Home LiteratureArticle Details
PMID: 15289480 Published · ppublish English Comparative Study Journal Article Validation Study

A non-EST-based method for exon-skipping prediction.

Genome research ·Vol. 14 ·No. 8 ·2004-08-00 ·Pages 1617-23

Sorek R, Shemesh R, Cohen Y, Basechess O, Ast G, Shamir R

Abstract

It is estimated that between 35% and 74% of all human genes can undergo alternative splicing. Currently, the most efficient methods for large-scale detection of alternative splicing use expressed sequence tags (ESTs) or microarray analysis. As these methods merely sample the transcriptome, splice variants that do not appear in deeply sampled tissues have a low probability of being detected. We present a new method by which we can predict that an internal exon is skipped (namely whether it is a cassette-exon) merely based on its naked genomic sequence and on the sequence of its mouse ortholog. No other data, such as ESTs, are required for the prediction. Using our method, which was experimentally validated, we detected hundreds of novel splice variants that were not detectable using ESTs. We show that a substantial fraction of the splice variants in the human genome could not be identified through current human EST or cDNA data.

MeSH Terms
Alternative Splicing Animals Computational Biology/methods Databases, Nucleic Acid Exons Expressed Sequence Tags Genome, Human Humans Introns Mice Models, Genetic RNA, Messenger/genetics
Chemicals
RNA, Messenger
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sorek Rotem
Department of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel. rotem@compugen.co.il
Shemesh Ronen
Cohen Yuval
Basechess Ortal
Ast Gil
Shamir Ron
References (25)
25 references, click to expand
  1. GCG: The Wisconsin Package of sequence analysis programs.
    Methods Mol Biol. 2000;132:3-22 PMID: 10547828
  2. A computer program for aligning a cDNA sequence with a genomic DNA sequence.
    Genome Res. 1998 Sep;8(9):967-74 PMID: 9750195
  3. EST comparison indicates 38% of human mRNAs contain possible alternative splice forms.
    FEBS Lett. 2000 May 26;474(1):83-6 PMID: 10828456
  4. Alternative splicing: increasing diversity in the proteomic world.
    Trends Genet. 2001 Feb;17(2):100-7 PMID: 11173120
  5. Initial sequencing and analysis of the human genome.
    Nature. 2001 Feb 15;409(6822):860-921 PMID: 11237011
  6. Gene structure prediction and alternative splicing analysis using genomically aligned ESTs.
    Genome Res. 2001 May;11(5):889-900 PMID: 11337482
  7. Genome-wide detection of alternative splicing in expressed sequences of human genes.
    Nucleic Acids Res. 2001 Jul 1;29(13):2850-9 PMID: 11433032
  8. A genomic view of alternative splicing.
    Nat Genet. 2002 Jan;30(1):13-9 PMID: 11753382
  9. Listening to silence and understanding nonsense: exonic mutations that affect splicing.
    Nat Rev Genet. 2002 Apr;3(4):285-98 PMID: 11967553
  10. Alu-containing exons are alternatively spliced.
    Genome Res. 2002 Jul;12(7):1060-7 PMID: 12097342
  11. Alternative pre-mRNA splicing and proteome expansion in metazoans.
    Nature. 2002 Jul 11;418(6894):236-43 PMID: 12110900
  12. Selecting for functional alternative splices in ESTs.
    Genome Res. 2002 Dec;12(12):1837-45 PMID: 12466287
  13. Prediction and statistical analysis of alternatively spliced exons.
    Prog Mol Subcell Biol. 2003;31:1-31 PMID: 12494761
  14. Ensembl 2002: accommodating comparative genomics.
    Nucleic Acids Res. 2003 Jan 1;31(1):38-42 PMID: 12519943
  15. A novel algorithm for computational identification of contaminated EST libraries.
    Nucleic Acids Res. 2003 Feb 1;31(3):1067-74 PMID: 12560505
  16. Low conservation of alternative splicing patterns in the human and mouse genomes.
    Hum Mol Genet. 2003 Jun 1;12(11):1313-20 PMID: 12761046
  17. Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss.
    Nat Genet. 2003 Jun;34(2):177-80 PMID: 12730695
  18. Intronic sequences flanking alternatively spliced exons are conserved between human and mouse.
    Genome Res. 2003 Jul;13(7):1631-7 PMID: 12840041
  19. Improving the Arabidopsis genome annotation using maximal transcript alignment assemblies.
    Nucleic Acids Res. 2003 Oct 1;31(19):5654-66 PMID: 14500829
  20. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays.
    Science. 2003 Dec 19;302(5653):2141-4 PMID: 14684825
  21. How prevalent is functional alternative splicing in the human genome?
    Trends Genet. 2004 Feb;20(2):68-71 PMID: 14746986
  22. Evidence for a subpopulation of conserved alternative splicing events under selection pressure for protein reading frame preservation.
    Nucleic Acids Res. 2004;32(4):1261-9 PMID: 14982953
  23. Exon recognition in vertebrate splicing.
    J Biol Chem. 1995 Feb 10;270(6):2411-4 PMID: 7852296
  24. Prediction of complete gene structures in human genomic DNA.
    J Mol Biol. 1997 Apr 25;268(1):78-94 PMID: 9149143
  25. Frequent alternative splicing of human genes.
    Genome Res. 1999 Dec;9(12):1288-93 PMID: 10613851
Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
Published
2004-08-00
Pages
1617-23
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC509271
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com