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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.

SUBMITTER: Zhong R 

PROVIDER: S-EPMC4117740 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Zhong Rui R   Kim Jimi J   Kim Hyun Seok HS   Kim Minsoo M   Lum Lawrence L   Levine Beth B   Xiao Guanghua G   White Michael A MA   Xie Yang Y  

Nucleic acids research 20140627 13


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. S  ...[more]

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