Computational detection and suppression of sequence-specific off-target phenotypes from whole genome RNAi screens

Rui Zhong, Jimi Kim, Hyun Seok Kim, Minsoo Kim, Lawrence Lum, Beth Levine, Guanghua Xiao, Michael A. White, Yang Xie

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

A challenge for large-scale siRNA loss-of-function studies is the biological pleiotropy resulting from multiple modes of action of siRNA reagents. A major confounding feature of these reagents is the microRNA-like translational quelling resulting from short regions of oligonucleotide complementarity to many different messenger RNAs. We developed a computational approach, deconvolution analysis of RNAi screening data, for automated quantitation of off-target effects in RNAi screening data sets. Substantial reduction of off-target rates was experimentally validated in five distinct biological screens across different genome-wide siRNA libraries. A public-access graphical-user-interface has been constructed to facilitate application of this algorithm.

Original languageEnglish (US)
Pages (from-to)8214-8222
Number of pages9
JournalNucleic acids research
Volume42
Issue number13
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Genetics

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