title: The use of SSMD-based false discovery and false nondiscovery rates in genome-scale RNAi screens.
abstract: In genome-scale RNA interference (RNAi) screens, it is critical to control false positives and false negatives statistically. Traditional statistical methods for controlling false discovery and false nondiscovery rates are inappropriate for hit selection in RNAi screens because the major goal in RNAi screens is to control both the proportion of short interfering RNAs (siRNAs) with a small effect among selected hits and the proportion of siRNAs with a large effect among declared nonhits. An effective method based on strictly standardized mean difference (SSMD) has been proposed for statistically controlling false discovery rate (FDR) and false nondiscovery rate (FNDR) appropriate for RNAi screens. In this article, the authors explore the utility of the SSMD-based method for hit selection in RNAi screens. As demonstrated in 2 genome-scale RNAi screens, the SSMD-based method addresses the unmet need of controlling for the proportion of siRNAs with a small effect among selected hits, as well as controlling for the proportion of siRNAs with a large effect among declared nonhits. Furthermore, the SSMD-based method results in reasonably low FDR and FNDR for selecting inhibition or activation hits. This method works effectively and should have a broad utility for hit selection in RNAi screens with replicates.
authors.affiliation: Biometrics Research, Merck Research Laboratories, West Point, PA 19486, USA. xiaohua_zhang@merck.com
authors.forename: Xiaohua Douglas
authors.initials: XD
authors.lastname: Zhang
authors.forename: Raul
authors.initials: R
authors.lastname: Lacson
authors.forename: Ruojing
authors.initials: R
authors.lastname: Yang
authors.forename: Shane D
authors.initials: SD
authors.lastname: Marine
authors.forename: Alex
authors.initials: A
authors.lastname: McCampbell
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Toolan
authors.forename: Tim R
authors.initials: TR
authors.lastname: Hare
authors.forename: Joleen
authors.initials: J
authors.lastname: Kajdas
authors.forename: Joel P
authors.initials: JP
authors.lastname: Berger
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Holder
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Heyse
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrer
mesh_terms: D045744:Cell Line, Tumor; D003920:Diabetes Mellitus / Q000235:genetics; D005188:False Negative Reactions; D005189:False Positive Reactions; D016678:Genome / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D006801:Humans; D009422:Nervous System Diseases / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D034741:RNA, Small Interfering