RNA string kernels for RNAi off-target evaluation

Authors:
Shibin Qiu;Terran Lane
Affiliations:
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
Venue:
International Journal of Bioinformatics Research and Applications
Year:
2006

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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.