Bioinformatics Advance Access originally published online on February 26, 2004
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Bioinformatics 20(12) © Oxford University Press 2004; all rights reserved.
Multiple-sequence functional annotation and the generalized hidden Markov phylogeny
1 Department of Statistics, University of California, 367 Evans Hall, Berkeley, CA 94720, USA, 2 Department of Mathematics, University of California, 970 Evans Hall, Berkeley, CA 94720, USA and 3 Division of Computer Science, University of California, 387 Soda Hall, Berkeley, CA 94720, USA
Received on September 20, 2003; revised on January 4, 2004; accepted on January 20, 2004
Advance Access Publication February 26, 2004
Motivation: Phylogenetic shadowing is a comparative genomics principle that allows for the discovery of conserved regions in sequences from multiple closely related organisms. We develop a formal probabilistic framework for combining phylogenetic shadowing with feature-based functional annotation methods. The resulting model, a generalized hidden Markov phylogeny (GHMP), applies to a variety of situations where functional regions are to be inferred from evolutionary constraints.
Results: We show how GHMPs can be used to predict complete shared gene structures in multiple primate sequences. We also describe SHADOWER, our implementation of such a prediction system. We find that SHADOWER outperforms previously reported ab initio gene finders, including comparative human–mouse approaches, on a small sample of diverse exonic regions. Finally, we report on an empirical analysis of SHADOWER's performance which reveals that as few as five well-chosen species may suffice to attain maximal sensitivity and specificity in exon demarcation.
Availability: A Web server is available at http://bonaire.lbl.gov/shadower
Contact: jordan{at}cs.berkeley.edu
* To whom correspondence should be addressed.
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