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Bioinformatics Advance Access originally published online on August 9, 2005
Bioinformatics 2005 21(19):3701-3703; doi:10.1093/bioinformatics/bti613
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions{at}oxfordjournals.org

Assessing the application of Ka/Ks ratio test to alternatively spliced exons

Yi Xing and Christopher Lee *

Department of Chemistry and Biochemistry, Molecular Biology Institute, Center for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA 90095-1570, USA

*To whom correspondence should be addressed.

Summary: Recently, the Ka/Ks ratio test, which assesses the protein-coding potentials of genomic regions based on their non-synonymous to synonymous divergence rates, has been proposed and successfully used in genome annotations of eukaryotes. We systematically performed the Ka/Ks ratio test on 925 transcript-confirmed alternatively spliced exons in the human genome, which we describe in this manuscript. We found that 22.3% of evolutionarily conserved alternatively spliced exons cannot pass the Ka/Ks ratio test, compared with 9.8% for constitutive exons. The false negative rate was the highest (85.7%) for exons with low frequencies of transcript inclusion. Analyses of alternatively spliced exons supported by full-length mRNA sequences yielded similar results, and nearly half of exons involved in ancestral alternative splicing events could not pass this test. Our analysis suggests a future direction to incorporate comparative genomics-based alternative splicing predictions with the Ka/Ks ratio test in higher eukaryotes with extensive RNA alternative splicing.

Contact: leec{at}mbi.ucla.edu

Received on July 5, 2005; revised on August 3, 2005; accepted on August 3, 2005

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