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

doi:10.1093/bioinformatics/btr474

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

Biostatistics

Research output: Contribution to journal › Article › peer-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 language	English
Article number	btr474
Pages (from-to)	2775-2781
Number of pages	7
Journal	Bioinformatics
Volume	27
Issue number	20
DOIs	https://doi.org/10.1093/bioinformatics/btr474
State	Published - 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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Zhang, X. D., Santini, F., Lacson, R., Marine, S. D., Wu, Q., Benetti, L., Yang, R., McCampbell, A., Berger, J. P., Toolan, D. M., Stec, E. M., Holder, D. J., Soper, K. A., Heyse, J. F., & Ferrer, M. (2011). cSSMD: Assessing collective activity for addressing off-target effects in genome-scale RNA interference screens. Bioinformatics, 27(20), 2775-2781. Article btr474. https://doi.org/10.1093/bioinformatics/btr474

@article{63efa00cf63142fc86f34021cbdf9102,

title = "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.",

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

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",

year = "2011",

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doi = "10.1093/bioinformatics/btr474",

language = "English",

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Zhang, XD, Santini, F, Lacson, R, Marine, SD, Wu, Q, Benetti, L, Yang, R, McCampbell, A, Berger, JP, Toolan, DM, Stec, EM, Holder, DJ, Soper, KA, Heyse, JF & Ferrer, M 2011, 'cSSMD: Assessing collective activity for addressing off-target effects in genome-scale RNA interference screens', Bioinformatics, vol. 27, no. 20, btr474, pp. 2775-2781. https://doi.org/10.1093/bioinformatics/btr474

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T2 - Assessing collective activity for addressing off-target effects in genome-scale RNA interference screens

AU - Zhang, Xiaohua Douglas

AU - Santini, Francesca

AU - Lacson, Raul

AU - Marine, Shane D.

AU - Wu, Qian

AU - Benetti, Luca

AU - Yang, Ruojing

AU - McCampbell, Alex

AU - Berger, Joel P.

AU - Toolan, Dawn M.

AU - Stec, Erica M.

AU - Holder, Daniel J.

AU - Soper, Keith A.

AU - Heyse, Joseph F.

AU - Ferrer, Marc

N1 - 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

PY - 2011/10

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N2 - 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.

AB - 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.

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

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Bibliographical note

ASJC Scopus subject areas

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