Predicting functional alternative splicing by measuring RNA selection pressure from multigenome alignments.

ABSTRACT: High-throughput methods such as EST sequencing, microarrays and deep sequencing have identified large numbers of alternative splicing (AS) events, but studies have shown that only a subset of these may be functional. Here we report a sensitive bioinformatics approach that identifies exons with evidence of a strong RNA selection pressure ratio (RSPR)--i.e., evolutionary selection against mutations that change only the mRNA sequence while leaving the protein sequence unchanged--measured across an entire evolutionary family, which greatly amplifies its predictive power. Using the UCSC 28 vertebrate genome alignment, this approach correctly predicted half to three-quarters of AS exons that are known binding targets of the NOVA splicing regulatory factor, and predicted 345 strongly selected alt

SUBMITTER: Lu H 

PROVIDER: S-EPMC2784930 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature