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

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.

Source: Nucleic Acids Research - July 31, 2014 Category: Research Authors: Zhong, R., Kim, J., Kim, H. S., Kim, M., Lum, L., Levine, B., Xiao, G., White, M. A., Xie, Y. Tags: Computational Methods, Targeted inhibition of gene function Computational Biology Source Type: research