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

  • Authors:
  • Zasha Weinberg;Walter L. Ruzzo

  • Affiliations:
  • Department of Computer Science & Engineering Seattle, WA 98195, USA;Department of Computer Science & Engineering Seattle, WA 98195, USA

  • Venue:
  • Bioinformatics
  • Year:
  • 2006

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Abstract

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