc23-33F (SEQ ID NO:834) forward primer; and T39971 junc23-33R (SEQ ID NO:835) reverse primer.

[0884] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: T39971 junc23-33 (SEQ ID NO:836). TABLE-US-00186 T39971junc22-33F (SEQ ID NO: 834): GGGGCAGAACCTCTGACAAG T39971junc22-33R (SEQ ID NO: 835): GGGCAGCCCAGCCAGTA T39971junc22-33 amplicon (SEQ ID NO: 836): GGGGCAGAACCTCTGACAAGTACTACCGAGTCAATCTTCGCACACGGCGAGTGGAC ACTGTGGACCCTCCCTACCCACGCTCCATCGCTCAGTACTGGCTGGGCTGCCC

Expression of VTNC_HUMAN Vitronectin (Serum Spreading Factor, Somatomedin B, Complement S-Protein), Antisense to SARM1 (T23434), T39971 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T39971junc23-33 (SEQ ID NO:836) in Different Normal Tissues

[0885] Expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein), transcripts detectable by or according to T39971junc23-33 amplicon (SEQ ID NO:836) and T39971junc23-33F (SEQ ID NO:834) and T39971junc23-33R (SEQ ID NO:835) was measured by real time PCR. In parallel the expression of four housekeeping genes-RPL19 (GenBank Accession No. NM.sub.--000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM.sub.--003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon--Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:922); amplicon--SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (Sample Nos. 33-35, Table 2, "Tissue samples in normal panel" above), to obtain a value of relative expression of each sample relative to median of the breast samples. Primers and amplicon are as above.

[0886] The results are presented in FIG. 11, demonstrating the expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein), antisense to SARM1 (T23434), T39971 transcripts, which are detectable by amplicon as depicted in sequence name T39971junc23-33 (SEQ ID NO:836), in different normal tissues.

Expression of VTNC_HUMAN Vitronectin (Serum Spreading Factor, Somatomedin B, Complement S-Protein) T39971 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name T39971 Seg22 (SEQ ID NO:839) in Normal and Cancerous Breast Tissues

[0887] Expression of VTNC_HUMAN vitronectin (serum spreading factor, somatomedin B, complement S-protein) transcripts detectable by or according to seg22, T39971 seg22 (SEQ ID NO:839) amplicon(s) and primers T39971 seg22F (SEQ ID NO:837) and T39971 seg22R (SEQ ID NO:838) was measured by real time PCR. In parallel the expression of four housekeeping genes-PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon--PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID NO:930); amplicon--HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:922); amplicon--SDHA-amplicon (SEQ ID NO:925)); G6PD (GenBank Accession No. NM.sub.--000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60, 63-67, Table 1: Tissue samples in testing panel, above), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples.

[0888] In one experiment that was carried out no differential expression in the cancerous samples relative to the normal PM samples was observed. However, this may be due to a problem that is specific to this particular experiment.

[0889] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: T39971 seg22F (SEQ ID NO:837) forward primer; and T39971 seg22R (SEQ ID NO:838) reverse primer.

[0890] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: T39971 seg22 (SEQ ID NO:839). TABLE-US-00187 Forward primer T39971 seg22F: (SEQ ID NO: 837) GCAGTCTTGGATTCCTTTCACATT Reverse primer T39971 seg22R: (SEQ ID NO: 838) GAGGCTGTTGAAGTTAGGATCTCC Amplicon T39971 seg22: (SEQ ID NO: 839) GCAGTCTTGGATTCCTTTCACATTTCACTGGGGACAGGCCTCAGCATGTGCCCACCC CTGACCCCCACCTCATGCTGGGAGATCCTAACTTCAACAGCCTC

Description for Cluster Z21368

[0891] Cluster Z21368 features 7 transcript(s) and 34 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. TABLE-US-00188 TABLE 1 Transcripts of interest Transcript Name Sequence ID No. Z21368_PEA_1_T10 55 Z21368_PEA_1_T11 56 Z21368_PEA_1_T23 57 Z21368_PEA_1_T24 58 Z21368_PEA_1_T5 59 Z21368_PEA_1_T6 60 Z21368_PEA_1_T9 61

[0892] TABLE-US-00189 TABLE 2 Segments of interest Segment Name Sequence ID No. Z21368_PEA_1_node_0 62 Z21368_PEA_1_node_15 63 Z21368_PEA_1_node_19 64 Z21368_PEA_1_node_2 65 Z21368_PEA_1_node_21 66 Z21368_PEA_1_node_33 67 Z21368_PEA_1_node_36 68 Z21368_PEA_1_node_37 69 Z21368_PEA_1_node_39 70 Z21368_PEA_1_node_4 71 Z21368_PEA_1_node_41 72 Z21368_PEA_1_node_43 73 Z21368_PEA_1_node_45 74 Z21368_PEA_1_node_53 75 Z21368_PEA_1_node_56 76 Z21368_PEA_1_node_58 77 Z21368_PEA_1_node_66 78 Z21368_PEA_1_node_67 79 Z21368_PEA_1_node_69 80 Z21368_PEA_1_node_11 81 Z21368_PEA_1_node_12 82 Z21368_PEA_1_node_16 83 Z21368_PEA_1_node_17 84 Z21368_PEA_1_node_23 85 Z21368_PEA_1_node_24 86 Z21368_PEA_1_node_30 87 Z21368_PEA_1_node_31 88 Z21368_PEA_1_node_38 89 Z21368_PEA_1_node_47 90 Z21368_PEA_1_node_49 91 Z21368_PEA_1_node_51 92 Z21368_PEA_1_node_61 93 Z21368_PEA_1_node_68 94 Z21368_PEA_1_node_7 95

[0893] TABLE-US-00190 TABLE 3 Proteins of interest Protein Name Sequence ID No. Z21368_PEA_1_P2 97 Z21368_PEA_1_P5 98 Z21368_PEA_1_P15 99 Z21368_PEA_1_P16 100 Z21368_PEA_1_P22 101 Z21368_PEA_1_P23 102

[0894] These sequences are variants of the known protein Extracellular sulfatase Sulf-1 precursor (SwissProt accession identifier SUL1_HUMAN; known also according to the synonyms EC 3.1.6.-; HSulf-1), SEQ ID NO:96, referred to herein as the previously known protein.

[0895] Protein Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96) is known or believed to have the following function(s): Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin. Diminishes HSPG (heparan sulfate proteoglycans) sulfation, inhibits signaling by heparin-dependent growth factors, diminishes proliferation, and facilitates apoptosis in response to exogenous stimulation. The sequence for protein Extracellular sulfatase Sulf-1 precursor is given at the end of the application, as "Extracellular sulfatase Sulf-1 precursor amino acid sequence" (SEQ ID NO:96). Known polymorphisms for this sequence are as shown in Table 4. TABLE-US-00191 TABLE 4 Amino acid mutations for Known Protein SNP position(s) on amino acid sequence Comment 87-88 CC->AA: LOSS OF ARYLSULFATASE ACTIVITY AND LOSS OF ABILITY TO MODULATE APOPTOSIS. 49 L -> P 728 K -> R

[0896] Protein Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96) localization is believed to be Endoplasmic reticulum and Golgi stack; also localized on the cell surface (By similarity).

[0897] The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: apoptosis; metabolism; heparan sulfate proteoglycan metabolism, which are annotation(s) related to Biological Process; arylsulfatase; hydrolase, which are annotation(s) related to Molecular Function; and extracellular space; endoplasmic reticulum; Golgi apparatus, which are annotation(s) related to Cellular Component.

[0898] The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http:H/www.ncbi.nlm.nih.gov/projects/LocusLink/>.

[0899] Cluster Z21368 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the right hand column of the table and the numbers on the y-axis of FIG. 12 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

[0900] Overall, the following results were obtained as shown with regard to the histograms in FIG. 12 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma. TABLE-US-00192 TABLE 5 Normal tissue distribution Name of Tissue Number bladder 123 Bone 557 Brain 34 Colon 94 epithelial 56 general 68 head and neck 0 kidney 35 Lung 22 lymph nodes 0 breast 52 muscle 31 ovary 0 pancreas 0 prostate 44 skin 67 stomach 109 T cells 0 Thyroid 0 uterus 140

[0901] TABLE-US-00193 TABLE 6 P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bladder 5.4e-01 6.6e-01 6.4e-01 1.0 8.5e-01 0.7 bone 4.5e-01 8.2e-01 9.1e-01 0.4 1 0.3 brain 5.5e-01 7.3e-01 1.5e-01 1.5 5.0e-01 0.9 colon 1.4e-01 2.8e-01 1.0e-01 2.0 3.0e-01 1.4 epithelial 1.1e-03 1.5e-01 1.2e-07 2.1 1.0e-01 1.1 general 1.4e-05 5.3e-02 1.9e-06 1.6 6.7e-01 0.8 head and neck 2.4e-02 7.1e-02 4.6e-01 2.5 7.5e-01 1.4 kidney 8.9e-01 9.0e-01 1 0.4 1 0.4 lung 3.5e-01 4.1e-01 7.2e-03 2.6 1.0e-01 1.6 lymph nodes 7.7e-02 3.1e-01 2.3e-02 8.5 1.9e-01 3.2 breast 4.0e-01 6.1e-01 5.4e-02 2.3 3.0e-01 1.3 muscle 7.5e-02 3.5e-02 1 1.0 1.7e-01 1.7 ovary 3.8e-01 4.2e-01 2.2e-01 2.9 3.4e-01 2.2 pancreas 2.2e-02 6.9e-02 1.4e-08 6.5 1.4e-06 4.6 prostate 8.3e-01 8.9e-01 3.1e-01 1.4 5.2e-01 1.1 skin 6.1e-01 8.1e-01 6.0e-01 1.2 1 0.3 stomach 4.4e-02 5.0e-01 5.0e-01 0.8 9.7e-01 0.4 T cells 5.0e-01 6.7e-01 3.3e-01 3.1 7.2e-01 1.4 Thyroid 3.6e-01 3.6e-01 1 1.1 1 1.1 uterus 3.5e-01 7.8e-01 4.6e-01 0.9 9.1e-01 0.5

[0902] As noted above, cluster Z21368 features 7 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96). A description of each variant protein according to the present invention is now provided.

[0903] Variant protein Z21368_PEA.sub.--1_P2 (SEQ ID NO:97) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA.sub.--1_T5 (SEQ ID NO:59). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0904] Comparison report between Z21368_PEA.sub.--1_P2 (SEQ ID NO:97) and SUL1_HUMAN (SEQ ID NO:96):

[0905] 1. An isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P2 (SEQ ID NO:97), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGK LRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNO GTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQ ASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYI DKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKE AAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWN corresponding to amino acids 1-761 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-761 of Z21368_PEA.sub.--1_P2 (SEQ ID NO:97), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO:1005) corresponding to amino acids 762-790 of Z21368_PEA.sub.--1_P2 (SEQ ID NO:97), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0906] 2. An isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P2 (SEQ ID NO:97), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO:1005) in Z21368_PEA.sub.--1_P2 (SEQ ID NO:97).

[0907] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0908] Variant protein Z21368_PEA.sub.--1_P2 (SEQ ID NO:97) is encoded by the following transcript(s): Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA.sub.--1_T5 (SEQ ID NO:59) is shown in bold; this coding portion starts at position 529 and ends at position 2898.

[0909] Variant protein Z21368_PEA.sub.--1_P5 (SEQ ID NO:98) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0910] Comparison report between Z21368_PEA.sub.--1_P5 (SEQ ID NO:98) and Q7Z2W2 (SEQ ID NO:840) (SEQ ID NO:840):

[0911] 1. An isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1-57 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 1-57 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), second bridging amino acid sequence comprising A, and a third amino acid sequence being at least 90% homologous to FFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITN ESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNM DKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYT ADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDT PPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHL PKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLY ARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNOGTPKYKPRFVHTRQTRSLSVEFE GEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPT TVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKR RKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKER KEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNE THNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNOLHVQLMELRSCQGYKQCN PRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 139-871 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 59-791 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

[0912] 2. An isolated polypeptide encoding for an edge portion of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least three amino acids comprise LAF having a structure as follows (numbering according to Z21368_PEA.sub.--1_P5 (SEQ ID NO:98)): a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 59+((n-2)-x), in which x varies from 0 to n-2.

[0913] Comparison report between Z21368_PEA.sub.--1_P5 (SEQ ID NO:98) and AAH12997 (SEQ ID NO:841) (SEQ ID NO:841):

[0914] 1. An isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNOGTPKYKPRFVHTRQTRSLSVEFEGE IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNOLHVQLME (SEQ ID NO:1006) corresponding to amino acids 1-751 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), and a second amino acid sequence being at least 90% homologous to LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 1-40 of AAH12997 (SEQ ID NO:841), which also corresponds to amino acids 752-791 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0915] 2. An isolated polypeptide encoding for a head of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00194 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFF (SEQ ID NO: 1006) GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNES INYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDK HWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTAD HGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGLDTPP DVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLP KYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYA RGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGE IYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTV RVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRK PEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKE KRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME of Z21368_PEA_1_P5. (SEQ ID NO: 98)

[0916] Comparison report between Z21368_PEA.sub.--1_P5 (SEQ ID NO:98) and SUL1_HUMAN (SEQ ID NO:96):

[0917] 1. An isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL corresponding to amino acids 1-57 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-57 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), and a second amino acid sequence being at least 90% homologous to AFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLIT NESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPN MDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNMLVETGELENTYII YTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIAGL DTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEES SKNIQQSN HLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRN LYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNOGTPKYKPRFVHTRQTRSLSVE FEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGP PTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHL KRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRK KERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRT VNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNOLHVQLMELRSCQGYK QCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids 138-871 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 58-791 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0918] 2. An isolated chimeric polypeptide encoding for an edge portion of Z21368_PEA.sub.--1_P5 (SEQ ID NO:98), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise LA, having a structure as follows: a sequence starting from any of amino acid numbers 57-x to 57; and ending at any of amino acid numbers 58+((n-2)-x), in which x varies from 0 to n-2.

[0919] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0920] Variant protein Z21368_PEA.sub.--1_P5 (SEQ ID NO:98) is encoded by the following transcript(s): Z21368_PEA.sub.--1_T9 (SEQ ID NO:61), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA.sub.--1_T9 (SEQ ID NO:61) is shown in bold; this coding portion starts at position 556 and ends at position 2928.

[0921] Variant protein Z21368_PEA.sub.--1_P15 (SEQ ID NO:99) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA.sub.--1_T23 (SEQ ID NO:57). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0922] Comparison report between Z21368_PEA.sub.--1_P15 (SEQ ID NO:99) and SUL1_HUMAN (SEQ ID NO:96):

[0923] 1. An isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P15 (SEQ ID NO.99), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFL VERG corresponding to amino acids 1-416 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-416 of Z21368_PEA.sub.--1_P15 (SEQ ID NO:99).

[0924] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0925] Variant protein Z21368_PEA.sub.--1_P15 (SEQ ID NO:99) is encoded by the following transcript(s): Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA.sub.--1_T23 (SEQ ID NO:57) is shown in bold; this coding portion starts at position 691 and ends at position 1938.

[0926] Variant protein Z21368_PEA.sub.--1_P16 (SEQ ID NO:100) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA.sub.--1_T24 (SEQ ID NO:58). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0927] Comparison report between Z21368_PEA.sub.--1_P16 (SEQ ID NO:100) and SUL1_HUMAN (SEQ ID NO:96):

[0928] 1. An isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P16 (SEQ ID NO:100), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQ FSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDD SVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR corresponding to amino acids 1-397 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-397 of Z21368_PEA.sub.--1_P 16 (SEQ ID NO:100), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence CVIVPPLSQPQIH (SEQ ID NO:1007) corresponding to amino acids 398-410 of Z21368_PEA.sub.--1_P16 (SEQ ID NO:100), wherein said first and second amino acid sequnes are contiguous and in a sequential order.

[0929] 2. An isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P 16 (SEQ ID NO:100), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CVIVPPLSQPQIH (SEQ ID NO:1007) in Z21368_PEA.sub.--1_P16 (SEQ ID NO:100).

[0930] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0931] Variant protein Z21368_PEA.sub.--1_P16 (SEQ ID NO:100) is encoded by the following transcript(s): Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA.sub.--1_T24 (SEQ ID NO:58) is shown in bold; this coding portion starts at position 691 and ends at position 1920.

[0932] Variant protein Z21368_PEA.sub.--1_P22 (SEQ ID NO:101) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA.sub.--1_T10 (SEQ ID NO:55) An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0933] Comparison report between Z21368_PEA.sub.--1_P22 (SEQ ID NO:101) and SUL1_HUMAN (SEQ ID NO:96):

[0934] 1. An isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P22 (SEQ ID NO:101), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCR NGIKEKHGFDYAK corresponding to amino acids 1-188 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-188 of Z21368_PEA.sub.--1_P22 (SEQ ID NO:101), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO:1008) corresponding to amino acids 189-210 of Z21368_PEA.sub.--1_P22 (SEQ ID NO:101), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0935] 2. An isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P22 (SEQ ID NO:101), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO:1008) in Z21368_PEA.sub.--1_P22 (SEQ ID NO:101).

[0936] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0937] Variant protein Z21368_PEA.sub.--1_P22 (SEQ ID NO:101) is encoded by the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA.sub.--1_T10 (SEQ ID NO:55) is shown in bold; this coding portion starts at position 691 and ends at position 1320.

[0938] Variant protein Z21368_PEA.sub.--1_P23 (SEQ ID NO:102) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z21368_PEA.sub.--1_T10 (SEQ ID NO:56). An alignment is given to the known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID NO:96)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[0939] Comparison report between Z21368_PEA.sub.--1_P23 (SEQ ID NO:102) and Q7Z2W2 (SEQ ID NO:840):

[0940] 1. An isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1-137 of Q7Z2W2 (SEQ ID NO:840), which also corresponds to amino acids 1-137 of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH (SEQ ID NO:1009) corresponding to amino acids 138-145 of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0941] 2. An isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH (SEQ ID NO:1009) in Z21368_PEA.sub.--1_P23 (SEQ ID NO:102).

[0942] Comparison report between Z21368_PEA.sub.--1_P23 (SEQ ID NO:102) and SUL1_HUMAN (SEQ ID NO:96):

[0943] 1. An isolated chimeric polypeptide encoding for Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), comprising a first amino acid sequence being at least 90% homologous to MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSL QVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSW QAMHEPRTFAVYLNNTGYRT corresponding to amino acids 1-137 of SUL1_HUMAN (SEQ ID NO:96), which also corresponds to amino acids 1-137 of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GLLHRLNH (SEQ ID NO:1009) corresponding to amino acids 138-145 of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[0944] 2. An isolated polypeptide encoding for a tail of Z21368_PEA.sub.--1_P23 (SEQ ID NO:102), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GLLHRLNH (SEQ ID NO:1009) in Z21368_PEA.sub.--1_P23 (SEQ ID NO:102).

[0945] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[0946] Variant protein Z21368_PEA.sub.--1_P23 (SEQ ID NO:102) is encoded by the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:56), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z21368_PEA.sub.--1_T11 (SEQ ID NO:56) is shown in bold; this coding portion starts at position 691 and ends at position 1125.

[0947] As noted above, cluster Z21368 features 34 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided.

[0948] Segment cluster Z21368_PEA.sub.--1_node.sub.--0 (SEQ ID NO:62) according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 7 below describes the starting and ending position of this segment on each transcript. TABLE-US-00195 TABLE 7 Segment location on transcripts Segment Segment ending Transcript name starting position position Z21368_PEA_1_T9 (SEQ ID 1 327 NO: 61)

[0949] Segment cluster Z21368_PEA.sub.--1_node.sub.--15 (SEQ ID NO:63) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 8 below describes the starting and ending position of this segment on each transcript. TABLE-US-00196 TABLE 8 Segment location on transcripts Segment Segment ending Transcript name starting position position Z21368_PEA_1_T10 (SEQ 631 807 ID NO: 55) Z21368_PEA_1_T11 (SEQ 631 807 ID NO: 56) Z21368_PEA_1_T23 (SEQ 631 807 ID NO: 57) Z21368_PEA_1_T24 (SEQ 631 807 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 469 645 NO: 59) Z21368_PEA_1_T6 (SEQ ID 469 645 NO: 60) Z21368_PEA_1_T9 (SEQ ID 496 672 NO: 61)

[0950] Segment cluster Z21368_PEA.sub.--1_node.sub.--19 (SEQ ID NO:64) according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59) and Z21368_PEA.sub.--1_T6 (SEQ ID NO:60). Table 9 below describes the starting and ending position of this segment on each transcript. TABLE-US-00197 TABLE 9 Segment location on transcripts Segment Segment ending Transcript name starting position position Z21368_PEA_1_T10 (SEQ 863 1102 ID NO: 55) Z21368_PEA_1_T11 (SEQ 863 1102 ID NO: 56) Z21368_PEA_1_T23 (SEQ 863 1102 ID NO: 57) Z21368_PEA_1_T24 (SEQ 863 1102 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 701 940 NO: 59) Z21368_PEA_1_T6 (SEQ ID 701 940 NO: 60)

[0951] Segment cluster Z21368_PEA.sub.--1_node.sub.--2 (SEQ ID NO:65) according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59) and Z21368_PEA.sub.--1_T6 (SEQ ID NO:60). Table 10 below describes the starting and ending position of this segment on each transcript. TABLE-US-00198 TABLE 10 Segment location on transcripts Segment Segment ending Transcript name starting position position Z21368_PEA_1_T10 (SEQ 1 300 ID NO: 55) Z21368_PEA_1_T11 (SEQ 1 300 ID NO: 56) Z21368_PEA_1_T23 (SEQ 1 300 ID NO: 57) Z21368_PEA_1_T24 (SEQ 1 300 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 1 300 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1 300 NO: 60)

[0952] Segment cluster Z21368_PEA.sub.--1_node.sub.--21 (SEQ ID NO:66) according to the present invention is supported by 37 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA 1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 11 below describes the starting and ending position of this segment on each transcript. TABLE-US-00199 TABLE 11 Segment location on transcripts Segment Segment ending Transcript name starting position position Z21368_PEA_1_T10 (SEQ 1103 1254 ID NO: 55) Z21368_PEA_1_T23 (SEQ 1103 1254 ID NO: 57) Z21368_PEA_1_T24 (SEQ 1103 1254 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 941 1092 NO: 59) Z21368_PEA_1_T6 (SEQ ID 941 1092 NO: 60) Z21368_PEA_1_T9 (SEQ ID 728 879 NO: 61)

[0953] Segment cluster Z21368_PEA.sub.--1_node.sub.--33 (SEQ ID NO:67) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 12 below describes the starting and ending position of this segment on each transcript. TABLE-US-00200 TABLE 12 Segment location on transcripts Segment Segment ending Transcript name starting position position Z21368_PEA_1_T10 (SEQ 1502 1677 ID NO: 55) Z21368_PEA_1_T11 (SEQ 1424 1599 ID NO: 56) Z21368_PEA_1_T23 (SEQ 1576 1751 ID NO: 57) Z21368_PEA_1_T24 (SEQ 1576 1751 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 1414 1589 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1414 1589 NO: 60) Z21368_PEA_1_T9 (SEQ ID 1201 1376 NO: 61)

[0954] Segment cluster Z21368_PEA.sub.--1_node.sub.--36 (SEQ ID NO:68) according to the present invention is supported by 44 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 13 below describes the starting and ending position of this segment on each transcript. TABLE-US-00201 TABLE 13 Segment location on transcripts Segment Segment ending Transcript name starting position position Z21368_PEA_1_T10 (SEQ 1678 1806 ID NO: 55) Z21368_PEA_1_T11 (SEQ 1600 1728 ID NO: 56) Z21368_PEA_1_T23 (SEQ 1752 1880 ID NO: 57) Z21368_PEA_1_T24 (SEQ 1752 1880 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 1590 1718 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1590 1718 NO: 60) Z21368_PEA_1_T9 (SEQ ID 1377 1505 NO: 61)

[0955] Segment cluster Z21368_PEA.sub.--1_node.sub.--37 (SEQ ID NO:69) according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T24 (SEQ ID NO:58). Table 14 below describes the starting and ending position of this segment on each transcript. TABLE-US-00202 TABLE 14 Segment location on transcripts Segment Transcript name starting position Segment ending position Z21368_PEA_1_T24 1881 2159 (SEQ ID NO: 58)

[0956] Segment cluster Z21368_PEA.sub.--1_node.sub.--39 (SEQ ID NO:70) according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T23 (SEQ ID NO:57) and Z21368_PEA.sub.--1_T24 (SEQ ID NO:58). Table 15 below describes the starting and ending position of this segment on each transcript. TABLE-US-00203 TABLE 15 Segment location on transcripts Segment Transcript name Segment starting position ending position Z21368_PEA_1_T23 (SEQ 1938 2790 ID NO: 57) Z21368_PEA_1_T24 (SEQ 2217 3069 ID NO: 58)

[0957] Segment cluster Z21368_PEA.sub.--1_node.sub.--4 (SEQ ID NO:71) according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57) and Z21368_PEA.sub.--1_T24 (SEQ ID NO:58). Table 16 below describes the starting and ending position of this segment on each transcript. TABLE-US-00204 TABLE 16 Segment location on transcripts Segment Transcript name Segment starting position ending position Z21368_PEA_1_T10 (SEQ 301 462 ID NO: 55) Z21368_PEA_1_T11 (SEQ 301 462 ID NO: 56) Z21368_PEA_1_T23 (SEQ 301 462 ID NO: 57) Z21368_PEA_1_T24 (SEQ 301 462 ID NO: 58)

[0958] Segment cluster Z21368_PEA.sub.--1_node.sub.--41 (SEQ ID NO:72) according to the present invention is supported by 49 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 17 below describes the starting and ending position of this segment on each transcript. TABLE-US-00205 TABLE 17 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 1864 1993 ID NO: 55) Z21368_PEA_1_T11 (SEQ 1786 1915 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 1776 1905 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1776 1905 NO: 60) Z21368_PEA_1_T9 (SEQ ID 1563 1692 NO: 61)

[0959] Segment cluster Z21368_PEA.sub.--1_node.sub.--43 (SEQ ID NO:73) according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 18 below describes the starting and ending position of this segment on each transcript. TABLE-US-00206 TABLE 18 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 1994 2210 ID NO: 55) Z21368_PEA_1_T11 (SEQ 1916 2132 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 1906 2122 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1906 2122 NO: 60) Z21368_PEA_1_T9 (SEQ ID 1693 1909 NO: 61)

[0960] Segment cluster Z21368_PEA.sub.--1_node.sub.--45 (SEQ ID NO:74) according to the present invention is supported by 64 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 19 below describes the starting and ending position of this segment on each transcript. TABLE-US-00207 TABLE 19 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 2211 2466 ID NO: 55) Z21368_PEA_1_T11 (SEQ 2133 2388 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 2123 2378 NO: 59) Z21368_PEA_1_T6 (SEQ ID 2123 2378 NO: 60) Z21368_PEA_1_T9 (SEQ ID 1910 2165 NO: 61)

[0961] Segment cluster Z21368_PEA.sub.--1_node.sub.--53 (SEQ ID NO:75) according to the present invention is supported by 60 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 20 below describes the starting and ending position of this segment on each transcript. TABLE-US-00208 TABLE 20 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 2725 2900 ID NO: 55) Z21368_PEA_1_T11 (SEQ 2647 2822 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 2637 2812 NO: 59) Z21368_PEA_1_T6 (SEQ ID 2637 2812 NO: 60) Z21368_PEA_1_T9 (SEQ ID 2424 2599 NO: 61)

[0962] Segment cluster Z21368_PEA.sub.--1_node.sub.--56 (SEQ ID NO:76) according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 21 below describes the starting and ending position of this segment on each transcript. TABLE-US-00209 TABLE 21 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 2901 3043 ID NO: 55) Z21368_PEA_1_T11 (SEQ 2823 2965 ID NO: 56) Z21368_PEA_1_T9 (SEQ 2600 2742 ID NO: 61)

[0963] Segment cluster Z21368_PEA.sub.--1_node.sub.--58 (SEQ ID NO:77) according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 22 below describes the starting and ending position of this segment on each transcript. TABLE-US-00210 TABLE 22 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 3044 3167 ID NO: 55) Z21368_PEA_1_T11 (SEQ 2966 3089 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 2813 2936 NO: 59) Z21368_PEA_1_T6 (SEQ ID 2813 2936 NO: 60) Z21368_PEA_1_T9 (SEQ ID 2743 2866 NO: 61)

[0964] Segment cluster Z21368_PEA.sub.--1_node.sub.--66 (SEQ ID NO:78) according to the present invention is supported by 142 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56, Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 23 below describes the starting and ending position of this segment on each transcript. TABLE-US-00211 TABLE 23 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 3202 3789 ID NO: 55) Z21368_PEA_1_T11 (SEQ 3124 3711 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 2971 3558 NO: 59) Z21368_PEA_1_T6 (SEQ ID 2971 3558 NO: 60) Z21368_PEA_1_T9 (SEQ ID 2901 3488 NO: 61)

[0965] Segment cluster Z21368_PEA.sub.--1_node.sub.--67 (SEQ ID NO:79) according to the present invention is supported by 181 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 24 below describes the starting and ending position of this segment on each transcript. TABLE-US-00212 TABLE 24 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 3790 4374 ID NO: 55) Z21368_PEA_1_T11 (SEQ 3712 4296 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 3559 4143 NO: 59) Z21368_PEA_1_T6 (SEQ ID 3559 4143 NO: 60) Z21368_PEA_1_T9 (SEQ ID 3489 4073 NO: 61)

[0966] Segment cluster Z21368_PEA.sub.--1_node.sub.--69 (SEQ ID NO:80) according to the present invention is supported by 150 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 25 below describes the starting and ending position of this segment on each transcript. TABLE-US-00213 TABLE 25 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 4428 4755 ID NO: 55) Z21368_PEA_1_T11 (SEQ 4350 4677 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 4197 5384 NO: 59) Z21368_PEA_1_T6 (SEQ ID 4197 4524 NO: 60) Z21368_PEA_1_T9 (SEQ ID 4127 4454 NO: 61)

[0967] According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description.

[0968] Segment cluster Z21368_PEA.sub.--1_node.sub.--11 (SEQ ID NO:81) according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 26 below describes the starting and ending position of this segment on each transcript. TABLE-US-00214 TABLE 26 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 558 602 ID NO: 55) Z21368_PEA_1_T11 (SEQ 558 602 ID NO: 56) Z21368_PEA_1_T23 (SEQ 558 602 ID NO: 57) Z21368_PEA_1_T24 (SEQ 558 602 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 396 440 NO: 59) Z21368_PEA_1_T6 (SEQ ID 396 440 NO: 60) Z21368_PEA_1_T9 (SEQ ID 423 467 NO: 61)

[0969] Segment cluster Z21368_PEA.sub.--1_node.sub.--12 (SEQ ID NO:82) according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56, Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1T9 (SEQ ID NO:61). Table 27 below describes the starting and ending position of this segment on each transcript. TABLE-US-00215 TABLE 27 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 603 630 ID NO: 55) Z21368_PEA_1_T11 (SEQ 603 630 ID NO: 56) Z21368_PEA_1_T23 (SEQ 603 630 ID NO: 57) Z21368_PEA_1_T24 (SEQ 603 630 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 441 468 NO: 59) Z21368_PEA_1_T6 (SEQ ID 441 468 NO: 60) Z21368_PEA_1_T9 (SEQ ID 468 495 NO: 61)

[0970] Segment cluster Z21368_PEA.sub.--1_node.sub.--16 (SEQ ID NO:83) according to the present invention can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 28 below describes the starting and ending position of this segment on each transcript. TABLE-US-00216 TABLE 28 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 808 822 ID NO: 55) Z21368_PEA_1_T11 (SEQ 808 822 ID NO: 56) Z21368_PEA_1_T23 (SEQ 808 822 ID NO: 57) Z21368_PEA_1_T24 (SEQ 808 822 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 646 660 NO: 59) Z21368_PEA_1_T6 (SEQ ID 646 660 NO: 60) Z21368_PEA_1_T9 (SEQ ID 673 687 NO: 61)

[0971] Segment cluster Z21368_PEA.sub.--1_node.sub.--17 (SEQ ID NO:84) according to the present invention is supported by 19 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 29 below describes the starting and ending position of this segment on each transcript. TABLE-US-00217 TABLE 29 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 823 862 ID NO: 55) Z21368_PEA_1_T11 (SEQ 823 862 ID NO: 56) Z21368_PEA_1_T23 (SEQ 823 862 ID NO: 57) Z21368_PEA_1_T24 (SEQ 823 862 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 661 700 NO: 59) Z21368_PEA_1_T6 (SEQ ID 661 700 NO: 60) Z21368_PEA_1_T9 (SEQ ID 688 727 NO: 61)

[0972] Segment cluster Z21368_PEA.sub.--1_node.sub.--23 (SEQ ID NO:85) according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 30 below describes the starting and ending position of this segment on each transcript. TABLE-US-00218 TABLE 30 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T11 (SEQ 1103 1176 ID NO: 56) Z21368_PEA_1_T23 (SEQ 1255 1328 ID NO: 57) Z21368_PEA_1_T24 (SEQ 1255 1328 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 1093 1166 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1093 1166 NO: 60) Z21368_PEA_1_T9 (SEQ ID 880 953 NO: 61)

[0973] Segment cluster Z21368_PEA.sub.--1_node.sub.--24 (SEQ ID NO:86) according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 31 below describes the starting and ending position of this segment on each transcript. TABLE-US-00219 TABLE 31 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 1255 1350 ID NO: 55) Z21368_PEA_1_T11 (SEQ 1177 1272 ID NO: 56) Z21368_PEA_1_T23 (SEQ 1329 1424 ID NO: 57) Z21368_PEA_1_T24 (SEQ 1329 1424 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 1167 1262 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1167 1262 NO: 60) Z21368_PEA_1_T9 (SEQ ID 954 1049 NO: 61)

[0974] Segment cluster Z21368_PEA.sub.--1_node.sub.--30 (SEQ ID NO:87) according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 32 below describes the starting and ending position of this segment on each transcript. TABLE-US-00220 TABLE 32 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 1351 1409 ID NO: 55) Z21368_PEA_1_T11 (SEQ 1273 1331 ID NO: 56) Z21368_PEA_1_T23 (SEQ 1425 1483 ID NO: 57) Z21368_PEA_1_T24 (SEQ 1425 1483 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 1263 1321 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1263 1321 NO: 60) Z21368_PEA_1_T9 (SEQ ID 1050 1108 NO: 61)

[0975] Segment cluster Z21368_PEA.sub.--1_node.sub.--31 (SEQ ID NO:88) according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 33 below describes the starting and ending position of this segment on each transcript. TABLE-US-00221 TABLE 33 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 1410 1501 ID NO: 55) Z21368_PEA_1_T11 (SEQ 1332 1423 ID NO: 56) Z21368_PEA_1_T23 (SEQ 1484 1575 ID NO: 57) Z21368_PEA_1_T24 (SEQ 1484 1575 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 1322 1413 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1322 1413 NO: 60) Z21368_PEA_1_T9 (SEQ ID 1109 1200 NO: 61)

[0976] Segment cluster Z21368_PEA.sub.--1_node.sub.--38 (SEQ ID NO:89) according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 34 below describes the starting and ending position of this segment on each transcript. TABLE-US-00222 TABLE 34 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 1807 1863 ID NO: 55) Z21368_PEA_1_T11 (SEQ 1729 1785 ID NO: 56) Z21368_PEA_1_T23 (SEQ 1881 1937 ID NO: 57) Z21368_PEA_1_T24 (SEQ 2160 2216 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 1719 1775 NO: 59) Z21368_PEA_1_T6 (SEQ ID 1719 1775 NO: 60) Z21368_PEA_1_T9 (SEQ ID 1506 1562 NO: 61)

[0977] Segment cluster Z21368_PEA.sub.--1_node.sub.--47 (SEQ ID NO:90) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 35 below describes the starting and ending position of this segment on each transcript. TABLE-US-00223 TABLE 35 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 2467 2563 ID NO: 55) Z21368_PEA_1_T11 (SEQ 2389 2485 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 2379 2475 NO: 59) Z21368_PEA_1_T6 (SEQ ID 2379 2475 NO: 60) Z21368_PEA_1_T9 (SEQ ID 2166 2262 NO: 61)

[0978] Segment cluster Z21368_PEA.sub.--1_node.sub.--49 (SEQ ID NO 91) according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 36 below describes the starting and ending position of this segment on each transcript. TABLE-US-00224 TABLE 36 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 2564 2658 ID NO: 55) Z21368_PEA_1_T11 (SEQ 2486 2580 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 2476 2570 NO: 59) Z21368_PEA_1_T6 (SEQ ID 2476 2570 NO: 60) Z21368_PEA_1_T9 (SEQ ID 2263 2357 NO: 61)

[0979] Segment cluster Z21368_PEA.sub.--1_node.sub.--51 (SEQ ID NO:92) according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 37 below describes the starting and ending position of this segment on each transcript. TABLE-US-00225 TABLE 37 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 2659 2724 ID NO: 55) Z21368_PEA_1_T11 (SEQ 2581 2646 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 2571 2636 NO: 59) Z21368_PEA_1_T6 (SEQ ID 2571 2636 NO: 60) Z21368_PEA_1_T9 (SEQ ID 2358 2423 NO: 61)

[0980] Segment cluster Z21368_PEA.sub.--1_node.sub.--61 (SEQ ID NO:93) according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 38 below describes the starting and ending position of this segment on each transcript. TABLE-US-00226 TABLE 38 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 3168 3201 ID NO: 55) Z21368_PEA_1_T11 (SEQ 3090 3123 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 2937 2970 NO: 59) Z21368_PEA_1_T6 (SEQ ID 2937 2970 NO: 60) Z21368_PEA_1_T9 (SEQ ID 2867 2900 NO: 61)

[0981] Segment cluster Z21368_PEA.sub.--1_node.sub.--68 (SEQ ID NO 94) according to the present invention is supported by 87 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 39 below describes the starting and ending position of this segment on each transcript. TABLE-US-00227 TABLE 39 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 4375 4427 ID NO: 55) Z21368_PEA_1_T11 (SEQ 4297 4349 ID NO: 56) Z21368_PEA_1_T5 (SEQ ID 4144 4196 NO: 59) Z21368_PEA_1_T6 (SEQ ID 4144 4196 NO: 60) Z21368_PEA_1_T9 (SEQ ID 4074 4126 NO: 61)

[0982] Segment cluster Z21368_PEA.sub.--1_node.sub.--7 (SEQ ID NO:95) according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:55), Z21368_PEA.sub.--1_T11 (SEQ ID NO:56), Z21368_PEA.sub.--1_T23 (SEQ ID NO:57), Z21368_PEA.sub.--1_T24 (SEQ ID NO:58), Z21368_PEA.sub.--1_T5 (SEQ ID NO:59), Z21368_PEA.sub.--1_T6 (SEQ ID NO:60) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:61). Table 40 below describes the starting and ending position of this segment on each transcript. TABLE-US-00228 TABLE 40 Segment location on transcripts Segment Segment Transcript name starting position ending position Z21368_PEA_1_T10 (SEQ 463 557 ID NO: 55) Z21368_PEA_1_T11 (SEQ 463 557 ID NO: 56) Z21368_PEA_1_T23 (SEQ 463 557 ID NO: 57) Z21368_PEA_1_T24 (SEQ 463 557 ID NO: 58) Z21368_PEA_1_T5 (SEQ ID 301 395 NO: 59) Z21368_PEA_1_T6 (SEQ ID 301 395 NO: 60) Z21368_PEA_1_T9 (SEQ ID 328 422 NO: 61)

[0983] Overexpression of at least a portion of this cluster was determined according to oligonucleotides and one or more chips. The results were as follows: Oligonucleotide Z21368.sub.--0.sub.--0.sub.--61857 was on the TAA chip and was found to be overexpressed in breast cancer.

[0984] Variant protein alignment to the previously known protein:

[0985] Sequence name: /tmp/5ER3vIMKE2/9L0Y7lDlTQ:SUL1_HUMAN (SEQ ID NO:96)

[0986] Sequence documentation:

[0987] Alignment of: Z21368_PEA.sub.--1_P2 (SEQ ID NO:97).times.SUL1_HUMAN (SEQ ID NO:96).

[0988] Alignment segment 1/1: TABLE-US-00229 Quality: 7664.00 Score: 0 Matching length: 761 Total length: 761 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[0989] Alignment: TABLE-US-00230 . . . . . 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 . . . . . 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 . . . . . 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 . . . . . 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 . . . . . 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 . . . . . 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 . . . . . 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 |||||||||||||||||||||||||||||||||||||||||||||||||| 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 . . . . . 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 |||||||||||||||||||||||||||||||||||||||||||||||||| 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 . . . . . 401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450 |||||||||||||||||||||||||||||||||||||||||||||||||| 401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450 . . . . . 451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500 |||||||||||||||||||||||||||||||||||||||||||||||||| 451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500 . . . . . 501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550 |||||||||||||||||||||||||||||||||||||||||||||||||| 501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550 . . . . . 551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600 |||||||||||||||||||||||||||||||||||||||||||||||||| 551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600 . . . . . 601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650 |||||||||||||||||||||||||||||||||||||||||||||||||| 601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650 . . . . . 651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700 |||||||||||||||||||||||||||||||||||||||||||||||||| 651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700 . . . . . 701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750 |||||||||||||||||||||||||||||||||||||||||||||||||| 701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750 . 751 NNHWQTAPFWN 761 ||||||||||| 751 NNHWQTAPFWN 761

[0990] Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:Q7Z2W2 (SEQ ID NO:840)

[0991] Sequence documentation:

[0992] Alignment of: Z21368_PEA.sub.--1_P5 (SEQ ID NO:98).times.Q7Z2W2 (SEQ ID NO:840).

[0993] Alignment segment 1/1: TABLE-US-00231 Quality: 7869.00 Score: 0 Matching length: 791 Total length: 871 Matching Percent 99.87 Matching Percent Identity: 99.87 Similarity: Total Percent Similarity: 90.70 Total Percent Identity: 90.70 Gaps: 1

[0994] Alignment: TABLE-US-00232 . . . . . 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 . . . . . 51 DDQDVELA.......................................... 58 ||||||| 51 DDQDVELGSLQVMNKTRKIMEHGGATFTNAFVTTPMCCPSRSSMLTGKYV 100 . . . . . 59 ......................................FFGKYLNEYNGS 70 |||||||||||| 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTVFFGKYLNEYNGS 150 . . . . . 71 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 120 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 . . . . . 121 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 170 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 NYFKMSKRMYPHRPVMMVISHAAPRGPEDSAPQFSKLYPNASQHITPSYN 250 . . . . . 171 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 220 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 . . . . . 221 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 270 |||||||||||||||||||||||||||||||||||||||||||||||||| 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 . . . . . 271 PGSIVPQIVLNIDLAPTILDTAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 320 |||||||||||||||||||||||||||||||||||||||||||||||||| 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 . . . . . 321 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 370 |||||||||||||||||||||||||||||||||||||||||||||||||| 401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450 . . . . . 371 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 420 |||||||||||||||||||||||||||||||||||||||||||||||||| 451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500 . . . . . 421 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 470 |||||||||||||||||||||||||||||||||||||||||||||||||| 501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQRRSLSVEF 550 . . . . . 471 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 520 |||||||||||||||||||||||||||||||||||||||||||||||||| 551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600 . . . . . 521 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 570 |||||||||||||||||||||||||||||||||||||||||||||||||| 601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650 . . . . . 571 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 620 |||||||||||||||||||||||||||||||||||||||||||||||||| 651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700 . . . . . 621 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 670 |||||||||||||||||||||||||||||||||||||||||||||||||| 701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750 . . . . . 671 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 720 |||||||||||||||||||||||||||||||||||||||||||||||||| 751 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 800 . . . . . 721 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 770 |||||||||||||||||||||||||||||||||||||||||||||||||| 801 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 850 . . 771 GNKDGGSYDLHRGQLWDGWEG 791 ||||||||||||||||||||| 851 GNKDGGSYDLHRGQLWDGWEG 871

[0995] Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:AAH12997 (SEQ ID NO:841)

[0996] Sequence documentation:

[0997] Alignment of: Z21368_PEA.sub.--1_P5 (SEQ ID NO:98).times.AAH12997 (SEQ ID NO:841).

[0998] Alignment segment 1/1: TABLE-US-00233 Quality: 420.00 Score: 0 Matching length: 40 Total length: 40 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[0999] Alignment: TABLE-US-00234 . . . . 752 LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG 791 |||||||||||||||||||||||||||||||||||||||| 1 LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG 40

[1000] Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:SUL1_HUMAN (SEQ ID NO:96)

[1001] Sequence documentation:

[1002] Alignment of: Z21368_PEA.sub.--1_P5 (SEQ ID NO:98).times.SUL1_HUMAN (SEQ ID NO:96).

[1003] Alignment segment 1/1: TABLE-US-00235 Quality: 7878.00 Score: 0 Matching length: 791 Total length: 871 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 90.82 Total Percent Identity: 90.82 Gaps: 1

[1004] Alignment: TABLE-US-00236 . . . . . 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 . . . . . 51 DDQDVEL........................................... 57 ||||||| 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 . . . . . 58 .....................................AFFGKYLNEYNGS 70 ||||||||||||| 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 . . . . . 71 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 120 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 . . . . . 121 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 170 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 . . . . . 171 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 220 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 . . . . . 221 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 270 |||||||||||||||||||||||||||||||||||||||||||||||||| 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 . . . . . 271 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 320 |||||||||||||||||||||||||||||||||||||||||||||||||| 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 . . . . . 321 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 370 |||||||||||||||||||||||||||||||||||||||||||||||||| 401 NKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARY 450 . . . . . 371 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 420 |||||||||||||||||||||||||||||||||||||||||||||||||| 451 QTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDK 500 . . . . . 421 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 470 |||||||||||||||||||||||||||||||||||||||||||||||||| 501 DKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEF 550 . . . . . 471 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 520 |||||||||||||||||||||||||||||||||||||||||||||||||| 551 EGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLA 600 . . . . . 521 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 570 |||||||||||||||||||||||||||||||||||||||||||||||||| 601 DSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEI 650 . . . . . 571 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 620 |||||||||||||||||||||||||||||||||||||||||||||||||| 651 EALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLH 700 . . . . . 621 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 670 |||||||||||||||||||||||||||||||||||||||||||||||||| 701 PFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHD 750 . . . . . 671 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 720 |||||||||||||||||||||||||||||||||||||||||||||||||| 751 NNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEY 800 . . . . . 721 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 770 |||||||||||||||||||||||||||||||||||||||||||||||||| 801 FDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDV 850 . . 771 GNKDGGSYDLHRGQLWDGWEG 791 ||||||||||||||||||||| 851 GNKDGGSYDLHRGQLWDGWEG 871

[1005] Sequence name: /tmp/AVAZGWHuF0/RzHFOnHIsT:SUL1_HUMAN (SEQ ID NO:96)

[1006] Sequence documentation:

[1007] Alignment of: Z21368_PEA.sub.--1_P15 (SEQ ID NO:99).times.SUL1_HUMAN (SEQ ID NO:96).

[1008] Alignment segment 1/1: TABLE-US-00237 Quality: 4174.00 Escore: 0 Matching length: 416 Total length: 416 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[1009] Alignment: TABLE-US-00238 . . . . . 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 . . . . . 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 . . . . . 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 . . . . . 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 . . . . . 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 . . . . . 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 . . . . . 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 |||||||||||||||||||||||||||||||||||||||||||||||||| 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 . . . . . 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 |||||||||||||||||||||||||||||||||||||||||||||||||| 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRT 400 . 401 NKKAKIWRDTFLVERG 416 |||||||||||||||| 401 NKKAKIWRDTFLVERG 416

[1010] Sequence name: /tmp/JhwgRdKqmt/kqSmjxkWWk:SUL1_HUMAN (SEQ ID NO:96)

[1011] Sequence documentation:

[1012] Alignment of: Z21368_PEA.sub.--1_P16 (SEQ ID NO:100).times.SUL1_HUMAN (SEQ ID NO:96).

[1013] Alignment segment 1/1: TABLE-US-00239 Quality: 3985.00 Escore: 0 Matching length: 397 Total length: 397 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[1014] Alignment: TABLE-US-00240 . . . . . 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 . . . . . 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 . . . . . 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 . . . . . 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 |||||||||||||||||||||||||||||||||||||||||||||||||| 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESI 200 . . . . . 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 |||||||||||||||||||||||||||||||||||||||||||||||||| 201 NYFKMSKRMYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYN 250 . . . . . 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 |||||||||||||||||||||||||||||||||||||||||||||||||| 251 YAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNML 300 . . . . . 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 |||||||||||||||||||||||||||||||||||||||||||||||||| 301 VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVE 350 . . . . 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR 397 ||||||||||||||||||||||||||||||||||||||||||||||| 351 PGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR 397

[1015] Sequence name: /tmp/GPlnIw3BOg/zXFdxqG4ow:SUL1_HUMAN (SEQ ID NO:96)

[1016] Sequence documentation:

[1017] Alignment of: Z21368_PEA.sub.--1_P22 (SEQ ID NO:101).times.SUL1_HUMAN (SEQ ID NO:96).

[1018] Alignment segment 1/1: TABLE-US-00241 Quality: 1897.00 Escore: 0 Matching length: 188 Total length: 188 Matching Percent 100.00 Matching Percent Identity: 100.00 Similarity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[1019] Alignment: TABLE-US-00242 . . . . . 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 . . . . . 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 . . . . . 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 |||||||||||||||||||||||||||||||||||||||||||||||||| 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNEYNGS 150 . . . 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK 188 |||||||||||||||||||||||||||||||||||||| 151 YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK 188

[1020] Sequence name: /tmp/oji5Fs74fB/8xeB9KrGjp:Q7Z2W2 (SEQ ID NO:840)

[1021] Sequence documentation:

[1022] Alignment of: Z21368_PEA.sub.--1_P23 (SEQ ID NO:102).times.Q7Z2W2 (SEQ ID NO:840).

[1023] Alignment segment 1/1: TABLE-US-00243 Quality: 1368.00 Escore: 0.000511 Matching length: 137 Total length: 137 Matching Percent 100.00 Matching Percent 100.00 Similarity: Identity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[1024] Alignment: TABLE-US-00244 . . . . . 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 . . . . . 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 . . . 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137 ||||||||||||||||||||||||||||||||||||| 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137

[1025] Sequence name: /tmp/oji5Fs74fB/8xeB9KrGjp:SUL1_HUMAN (SEQ ID NO:96)

[1026] Sequence documentation:

[1027] Alignment of: Z21368_PEA.sub.--1_P23 (SEQ ID NO:102).times.SUL1_HUMAN (SEQ ID NO:96).

[1028] Alignment segment 1/1: TABLE-US-00245 Quality: 1368.00 Escore: 0.000511 Matching length: 137 Total length: 137 Matching Percent 100.00 Matching Percent 100.00 Similarity: Identity: Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0

[1029] Alignment: TABLE-US-00246 . . . . . 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 |||||||||||||||||||||||||||||||||||||||||||||||||| 1 MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLT 50 . . . . . 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 |||||||||||||||||||||||||||||||||||||||||||||||||| 51 DDQDVELGSLQVMNKTRKIMEHGGATFINAFVTTPMCCPSRSSMLTGKYV 100 . . . 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137 ||||||||||||||||||||||||||||||||||||| 101 HNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT 137

Expression of SUL1_HUMAN--Extracellular Sulfatase Sulf-1Z21368 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name Z21368seg39 (SEQ ID NO:844) in Normal and Cancerous Breast Tissues

[1030] Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts detectable by or according to seg39, Z21368seg39 (SEQ ID NO:844) amplicon and Z21368seg39F (SEQ ID NO:842) and Z21368seg39R (SEQ ID NO:843) primers was measured by real time PCR. In parallel the expression of four housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926), amplicon--PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID NO:930); amplicon--HPRT1-amplicon (SEQ ID NO:933)), SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:922); amplicon--SDHA-amplicon (SEQ ID NO:925)), and G6PD (GenBank Accession No. NM.sub.--000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 56-60,63-67, Table 1 above, Tissue samples in testing panel), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

[1031] FIG. 13 is a histogram showing over expression of the above-indicated SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. The number and percentage of samples that exhibit at least 5-fold over-expression, out of the total number of samples tested is indicated in the bottom.

[1032] As is evident from FIG. 13, the expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos 56-60,63-67, Table 1 above, Tissue samples in testing panel). Notably an over-expression of at least 5 fold was found in 13 out of 28 adenocarcinoma samples.

[1033] Statistical analysis was applied to verify the significance of these results, as described below.

[1034] The P value for the difference in the expression levels of SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 2.14E-03.

[1035] Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 6.91E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

[1036] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: Z21368seg39F forward primer (SEQ ID NO:842); Z21368seg39R reverse primer (SEQ ID NO:843).

[1037] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: Z21368seg39 (SEQ ID NO:844). TABLE-US-00247 Z21368seg39F (SEQ ID NO: 842)- GTTGCATTTCTCAGTGCTGGTTT Z21368seg39R (SEQ ID NO: 843)- AGGGTGCCGGGTGAGG Z21368seg39 (SEQ ID NO: 844)- GTTGCATTTCTCAGTGCTGGTTTCTAATCAGACCAGTGGATTGAGTTTCTCTACCATC CTCCCCACGTTCTTCTCTAAGCTGCCTCCAAGCCTCACCCGGCACCCT

Expression of SUL1_HUMAN--Extracellular Sulfatase Sulf-1Z21368 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name Z21368seg39 (SEQ ID NO:844) in Different Normal Tissues

[1038] Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts detectable by or according to Z21368seg39 (SEQ ID NO:844) amplicon and Z21368seg39F (SEQ ID NO:842) Z21368seg39R (SEQ ID NO:843) was measured by real time PCR. In parallel the expression of four housekeeping genes--[RPL19 (GenBank Accession No. NM.sub.--000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM.sub.--003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon--Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:922); amplicon--SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (sample nos. 33-35 in table 2 "Tissue samples in normal panel") to obtain a value of relative expression of each sample relative to median of the Normal samples. Primers and amplicon are as above.

[1039] The results are presented in FIG. 14, demonstrating the expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368seg39 (SEQ ID NO:844), in different normal tissues.

Expression of SUL1_HUMAN--Extracellular Sulfatase Sulf-1Z21368 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name Z21368junc17-21 (SEQ ID NO:847) in Normal and Cancerous Breast Tissues

[1040] Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts detectable by or according to Z21368junc17-21 (SEQ ID NO:847) amplicon and Z21368junc17-21F (SEQ ID NO:845) and Z21368junc17-21R (SEQ ID NO:846) primers was measured by real time PCR. In parallel the expression of four housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID NO:926); amplicon--PBGD-amplicon (SEQ ID NO:929)), HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID NO:930); amplicon--HPRT1-amplicon (SEQ ID NO:933)), and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:922); amplicon--SDHA-amplicon (SEQ ID NO:925)), G6PD (GenBank Accession No. NM.sub.--000402 (SEQ ID NO:918); G6PD-amplicon (SEQ ID NO:921)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos 56-60,63-67 Table 1 above, "Tissue samples in testing panel"), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples.

[1041] FIG. 15 is a histogram showing over expression of the above-indicated SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts in cancerous breast samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained. The number and percentage of samples that exhibit at least 5 fold over-expression, out of the total number of samples tested is indicated in the bottom.

[1042] As is evident from FIG. 15, the expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos 56-60,63-67, Table 1 above, Tissue samples in testing panel). Notably an over-expression of at least 5 fold was found in 11 out of 28 adenocarcinoma samples.

[1043] Statistical analysis was applied to verify the significance of these results, as described below.

[1044] The P value for the difference in the expression levels of SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts detectable by the above amplicon(s) in breast cancer samples versus the normal tissue samples was determined by T test as 4.6E-03.

[1045] Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.78E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: Z21368junc17-21F forward primer (SEQ ID NO:845); Z21368junc17-21R reverse primer (SEQ ID NO:846).

[1046] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: Z21368junc17-21 (SEQ ID NO:847) TABLE-US-00248 Z21368junc17-21F (SEQ ID NO: 845)- GGACGGATACAGCAGGAACG Z21368junc17-21R (SEQ ID NO: 846)- TATTTTCCAAAAAAGGCCAGCTC Z21368junc17-21 (SEQ ID NO: 847)- GGACGGATACAGCAGGAACGAAAAAACATCCGACCCAACATTATTCTTGTGCTTAC CGATGATCAAGATGTGGAGCTGGCCTTTTTTGGAAAATA

Expression of SUL1_HUMAN--Extracellular Sulfatase Sulf-1 Z21368 Transcripts Which are Detectable by Amplicon as Depicted in Sequence Name Z21368junc17-21 (SEQ ID NO:847) in Different Normal Tissues

[1047] Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1 Z21368 transcripts detectable by or according to amplicon Z21368junc17-21 (SEQ ID NO:847) was measured by real time PCR. In parallel the expression of four housekeeping genes--RPL19 (GenBank Accession No. NM.sub.--000981 (SEQ ID NO:934); RPL19 amplicon (SEQ ID NO:937)), TATA box (GenBank Accession No. NM.sub.--003194 (SEQ ID NO:938); TATA amplicon (SEQ ID NO:941)), UBC (GenBank Accession No. BC000449 (SEQ ID NO:942); amplicon--Ubiquitin-amplicon (SEQ ID NO:945)) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:922); amplicon--SDHA-amplicon (SEQ ID NO:925)) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes, as above. The normalized quantity of each RT sample was then divided by the median of the quantities of the breast samples (Sample Nos.--33-35 Table 2 above, "Tissue samples on normal panel"), to obtain a value of relative expression of each sample relative to median of the breast samples. Primers and amplicon are as above.

[1048] The results are presented in FIG. 16, demonstrating the expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1 Z21368 transcripts, which are detectable by amplicon as depicted in sequence name Z21368junc17-21 (SEQ ID NO:847), in different normal tissues.

Description for Cluster T59832

[1049] Cluster T59832 features 6 transcript(s) and 33 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the 5 application. The selected protein variants are given in table 3. TABLE-US-00249 TABLE 1 Transcripts of interest Transcript Name Sequence ID No T59832_T11 103 T59832_T15 104 T59832_T22 105 T59832_T28 106 T59832_T6 107 T59832_T8 108

[1050] TABLE-US-00250 TABLE 2 Segments of interest Segment Name Sequence ID No T59832_node_1 109 T59832_node_22 110 T59832_node_23 111 T59832_node_24 112 T59832_node_29 113 T59832_node_39 114 T59832_node_7 115 T59832_node_10 116 T59832_node_11 117 T59832_node_12 118 T59832_node_14 119 T59832_node_16 120 T59832_node_19 121 T59832_node_2 122 T59832_node_20 123 T59832_node_25 124 T59832_node_26 125 T59832_node_27 126 T59832_node_28 127 T59832_node_3 128 T59832_node_30 129 T59832_node_31 130 T59832_node_32 131 T59832_node_34 132 T59832_node_35 133 T59832_node_36 134 T59832_node_37 135 T59832_node_38 136 T59832_node_4 137 T59832_node_5 138 T59832_node_6 139 T59832_node_8 140 T59832_node_9 141

[1051] TABLE-US-00251 TABLE 3 Proteins of interest Protein Name Sequence ID No T59832_P5 143 T59832_P7 144 T59832_P9 145 T59832_P12 146 T59832_P18 147

[1052] These sequences are variants of the known protein Gamma-interferon inducible lysosomal thiol reductase precursor (SwissProt accession identifier GILT_HUMAN; known also according to the synonyms Gamma-interferon-inducible protein IP-30), SEQ ID NO: 142, referred to herein as the previously known protein.

[1053] Protein Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) is known or believed to have the following function(s): Cleaves disulfide bonds in proteins by reduction. May facilitate the complet unfolding of proteins destined for lysosomal degradation. May be involved in MHC class II-restricted antigen processing. The sequence for protein Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) is given at the end of the application, as "Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. TABLE-US-00252 TABLE 4 Amino acid mutations for Known Protein SNP position(s) on amino acid sequence Comment 109 L -> S 130 H -> L

[1054] Protein Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) localization is believed to be Lysosomal.

[1055] The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: extracellular; lysosome, which are annotation(s) related to Cellular Component.

[1056] The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

[1057] Cluster T59832 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of FIG. 17 refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

[1058] Overall, the following results were obtained as shown with regard to the histograms in FIG. 17 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, breast malignant tumors, ovarian carcinoma and pancreas carcinoma. TABLE-US-00253 TABLE 5 Normal tissue distribution Name of Tissue Number Adrenal 208 Bladder 205 Bone 200 Brain 18 Colon 236 Epithelial 143 General 280 head and neck 192 Kidney 71 Liver 53 Lung 459 lymph nodes 248 Breast 0 bone marrow 94 Ovary 0 Pancreas 20 Prostate 86 Skin 29 Stomach 109 T cells 557 Thyroid 0 Uterus 63

[1059] TABLE-US-00254 TABLE 6 P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 4.9e-01 5.9e-01 4.7e-03 1.1 2.9e-02 0.8 bladder 3.7e-01 5.6e-01 3.7e-02 1.3 2.5e-01 0.9 Bone 6.6e-01 6.7e-01 3.4e-01 0.6 9.1e-01 0.4 Brain 1.8e-01 2.9e-01 4.3e-03 3.8 2.8e-02 2.5 colon 4.4e-01 5.2e-01 6.1e-01 0.9 8.1e-01 0.7 epithelial 2.5e-02 1.6e-01 1.2e-05 1.6 9.8e-02 1.1 general 1.3e-02 1.6e-01 1 0.8 1 0.6 Head and neck 3.4e-01 3.3e-01 1 0.4 9.4e-01 0.5 kidney 7.7e-01 8.5e-01 1.4e-01 1.3 4.2e-01 0.9 Liver 8.3e-01 7.6e-01 1 0.5 1 0.6 Lung 5.7e-01 8.3e-01 3.5e-01 0.8 9.8e-01 0.5 lymph nodes 5.7e-01 6.6e-01 7.6e-01 0.8 3.6e-02 1.1 breast 5.0e-02 1.3e-01 2.5e-03 6.5 4.4e-02 3.6 Bone marrow 6.2e-01 7.8e-01 1 0.3 9.5e-01 0.5 ovary 2.2e-01 9.4e-02 3.2e-03 6.1 8.3e-03 5.3 pancreas 9.0e-02 1.6e-02 1.1e-03 4.0 7.9e-04 4.2 prostate 8.1e-01 8.0e-01 5.7e-01 0.9 4.1e-01 0.9 skin 1.6e-01 1.2e-01 2.3e-02 6.0 1.0e-02 2.2 stomach 5.5e-01 7.4e-01 9.4e-01 0.6 4.9e-01 1.0 T cells 1 6.7e-01 6.9e-01 1.0 9.8e-01 0.5 Thyroid 2.3e-01 2.3e-01 5.9e-02 2.5 5.9e-02 2.5 uterus 7.4e-02 4.7e-02 2.2e-02 2.0 6.2e-02 1.7

[1060] As noted above, cluster T59832 features 6 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142). A description of each variant protein according to the present invention is now provided.

[1061] Variant protein T59832_P5 (SEQ ID NO:143) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T6 (SEQ ID NO:107). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application.

[1062] Comparison report between T59832_P5 (SEQ ID NO:143) and GILT_HUMAN (SEQ ID NO:142):

[1063] 1. An isolated chimeric polypeptide encoding for T59832_P5 (SEQ ID NO:143), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 12-55 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-44 of T59832_P5 (SEQ ID NO:143), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG (SEQ ID NO:1010) corresponding to amino acids 45-189 of T59832_P5 (SEQ ID NO:143), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1064] 2. An isolated polypeptide encoding for a tail of T59832_P5 (SEQ ID NO:143), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00255 VGTATGRAGWREQAPCRGTRLLLSPQTSQGKTRAPRGRCPCRVPGKTLFSSRRCGHTP (SEQ ID NO: 1010) SVPFRFRIPHLRGAAASTRLVPPKGSMSAYCVLLGQELGSPFVAQGTSSAAGQGPPACIL AATLDAFIPARAGLACLWDLLGRCPRG in T59832_P5. (SEQ ID NO: 143)

[1065] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[1066] Variant protein T59832_P5 (SEQ ID NO:143) is encoded by the following transcript(s): T59832_T6 (SEQ ID NO:107), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T6 (SEQ ID NO:107) is shown in bold; this coding portion starts at position 149 and ends at position 715. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P5 (SEQ ID NO:143) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00256 TABLE 7 Nucleic acid SNPs SNP position on Alternative Previously nucleotide sequence nucleic acid known SNP? 61 C -> T Yes 148 G -> T Yes 1505 G -> C Yes 1651 T -> No 1652 T -> G Yes 1717 C -> A No 1722 C -> No 1722 C -> G No 1752 A -> G Yes 1817 A -> G Yes 1854 C -> No 1854 C -> A No 212 -> A No 1871 C -> T Yes 1886 T -> G No 1906 G -> A No 1906 G -> C No 1942 C -> No 1942 C -> T No 1971 C -> No 1986 G -> A No 2001 G -> T Yes 2008 A -> No 241 G -> T No 2030 -> T No 2031 C -> T No 2050 C -> No 2056 A -> G Yes 2068 G -> A Yes 2111 A -> C Yes 2136 A -> C Yes 2144 T -> C Yes 244 A -> G Yes 962 C -> T Yes 1074 G -> A Yes 1248 G -> C Yes 1441 G -> A Yes 1443 G -> A No

[1067] Variant protein T59832_P7 (SEQ ID NO:144) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T8 (SEQ ID NO:108). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142) ) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[1068] Comparison report between T59832_P7 (SEQ ID NO:144) and GILT_HUMAN (SEQ ID NO:142):

[1069] 1. An isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 12-223 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1070] 2. An isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

[1071] Comparison report between T59832_P7 (SEQ ID NO:144) and BAC98466 (SEQ ID NO:848):

[1072] 1. An isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1-212 of BAC98466 (SEQ ID NO:848), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1073] 2. An isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

[1074] Comparison report between T59832_P7 (SEQ ID NO:144) and BAC85622 (SEQ ID NO:849):

[1075] 1. An isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYV PWVTVNGVRIFLALSLTLIVPWSQGWTRQRDQR corresponding to amino acids 1-148 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1076] 2. An isolated polypeptide encoding for a head of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00257 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012) PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P7. (SEQ ID NO: 144)

[1077] Comparison report between T59832_P7 (SEQ ID NO:144) and Q8WU77 (SEQ ID NO:850):

[1078] 1. An isolated chimeric polypeptide encoding for T59832_P7 (SEQ ID NO:144), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 1-212 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-212 of T59832_P7 (SEQ ID NO:144), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) corresponding to amino acids 213-238 of T59832_P7 (SEQ ID NO:144), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1079] 2. An isolated polypeptide encoding for a tail of T59832_P7 (SEQ ID NO:144), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRIFLALSLTLIVPWSQGWTRQRDQR (SEQ ID NO:1011) in T59832_P7 (SEQ ID NO:144).

[1080] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide.

[1081] Variant protein T59832_P7 (SEQ ID NO:144) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P7 (SEQ ID NO:144) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00258 TABLE 8 Amino acid mutations SNP position(s) on Alternative Previously amino acid sequence amino acid(s) known SNP? 146 I -> No 146 I -> M Yes 168 P -> Q No 170 L -> No 170 L -> V No 180 M -> V Yes 76 R -> Q Yes 77 A -> T No

[1082] Variant protein T59832_P7 (SEQ ID NO:144) is encoded by the following transcript(s): T59832_T8 (SEQ ID NO:108), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T8 (SEQ ID NO:108) is shown in bold; this coding portion starts at position 149 and ends at position 862. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P7 (SEQ ID NO:144) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00259 TABLE 9 Nucleic acid SNPs SNP position on Alternative Previously nucleotide sequence nucleic acid known SNP? 61 C -> T Yes 148 G -> T Yes 651 C -> A No 656 C -> No 656 C -> G No 686 A -> G Yes 751 A -> G Yes 1004 T -> G Yes 1206 C -> No 1206 C -> A No 1223 C -> T Yes 1238 T -> G No 212 -> A No 1258 G -> A No 1258 G -> C No 1294 C -> No 1294 C -> T No 1323 C -> No 1338 G -> A No 1353 G -> T Yes 1360 A -> No 1382 -> T No 1383 C -> T No 241 G -> T No 1402 C -> No 1408 A -> G Yes 1420 G -> A Yes 1463 A -> C Yes 1488 A -> C Yes 1496 T -> C Yes 244 A -> G Yes 375 G -> A Yes 377 G -> A No 439 G -> C Yes 585 T -> No 586 T -> G Yes

[1083] Variant protein T59832_P9 (SEQ ID NO:145) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T11 (SEQ ID NO:103). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[1084] Comparison report between T59832_P9 (SEQ ID NO:145) and GILT_HUMAN (SEQ ID NO:2):

[1085] 1. An isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 12-214 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1086] 2. An isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

[1087] Comparison report between-T59832_P9 (SEQ ID NO:145) and BAC98466 (SEQ ID NO:848):

[1088] 1. An isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-203 of BAC98466 (SEQ ID NO:848), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1089] 2. An isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

[1090] Comparison report between T59832_P9 (SEQ ID NO:145) and BAC85622 (SEQ ID NO:849):

[1091] 1. An isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P9 (SEQ ID NO:145), second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVEACVLDELDMELAFLTIVC MEEFEDMERSLPLCLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-113 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-203 of T59832_P9 (SEQ ID NO:145), and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first, second and third amino acid sequences are contiguous and in a sequential order.

[1092] 2. An isolated polypeptide encoding for a head of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00260 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012) PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P9. (SEQ ID NO: 145)

[1093] 3. An isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

[1094] Comparison report between T59832_P9 (SEQ ID NO:145) and Q8WU77 (SEQ ID NO:850):

[1095] 1. An isolated chimeric polypeptide encoding for T59832_P9 (SEQ ID NO:145), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVEACVLDELDMELAFLTIVCMEEFEDMERSLPLCLQLYAPGLSPDTIM ECAMGDRGMQLMHANAQRTDALQPPHE corresponding to amino acids 1-203 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-203 of T59832_P9 (SEQ ID NO:145), and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TABLE-US-00261 (SEQ ID NO: 1013) NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR

corresponding to amino acids 204-244 of T59832_P9 (SEQ ID NO:145), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1096] 2. An isolated polypeptide encoding for a tail of T59832_P9 (SEQ ID NO:145), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NPWKIRPSSLPLSASCTRARSRMSALPQPAPSGVFASSDGR (SEQ ID NO:1013) in T59832_P9 (SEQ ID NO:145).

[1097] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[1098] Variant protein T59832_P9 (SEQ ID NO:145) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P9 SEQ ID NO:145) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00262 TABLE 10 Amino acid mutations SNP position(s) on Alternative Previously amino acid sequence amino acid(s) known SNP? 146 I -> No 146 I -> M Yes 222 A -> P No 222 A -> T No 234 P -> No 234 P -> S No 243 G -> No 76 R -> Q Yes 77 A -> T No 168 P -> Q No 170 L -> No 170 L -> V No 180 M -> V Yes 204 N -> No 204 N -> K No 210 P -> L Yes 215 L -> W No

[1099] Variant protein T59832_P9 (SEQ ID NO:145) is encoded by the following transcript(s): T59832_T11 (SEQ ID NO:103), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T11 (SEQ ID NO:103) is shown in bold; this coding portion starts at position 149 and ends at position 880. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P9 (SEQ ID NO:145) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00263 TABLE 11 Nucleic acid SNPs SNP position on Alternative Previously nucleotide sequence nucleic acid known SNP? 61 C -> T Yes 148 G -> T Yes 651 C -> A No 656 C -> No 656 C -> G No 686 A -> G Yes 751 A -> G Yes 760 C -> No 760 C -> A No 777 C -> T Yes 792 T -> G No 812 G -> A No 212 -> A No 812 G -> C No 848 C -> No 848 C -> T No 877 C -> No 892 G -> A No 907 G -> T Yes 914 A -> No 936 -> T No 937 C -> T No 956 C -> No 241 G -> T No 962 A -> G Yes 974 G -> A Yes 1017 A -> C Yes 1042 A -> C Yes 1050 T -> C Yes 244 A -> G Yes 375 G -> A Yes 377 G -> A No 439 G -> C Yes 585 T -> No 586 T -> G Yes

[1100] Variant protein T59832_P12 (SEQ ID NO:146) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T15 (SEQ ID NO:104). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[1101] Comparison report between T59832_P12 (SEQ ID NO:146) and GILT_HUMAN (SEQ ID NO:142):

[1102] 1. An isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 12-141 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-130 of T59832_P12 (SEQ ID NO:146), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173-261 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 131-219 of T59832_P12 (SEQ ID NO:146), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1103] 2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n-2)-x), in which x varies from 0 to n-2.

[1104] Comparison report between T59832_P12 (SEQ ID NO:146) and BAC85622 (SEQ ID NO:849):

[1105] 1. An isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLV (SEQ ID NO:1012) corresponding to amino acids 1-90 of T59832_P12 (SEQ ID NO:146), second amino acid sequence being at least 90% homologous to MEILNVTLVPYGNAQEQNVSGRWEFKCQHGEEECKFNKVE corresponding to amino acids 1-40 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 91-130 of T59832_P12 (SEQ ID NO:146), third amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNG corresponding to amino acids 72-122 of BAC85622 (SEQ ID NO:849), which also corresponds to amino acids 131-181 of T59832_P12 (SEQ ID NO:146), and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK (SEQ ID NO:1016) corresponding to amino acids 182-219 of T59832_P12 (SEQ ID NO:146), wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order.

[1106] 2. An isolated polypeptide encoding for a head of T59832_P12 (SEQ ID NO:146), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TABLE-US-00264 MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA (SEQ ID NO: 1012) PLVNVTLYYEALCGGCRAFLIRELFPTWLLV of T59832_P12. (SEQ ID NO: 146)

[1107] 3. An isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n-2)-x), in which x varies from 0 to n-2.

[1108] 4. An isolated polypeptide encoding for a tail of T59832_P12 (SEQ ID NO:146), comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KPLEDQTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK (SEQ ID NO:1016) in T59832_P12 (SEQ ID NO:146).

[1109] Comparison report between T59832_P12 (SEQ ID NO:146) and Q8WU77 (SEQ ID NO:850):

[1110] 1. An isolated chimeric polypeptide encoding for T59832_P12 (SEQ ID NO:146), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYKTGNLYLRGPLKKSNA PLVNVTLYYEALCGGCRAFLIRELFPTWLLVMEILNVTLVPYGNAQEQNVSGRWEFKC QHGEEECKFNKVE corresponding to amino acids 1-130 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-130 of T59832_P12 (SEQ ID NO:146), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 131-219 of T59832_P12 (SEQ ID NO:146), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1111] 2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P12 (SEQ ID NO:146), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EC, having a structure as follows: a sequence starting from any of amino acid numbers 130-x to 130; and ending at any of amino acid numbers 131+((n-2)-x), in which x varies from 0 to n-2.

[1112] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[1113] Variant protein T59832_P12 (SEQ ID NO:146) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P12 (SEQ ID NO:146) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00265 TABLE 12 Amino acid mutations SNP position(s) on Alternative Previously amino acid sequence amino acid(s) known SNP? 137 P -> Q No 139 L -> No 76 R -> Q Yes 77 A -> T No 139 L -> V No 149 M -> V Yes 183 P -> No 183 P -> T No 200 G -> A No 200 G -> D No 212 S -> No 212 S -> F No

[1114] Variant protein T59832_P12 (SEQ ID NO:146) is encoded by the following transcript(s): T59832_T15 (SEQ ID NO:104), for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T59832_T15 (SEQ ID NO:104) is shown in bold; this coding portion starts at position 149 and ends at position 805. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P12 (SEQ ID NO:146) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00266 TABLE 13 Nucleic acid SNPs SNP position on Alternative Previously nucleotide sequence nucleic acid known SNP? 61 C -> T Yes 148 G -> T Yes 563 C -> G No 593 A -> G Yes 658 A -> G Yes 695 C -> No 695 C -> A No 712 C -> T Yes 727 T -> G No 747 G -> A No 747 G -> C No 783 C -> No 212 -> A No 783 C -> T No 812 C -> No 827 G -> A No 842 G -> T Yes 849 A -> No 871 -> T No 872 C -> T No 891 C -> No 897 A -> G Yes 909 G -> A Yes 241 G -> T No 952 A -> C Yes 977 A -> C Yes 985 T -> C Yes 244 A -> G Yes 375 G -> A Yes 377 G -> A No 439 G -> C Yes 558 C -> A No 563 C -> No

[1115] Variant protein T59832_P18 (SEQ ID NO:147) according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) T59832_T22 (SEQ ID NO:105). An alignment is given to the known protein (Gamma-interferon inducible lysosomal thiol reductase precursor (SEQ ID NO:142)) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows:

[1116] Comparison report between T59832_P18 (SEQ ID NO:147) and GILT_HUMAN (SEQ ID NO:142):

[1117] 1. An isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 12-55 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 173-261 of GILT_HUMAN (SEQ ID NO:142), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1118] 2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n-2)-x), in which x varies from 0 to n-2.

[1119] Comparison report between T59832_P18 (SEQ ID NO:147) and Q8WU77 (SEQ ID NO:850):

[1120] 1. An isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1-44 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8WU77 (SEQ ID NO:850), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1121] 2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n-2)-x), in which x varies from 0 to n-2.

[1122] Comparison report between T59832_P18 (SEQ ID NO:147) and Q8NE14 (SEQ ID NO:851):

[1123] 1. An isolated chimeric polypeptide encoding for T59832_P18 (SEQ ID NO:147), comprising a first amino acid sequence being at least 90% homologous to MTLSPLLLFLPPLLLLLDVPTAAVQASPLQALDFFGNGPPVNYK corresponding to amino acids 1-44 of Q8NE14 (SEQ ID NO:851), which also corresponds to amino acids 1-44 of T59832_P18 (SEQ ID NO:147), and a second amino acid sequence being at least 90% homologous to CLQLYAPGLSPDTIMECAMGDRGMQLMHANAQRTDALQPPHEYVPWVTVNGKPLED QTQLLTLVCQLYQGKKPDVCPSSTSSLRSVCFK corresponding to amino acids 162-250 of Q8NE14 (SEQ ID NO:851), which also corresponds to amino acids 45-133 of T59832_P18 (SEQ ID NO:147), wherein said first and second amino acid sequences are contiguous and in a sequential order.

[1124] 2. An isolated chimeric polypeptide encoding for an edge portion of T59832_P18 (SEQ ID NO:147), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise KC, having a structure as follows: a sequence starting from any of amino acid numbers 44-x to 44; and ending at any of amino acid numbers 45+((n-2)-x), in which x varies from 0 to n-2.

[1125] The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

[1126] Variant protein T59832_P18 (SEQ ID NO:147) also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T59832_P18 (SEQ ID NO:147) sequence provides support for the deduced sequence of this variant protein according to the present invention). TABLE-US-00267 TABLE 14 Amino acid mutations SNP position(s) on Alternative Previously amino acid sequence amino acid(s) known SNP? 114 G -> A No 114 G -> D No 126 S -> No 126 S -> F No 51 P -> Q No 53 L -> No 53 L -> V No 63 M -> V Yes 97 P -> No 97 P -> T No

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