Detecting conserved secondary structures in RNA molecules using constrained structural alignment

Mugdha Khaladkar, Vandanaben Patel, Vivian Bellofatto, Jeffrey Wilusz, Jason T.L. Wang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Constrained sequence alignment has been studied extensively in the past. Different forms of constraints have been investigated, where a constraint can be a subsequence, a regular expression, or a probability matrix of symbols and positions. However, constrained structural alignment has been investigated to a much lesser extent. In this paper, we present an efficient method for constrained structural alignment and apply the method to detecting conserved secondary structures, or structural motifs, in a set of RNA molecules. The proposed method combines both sequence and structural information of RNAs to find an optimal local alignment between two RNA secondary structures, one of which is a query and the other is a subject structure in the given set. The method allows a biologist to annotate conserved regions, or constraints, in the query RNA structure and incorporates these regions into the alignment process to obtain biologically more meaningful alignment scores. A statistical measure is developed to assess the significance of the scores. Experimental results based on detecting internal ribosome entry sites in the RNA molecules of hepatitis C virus and Trypanosoma brucei demonstrate the effectiveness of the proposed method and its superiority over existing techniques.

Original languageEnglish (US)
Pages (from-to)264-272
Number of pages9
JournalComputational Biology and Chemistry
Volume32
Issue number4
DOIs
StatePublished - Aug 2008

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Organic Chemistry
  • Computational Mathematics

Keywords

  • Constrained structural alignment
  • RNA motif
  • Viruses and protozoa

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