Title: RNA string kernels for RNAi off-target evaluation

Authors: Shibin Qiu, Terran Lane

Addresses: Department of Computer Science, The University of New Mexico, Albuquerque, NM 87131, USA. ' Department of Computer Science, The University of New Mexico, Albuquerque, NM 87131, USA

Abstract: RNA interference (RNAi) is a posttranscriptional gene silencing mechanism used to study gene functions, knock down viral genes, and treat diseases therapeutically. However, an |off-target effect| deteriorates its specificity and applicability. Complete off-target effects can only be characterised by examining each gene in a genome, which is too expensive to conduct experimentally and motivates a computational study. To simulate the sequence matching between an siRNA and its target mRNA allowing for mismatches, G-U wobbles and bulges, we propose string kernels and develop their efficient implementations for off-target detection. We evaluate RNAi specificities in Schizosaccharomyces pombe, Caenorhabdithis elegans, and human genomes.

Keywords: RNA interference; RNAi; siRNA; dsRNA; mRNA; specificity; off-target knockdown; string kernels; sequence similarity; mismatch wobble; mismatch bulge; genome wide search; genome retrieval; off-target detection; gene silencing; viral genes; disease treatment; bioinformatics; pattern control.

DOI: 10.1504/IJBRA.2006.009764

International Journal of Bioinformatics Research and Applications, 2006 Vol.2 No.2, pp.132 - 146

Published online: 09 May 2006 *

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