The use of SSMD-based false discovery and false nondiscovery rates in genome-scale RNAi screens

Xiaohua Douglas Zhang, Raul Lacson, Ruojing Yang, Shane D. Marine, Alex McCampbell, Dawn M. Toolan, Tim R. Hare, Joleen Kajdas, Joel P. Berger, Daniel J. Holder, Joseph F. Heyse, Marc Ferrer

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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 (siR-NAs) 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.

Original languageEnglish
Pages (from-to)1123-1131
Number of pages9
JournalJournal of Biomolecular Screening
Volume15
Issue number9
DOIs
StatePublished - Oct 2010

Keywords

  • -value
  • RNAi
  • false discovery rate
  • false nondiscovery rate
  • high-throughput screening
  • p
  • q

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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