cSSMD: Assessing collective activity for addressing off-target effects in genome-scale RNA interference screens

Xiaohua Douglas Zhang, Francesca Santini, Raul Lacson, Shane D. Marine, Qian Wu, Luca Benetti, Ruojing Yang, Alex McCampbell, Joel P. Berger, Dawn M. Toolan, Erica M. Stec, Daniel J. Holder, Keith A. Soper, Joseph F. Heyse, Marc Ferrer

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Motivation: Off-target activity commonly exists in RNA interference (RNAi) screens and often generates false positives. Existing analytic methods for addressing the off-target effects are demonstrably inadequate in RNAi confirmatory screens. Results: Here, we present an analytic method assessing the collective activity of multiple short interfering RNAs (siRNAs) targeting a gene. Using this method, we can not only reduce the impact of off-target activities, but also evaluate the specific effect of an siRNA, thus providing information about potential off-target effects. Using in-house RNAi screens, we demonstrate that our method obtains more reasonable and sensible results than current methods such as the redundant siRNA activity (RSA) method, the RNAi gene enrichment ranking (RIGER) method, the frequency approach and the t-test.

Original languageEnglish
Article numberbtr474
Pages (from-to)2775-2781
Number of pages7
JournalBioinformatics
Volume27
Issue number20
DOIs
StatePublished - Oct 2011

Bibliographical note

Funding Information:
1Biometrics Research, Merck Research Laboratories, West Point, PA 19486, 2Automated Biotechnology, Merck Research Laboratories, North Wales, PA 19454, 3Biostatistics, University of Pennsylvania, Philadelphia, PA, 4Vaccine Manufacturing Sciences and Commercialization, Merck Manufacturing Division, West Point, PA 19486, 5Diabetes, Merck Research Laboratories, Rahway, NJ 07065, 6Neurology, Merck Research Laboratories, West Point, PA 19486, 7BARDS, Merck Research Laboratories, West Point, PA 19486 and 8Chemical Genomics Center, National Institutes of Health, Rockville, MD, USA

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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