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Bioinformatics Advance Access originally published online on November 2, 2005
Bioinformatics 2006 22(1):35-39; doi:10.1093/bioinformatics/bti743
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Sequence-based heuristics for faster annotation of non-coding RNA families

Zasha Weinberg 1,* and Walter L. Ruzzo 1,2

1Department of Computer Science & Engineering Seattle, WA 98195, USA
2Department of Genome Sciences, University of Washington Seattle, WA 98195, USA

*To whom correspondence should be addressed.

Motivation: Non-coding RNAs (ncRNAs) are functional RNA molecules that do not code for proteins. Covariance Models (CMs) are a useful statistical tool to find new members of an ncRNA gene family in a large genome database, using both sequence and, importantly, RNA secondary structure information. Unfortunately, CM searches are extremely slow. Previously, we created rigorous filters, which provably sacrifice none of a CM's accuracy, while making searches significantly faster for virtually all ncRNA families. However, these rigorous filters make searches slower than heuristics could be.

Results: In this paper we introduce profile HMM-based heuristic filters. We show that their accuracy is usually superior to heuristics based on BLAST. Moreover, we compared our heuristics with those used in tRNAscan-SE, whose heuristics incorporate a significant amount of work specific to tRNAs, where our heuristics are generic to any ncRNA. Performance was roughly comparable, so we expect that our heuristics provide a high-quality solution that—unlike family-specific solutions—can scale to hundreds of ncRNA families.

Availability: The source code is available under GNU Public License at the supplementary web site.

Contact: zasha{at}cs.washington.edu

Supplementary information: http://bio.cs.washington.edu/supplements/zasha-HeurHmm-2004/ (Technical details, results, C++ code)

Received on December 13, 2004; revised on October 13, 2005; accepted on October 22, 2005

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