Methods of identifying putative gene products by interspecies sequence comparison and biomolecular sequences uncovered thereby

• US 20070082337A1
• Filed: 01/27/2005
• Published: 04/12/2007
• Est. Priority Date: 01/27/2004
• Status: Abandoned Application

• Current Assignee: Compugen Ltd
• Original Assignee: Compugen Ltd
• Inventors: Cohen, Yossi, Levine, Zurit, Pollock, Sarah, Nemzer, Sergey, Haviv, Ami, Wool, Assaf, Kol, Guy, Savitsky, Kinneret, Cohen, Yuval, Sorek, Rotem, Diber, Alex, Shemesh, Ronen
• Application Number:
  US11/043,591
• Publication Number:
  US 20070082337A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 30/10 Sequence alignment; Homology search
• CPC Class Codes: G16B 30/20 Sequence assembly

Abstract

A method of identifying alternatively spliced exons is provided. The method comprising, scoring each of a plurality of exon sequences derived from genes of a species according to at least one sequence parameter, wherein exon sequences of the plurality of exon sequences scoring above a predetermined threshold represent alternatively spliced exons, thereby identifying the alternatively spliced exons.

Claims

1. A method of identifying alternatively spliced exons, the method comprising, scoring each of a plurality of exon sequences derived from genes of a species according to at least one sequence parameter, wherein exon sequences of said plurality of exon sequences scoring above a predetermined threshold represent alternatively spliced exons, thereby identifying the alternatively spliced exons.

2. The method of claim 1, wherein said at least one sequence parameter is selected from the group consisting of:

(i) exon length;

(ii) division by 3;

(iii) conservation level between said plurality of exon sequences of genes of a species and corresponding exon sequences of genes of an ortholohgous species;

(iv) length of conserved intron sequences upstream of each of said plurality of exon sequences;

(v) length of conserved intron sequences downstream of each of said plurality of exon sequences;

(vi) conservation level of said intron sequences upstream of each of said plurality of exon sequences; and

(vii) conservation level of said intron sequences downstream of each of said plurality of exon sequences;

3. The method of claim 2, wherein said exon length does not exceed 1000 bp.

4. The method of claim 2, wherein said conservation level is at least 95%.

5. The method of claim 2, wherein said length of conserved intron sequences upstream of each of said plurality of exon sequences is at least 12.

6. The method of claim 2, wherein said length of conserved intron sequences downstream of each of said plurality of exon sequences is at least 15.

7. The method of claim 2, wherein said conservation level of said intron sequences upstream of each of said plurality of exon sequences is at least 85%.

8. The method of claim 2, wherein said conservation level of said intron sequences downstream of each of said plurality of exon sequences is at least 60%.

9. A system for generating a database of alternatively spliced exons, the system comprising a processing unit, said processing unit executing a software application configured for:

(a) scoring each of a plurality of exon sequences derived from genes of a species according to at least one sequence parameter, wherein exon sequences of said plurality of exon sequences scoring above a predetermined threshold represent alternatively spliced exons, to thereby identify the alternatively spliced exons; and

(b) storing said identified alternatively spliced exons to thereby generate the database of alternatively spliced exons.

10. The system of claim 9, wherein said at least one sequence parameter is selected from the group consisting of:

(i) exon length;

(i) division by 3;

(iii) conservation level between said plurality of exon sequences of genes of a species and corresponding exon sequences of genes of an ortholohgous species;

(iv) length of conserved intron sequences upstream of each of said plurality of exon sequences;

(v) length of conserved intron sequences downstream of each of said plurality of exon sequences;

(vi) conservation level of said intron sequences upstream of each of said plurality of exon sequences; and

(vii) conservation level of said intron sequences downstream of each of said plurality of exon sequences;

11. The system of claim 10, wherein said exon length does not exceed 1000 bp.

12. The system of claim 10, wherein said conservation level is at least 95%.

13. The system of claim 10, wherein said length of conserved intron sequences upstream of each of said plurality of exon sequences is at least 12.

14. The system of claim 10, wherein said length of conserved intron sequences downstream of each of said plurality of exon sequences is at least 15.

15. The system of claim 10, wherein said conservation level of said intron sequences upstream of each of said plurality of exon sequences is at least 85%.

16. The system of claim 10, wherein said conservation level of said intron sequences downstream of each of said plurality of exon sequences is at least 60%.

17. A computer readable storage medium comprising data stored in a retrievable manner, said data including sequence information as set forth in the files “

transcripts. fasta” and

“

proteins.fasta”

of enclosed CD-ROM1 and the files forth in the file “

AnnotationForPatent.txt”

of enclosed CD-ROM1.

18. A method of predicting expression products of a gene of interest, the method comprising:

(a) scoring exon sequences of the gene of interest according to at least one sequence parameter and identifying exon sequences scoring above a predetermined threshold as alternatively spliced exons of the gene of interest; and

(b) analyzing chromosomal location of each of said alternatively spliced exons with respect to coding, sequence of the gene of interest to thereby predict expression products of the gene of interest.

19. The method of claim 18, wherein said at least one sequence parameter is selected from the group consisting of:

(i) exon length;

(ii) division by 3;

(iii) conservation level between said plurality of exon sequences of genes of a species and corresponding exon sequences of genes of an

(iv) orthologous species;

(iv) length of conserved intron sequences upstream of each of said plurality of exon sequences;

(v) length of conserved intron sequences downstream of each of said plurality of exon sequences;

(vi) conservation level of said intron sequences upstream of each of said plurality of exon sequences; and

(vii) conservation level of said intron sequences downstream of each of said plurality of exon sequences;

20. The method of claim 19, wherein said exon length does not exceed 1000 bp.

21. The method of claim 19, wherein said conservation level is at least 95%.

22. The method of claim 19, wherein said length of conserved intron sequences upstream of each of said plurality of exon sequences is at least 12.

23. The method of claim 19, wherein said length of conserved intron sequences downstream of each of said plurality of exon sequences is at least 15.

24. The method of claim 19, wherein said conservation level of said intron sequences upstream of each of said plurality of exon sequences is at least 85%.

25. The method of claim 19, wherein said conservation level of said intron sequences downstream of each of said plurality of exon sequences is at least 60%.

26. A method of predicting expression products of a gene of interest in a given species, the method comprising:

(a) providing a contig of exon sequences of the gene of interest of a first species;

(b) identifying exon sequences of an orthologue of the gene of interest of said first species which align to a genome of said first species;

(c) assembling said exon sequences of said orthologue of the gene of interest in said contig, thereby generating a hybrid contig;

(d) identifying in said hybrid contig, exon sequences of said orthologue of the gene of interest, which do not align with said exon sequences of the gene of interest of said first species, thereby uncovering non-overlapping exon sequences of the gene of interest; and

(e) analyzing chromosomal location of non-overlapping exon sequences of the gene of interest with respect to the chromosomal location of the gene of interest to thereby predict expression products of the gene of interest in a given species.

27. The method of claim 26, wherein at least a portion of said exon sequences are alternatively spliced sequences.

28. The method of claim 27, wherein said alternatively spliced sequences are identified by scoring exon sequences of the gene of interest according to at least one sequence parameter, wherein exon sequences scoring above a predetermined threshold represent said alternatively spliced exons of the gene of interest.

29. The method of claim 28, wherein said at least one sequence parameter is selected from the group consisting of:

(i) exon length;

(ii) division by 3;

(iii) conservation level between said plurality of exon sequences of genes of a species and corresponding exon sequences of genes of an orthologous species;

(iv) length of conserved intron sequences upstream of each of said plurality of exon sequences;

(v) length of conserved intron sequences downstream of each of said

plurality of exon sequences;

(vi) conservation level of said intron sequences upstream of each of said plurality of exon sequences; and

(vii) conservation level of said intron sequences downstream of each of said plurality of exon sequences;

30. The method of claim 29, wherein said exon length does not exceed 1000 bp.

31. The method of claim 29, wherein said conservation level is at least 95%.

32. The method of claim 29, wherein said length of conserved intron sequences upstream of each of said plurality of exon sequences is at least 12.

33. A The method of claim 29, wherein said length of conserved intron sequences downstream of each of said plurality of exon sequences is at least 15.

34. The method of claim 29, wherein said conservation level of said intron sequences upstream of each of said plurality of exon sequences is at least 85%.

35. The method of claim 29, wherein said conservation level of said intron sequences downstream of each of said plurality of exon sequences is at least 60%.

36. An isolated polynucleotide comprising a nucleic acid sequence being at least 70% identical to a nucleic acid sequence of the sequences set forth in file “

transcripts.fasta”

of CD-ROM1 or in the file “

transcripts”

of CD-ROM2.

37. The isolated polynucleotide of claim 36, wherein said nucleic acid sequence is set forth in the file “

transcripts.fasta”

of enclosed CD-ROM1 or in the file “

transcripts”

of enclosed CD-ROM 2.

38. An isolated polynucleotide comprising a nucleic acid sequence encoding a polypeptide having an amino acid sequence at least 70% homologous to a sequence set forth in the file “

proteins.fasta”

of enclosed CD-ROM or in the file “

proteins”

of enclosed CD-ROM2.

39. An isolated polypeptide having an amino acid sequence at least 80% homologous to a sequence set forth in the file proteins.fasta”

of enclosed CD-ROM1 or in the file “

proteins”

of enclosed CD-ROM2.

40. Use of a polynucleotide or polypeptide set forth in the file “

transcripts.fasta”

of CD-ROM1 or in the file “

transcripts”

of CD-ROM2 or in the file “

proteins.fasta”

of enclosed CD-ROM1 or in the file “

proteins”

of enclosed CD-ROM2 for the diagnosis and/or treatment of the diseases listed in Example 8.