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The use of strictly standardized mean difference for hit selection in primary RNA interference high-throughput screening experiments
Zhang X.D.1; Ferrer M.1; Espeseth A.S.1; Marine S.D.1; Stec E.M.1; Crackower M.A.2; Holder D.J.1; Heyse J.F.1; Strulovici B.1
2007-06-01
Source PublicationJournal of Biomolecular Screening
ISSN10870571 1552454X
Volume12Issue:4Pages:497-509
Abstract

RNA interference (RNAi) high-throughput screening (HTS) has been hailed as the 2nd genomics wave following the 1st genomics wave of gene expression microarrays and single-nucleotide polymorphism discovery platforms. Following an RNAi HTS, the authors are interested in identifying short interfering RNA (siRNA) hits with large inhibition/activation effects. For hit selection, the z-score method and its variants are commonly used in primary RNAi HTS experiments. Recently, strictly standardized mean difference (SSMD) has been proposed to measure the siRNA effect represented by the magnitude of difference between an siRNA and a negative reference group. The links between SSMD and d-probability offer a clear interpretation of siRNA effects from a probability perspective. Hence, SSMD can be used as a ranking metric for hit selection. In this article, the authors investigated both the SSMD-based testing process and the use of SSMD as a ranking metric for hit selection in 2 primary siRNA HTS experiments. The analysis results showed that, as a ranking metric, SSMD was more stable and reliable than percentage inhibition and led to more robust hit selection results. Using the SSMD -based testing method, the false-negative rate can more readily be obtained. More important, the use of the SSMD-based method can result in a reduction in both the false-negative and false-positive rates. The applications presented in this article demonstrate that the SSMD method addresses scientific questions and fills scientific needs better than both percentage inhibition and the commonly used z-score method for hit selection. © 2007 Society for Biomolecular Sciences.

Keywordd+-probability High-throughput Screening Hit Rate Point Restricted False-positive Rate Strictly Standardized Mean Difference
DOI10.1177/1087057107300646
URLView the original
Indexed BySCI
Language英语
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Cited Times [WOS]:60   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Merck Research Laboratories
2.Merck Frosst
Recommended Citation
GB/T 7714
Zhang X.D.,Ferrer M.,Espeseth A.S.,et al. The use of strictly standardized mean difference for hit selection in primary RNA interference high-throughput screening experiments[J]. Journal of Biomolecular Screening,2007,12(4):497-509.
APA Zhang X.D..,Ferrer M..,Espeseth A.S..,Marine S.D..,Stec E.M..,...&Strulovici B..(2007).The use of strictly standardized mean difference for hit selection in primary RNA interference high-throughput screening experiments.Journal of Biomolecular Screening,12(4),497-509.
MLA Zhang X.D.,et al."The use of strictly standardized mean difference for hit selection in primary RNA interference high-throughput screening experiments".Journal of Biomolecular Screening 12.4(2007):497-509.
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