title: ATARiS: computational quantification of gene suppression phenotypes from multisample RNAi screens.
abstract: Genome-scale RNAi libraries enable the systematic interrogation of gene function. However, the interpretation of RNAi screens is complicated by the observation that RNAi reagents designed to suppress the mRNA transcripts of the same gene often produce a spectrum of phenotypic outcomes due to differential on-target gene suppression or perturbation of off-target transcripts. Here we present a computational method, Analytic Technique for Assessment of RNAi by Similarity (ATARiS), that takes advantage of patterns in RNAi data across multiple samples in order to enrich for RNAi reagents whose phenotypic effects relate to suppression of their intended targets. By summarizing only such reagent effects for each gene, ATARiS produces quantitative, gene-level phenotype values, which provide an intuitive measure of the effect of gene suppression in each sample. This method is robust for data sets that contain as few as 10 samples and can be used to analyze screens of any number of targeted genes. We used this analytic approach to interrogate RNAi data derived from screening more than 100 human cancer cell lines and identified HNF1B as a transforming oncogene required for the survival of cancer cells that harbor HNF1B amplifications. ATARiS is publicly available at http://broadinstitute.org/ataris.
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
authors.forename: Diane D
authors.initials: DD
authors.lastname: Shao
authors.forename: Aviad
authors.initials: A
authors.lastname: Tsherniak
authors.forename: Shuba
authors.initials: S
authors.lastname: Gopal
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Weir
authors.forename: Pablo
authors.initials: P
authors.lastname: Tamayo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stransky
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schumacher
authors.forename: Travis I
authors.initials: TI
authors.lastname: Zack
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.forename: Adam A
authors.initials: AA
authors.lastname: Margolin
authors.forename: David E
authors.initials: DE
authors.lastname: Root
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.forename: Jill P
authors.initials: JP
authors.lastname: Mesirov
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D006801:Humans; D020407:Internet; D051379:Mice; D009369:Neoplasms / Q000235:genetics; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D015203:Reproducibility of Results; D012984:Software
chemical_list: C496495:HNF1B protein, human; D034741:RNA, Small Interfering; D051539:Hepatocyte Nuclear Factor 1-beta