TY - JOUR
T1 - The use of SSMD-based false discovery and false nondiscovery rates in genome-scale RNAi screens
AU - Zhang, Xiaohua Douglas
AU - Lacson, Raul
AU - Yang, Ruojing
AU - Marine, Shane D.
AU - McCampbell, Alex
AU - Toolan, Dawn M.
AU - Hare, Tim R.
AU - Kajdas, Joleen
AU - Berger, Joel P.
AU - Holder, Daniel J.
AU - Heyse, Joseph F.
AU - Ferrer, Marc
PY - 2010/10
Y1 - 2010/10
N2 - 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.
AB - 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.
KW - -value
KW - RNAi
KW - false discovery rate
KW - false nondiscovery rate
KW - high-throughput screening
KW - p
KW - q
UR - http://www.scopus.com/inward/record.url?scp=78650116448&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650116448&partnerID=8YFLogxK
U2 - 10.1177/1087057110381919
DO - 10.1177/1087057110381919
M3 - Article
C2 - 20852024
AN - SCOPUS:78650116448
SN - 1087-0571
VL - 15
SP - 1123
EP - 1131
JO - Journal of Biomolecular Screening
JF - Journal of Biomolecular Screening
IS - 9
ER -