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CSSMD: assessing collective activity for addressing off-target effects in genome-scale RNA interference screens.


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. CONTACT: xiaohua_zhang@merck.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUBMITTER: Zhang XD 

PROVIDER: S-EPMC3202303 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Zhang Xiaohua Douglas XD   Santini Francesca F   Lacson Raul R   Marine Shane D SD   Wu Qian Q   Benetti Luca L   Yang Ruojing R   McCampbell Alex A   Berger Joel P JP   Toolan Dawn M DM   Stec Erica M EM   Holder Daniel J DJ   Soper Keith A KA   Heyse Joseph F JF   Ferrer Marc M  

Bioinformatics (Oxford, England) 20110816 20


<h4>Motivation</h4>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.<h4>Results</h4>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 spe  ...[more]

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