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Genome Res DOI:10.1101/gr.143586.112

ATARiS: computational quantification of gene suppression phenotypes from multisample RNAi screens.

Publication TypeJournal Article
Year of Publication2013
AuthorsShao, DD, Tsherniak, A, Gopal, S, Weir, BA, Tamayo, P, Stransky, N, Schumacher, SE, Zack, TI, Beroukhim, R, Garraway, LA, Margolin, AA, Root, DE, Hahn, WC, Mesirov, JP
JournalGenome Res
Volume23
Issue4
Pages665-78
Date Published2013 Apr
ISSN1549-5469
KeywordsAnimals, Cell Transformation, Neoplastic, Computational Biology, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genomics, Hepatocyte Nuclear Factor 1-beta, Humans, Internet, Mice, Neoplasms, Phenotype, Reproducibility of Results, RNA Interference, RNA, Small Interfering, Software
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.

URLhttp://genome.cshlp.org/cgi/pmidlookup?view=long&pmid=23269662
DOI10.1101/gr.143586.112
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23269662?dopt=Abstract

Alternate JournalGenome Res.
PubMed ID23269662
PubMed Central IDPMC3613583
Grant ListR01 GM074024 / GM / NIGMS NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
U54CA112962 / CA / NCI NIH HHS / United States
R01 CA109467 / CA / NCI NIH HHS / United States
U54 CA112962 / CA / NCI NIH HHS / United States
RC2 CA148268 / CA / NCI NIH HHS / United States
P01 CA050661 / CA / NCI NIH HHS / United States