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.
authors: Quantitative Biomedical Research Center, Dallas, TX, USA Department of Clinical Sciences, Dallas, TX, USA.
authors: Rui
authors: R
authors: Zhong
authors: Department of Cell Biology, Dallas, TX, USA.
authors: Jimi
authors: J
authors: Kim
authors: Department of Cell Biology, Dallas, TX, USA Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors: Hyun Seok
authors: HS
authors: Kim
authors: Quantitative Biomedical Research Center, Dallas, TX, USA Department of Clinical Sciences, Dallas, TX, USA Simmons Comprehensive Cancer Center, Dallas, TX, USA.
authors: Minsoo
authors: M
authors: Kim
authors: Department of Cell Biology, Dallas, TX, USA.
authors: Lawrence
authors: L
authors: Lum
authors: Center for Autophagy Research, Dallas, TX, USA Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX, USA.
authors: Beth
authors: B
authors: Levine
authors: Quantitative Biomedical Research Center, Dallas, TX, USA Department of Clinical Sciences, Dallas, TX, USA.
authors: Guanghua
authors: G
authors: Xiao
authors: Department of Cell Biology, Dallas, TX, USA Yang.Xie@utsouthwestern.edu.
authors: Michael A
authors: MA
authors: White
authors: Quantitative Biomedical Research Center, Dallas, TX, USA Department of Clinical Sciences, Dallas, TX, USA Yang.Xie@utsouthwestern.edu.
authors: Yang
authors: Y
authors: Xie
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D002460:Cell Line; D023281:Genomics / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering