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

Zhong R, Kim J, Kim HS, Kim M, Lum L, Levine B, Xiao G, White MA, Xie Y

Nucleic Acids Research

June 27, 2014

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. (Publication Abstract)

Last updated: June 29, 2020