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    Comput Biol Chem. 2008 Aug;32(4):264-72. Epub 2008 Apr 8.

    Detecting conserved secondary structures in RNA molecules using constrained structural alignment.

    Khaladkar M, Patel V, Bellofatto V, Wilusz J, Wang JT.

    Bioinformatics Program and Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102, USA.

    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.

    PMID: 18472302 [PubMed - indexed for MEDLINE]

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