Research Article: Detecting conserved secondary structures in RNA molecules using constrained structural alignment

  • Authors:
  • Mugdha Khaladkar;Vandanaben Patel;Vivian Bellofatto;Jeffrey Wilusz;Jason T. L. Wang

  • Affiliations:
  • Bioinformatics Program and Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102, USA;Bioinformatics Program and Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102, USA;Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, International Center for Public Health, 225 Warren Street, Newark, ...;Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA;Bioinformatics Program and Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102, USA and Department of Microbiology and Molecular Genetics, University of Medicine a ...

  • Venue:
  • Computational Biology and Chemistry
  • Year:
  • 2008

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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.