RNA string kernels for RNAi off-target evaluation

Int J Bioinform Res Appl. 2006;2(2):132-46. doi: 10.1504/IJBRA.2006.009764.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Animals
  • Caenorhabditis elegans
  • Computational Biology / methods*
  • Genome
  • Genome, Human
  • Humans
  • Models, Statistical
  • RNA / chemistry*
  • RNA Interference*
  • RNA, Double-Stranded / chemistry
  • RNA, Small Interfering / metabolism
  • Schizosaccharomyces / metabolism
  • Sensitivity and Specificity
  • Software

Substances

  • RNA, Double-Stranded
  • RNA, Small Interfering
  • RNA