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Nucleic Acids Research, 2002, Vol. 30, No. 23 5310-5317
© 2002 Oxford University Press

Discovery of RNA structural elements using evolutionary computation

Gary B. Fogel, V. William Porto, Dana G. Weekes, David B. Fogel, Richard H. Griffey1, John A. McNeil1, Elena Lesnik1, David J. Ecker1 and Rangarajan Sampath*,1

Natural Selection Inc., 3333 North Torrey Pines Court, Suite 200, La Jolla, CA 92037, USA and 1 Ibis Therapeutics, 1891 Rutherford Road, Carlsbad, CA 92008, USA

*To whom correspondence should be addressed. Tel: +1 760 603 2652; Fax: +1 760 603 4653; Email: rsampath{at}isisph.com

RNA molecules fold into characteristic secondary and tertiary structures that account for their diverse functional activities. Many of these RNA structures, or certain structural motifs within them, are thought to recur in multiple genes within a single organism or across the same gene in several organisms and provide a common regulatory mechanism. Search algorithms, such as RNAMotif, can be used to mine nucleotide sequence databases for these repeating motifs. RNAMotif allows users to capture essential features of known structures in detailed descriptors and can be used to identify, with high specificity, other similar motifs within the nucleotide database. However, when the descriptor constraints are relaxed to provide more flexibility, or when there is very little a priori information about hypothesized RNA structures, the number of motif ‘hits’ may become very large. Exhaustive methods to search for similar RNA structures over these large search spaces are likely to be computationally intractable. Here we describe a powerful new algorithm based on evolutionary computation to solve this problem. A series of experiments using ferritin IRE and SRP RNA stem–loop motifs were used to verify the method. We demonstrate that even when searching extremely large search spaces, of the order of 1023 potential solutions, we could find the correct solution in a fraction of the time it would have taken for exhaustive comparisons.


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