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Genome Res. 14:1617-1623, 2004
©2004 by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/04 $5.00
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Methods

A Non-EST-Based Method for Exon-Skipping Prediction

Rotem Sorek1,2,4, Ronen Shemesh2, Yuval Cohen2, Ortal Basechess2, Gil Ast1 and Ron Shamir3

1 Department of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel 2 Compugen, Tel Aviv 69512, Israel 3 School of Computer Science, Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel

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.

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.2572604.

4 Corresponding author.
E-MAIL rotem{at}compugen.co.il; FAX 972 3-7658555.

[Supplemental material is available online at www.genome.org.]


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