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

doi:10.1093/nar/gku306

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 journal › Article › peer-review

19 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 language	English (US)
Pages (from-to)	8214-8222
Number of pages	9
Journal	Nucleic acids research
Volume	42
Issue number	13
DOIs	https://doi.org/10.1093/nar/gku306
State	Published - Jul 29 2014

ASJC Scopus subject areas

Genetics

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

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.",

author = "Rui Zhong and Jimi Kim and Kim, {Hyun Seok} and Minsoo Kim and Lawrence Lum and Beth Levine and Guanghua Xiao and White, {Michael A.} and Yang Xie",

note = "Funding Information: National Institutes of Health (NIH) [5R01CA152301, P50CA70907 and 5P30CA142543 to R.Z. and Y.X.; 1R01CA172211 and 4R33DA027592 to Y.X. and G.X.; CA071444, CA148225 and CA176284 to M.W.; CA109618 to B.L.]; National Aeronautics and Space Administration [NNJ05HD36G to Y.X.]; Welch Foundation [I-1414 to M.W.]; Cancer Prevention and Research Institute of Texas [RP120718 to M.W. and B.L.; RP120732 to Y.X. and G.X.; RP101496 to H.K.]. Funding for open access charge: NIH 5R01CA152301. Conflict of interest statement. None declared.",

year = "2014",

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doi = "10.1093/nar/gku306",

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AU - Zhong, Rui

AU - Kim, Jimi

AU - Kim, Hyun Seok

AU - Kim, Minsoo

AU - Lum, Lawrence

AU - Levine, Beth

AU - Xiao, Guanghua

AU - White, Michael A.

AU - Xie, Yang

N1 - Funding Information: National Institutes of Health (NIH) [5R01CA152301, P50CA70907 and 5P30CA142543 to R.Z. and Y.X.; 1R01CA172211 and 4R33DA027592 to Y.X. and G.X.; CA071444, CA148225 and CA176284 to M.W.; CA109618 to B.L.]; National Aeronautics and Space Administration [NNJ05HD36G to Y.X.]; Welch Foundation [I-1414 to M.W.]; Cancer Prevention and Research Institute of Texas [RP120718 to M.W. and B.L.; RP120732 to Y.X. and G.X.; RP101496 to H.K.]. Funding for open access charge: NIH 5R01CA152301. Conflict of interest statement. None declared.

PY - 2014/7/29

Y1 - 2014/7/29

N2 - 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.

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

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