A Statistical Method Assessing Collective Activity of Multiple siRNAs Targeting a Gene in RNAi Screens

• Activity Number: 515
• Type: Contributed
• Date/Time: Wednesday, August 4, 2010 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Xiaohua Douglas Zhang*+
• Companies: Merck Research Laboratories
• Keywords: off-target effect ; high-throughput screening ; strictly standardized mean difference ; effect size ; collective activity ; specific activity

Abstract

In RNAi high-throughput screens, false positives generated by off-specific effects can lead to the use of resources to explore non-productive research tracts. The popular approach to address off-target effects is to test multiple siRNAs with different sequences against a target gene. The corresponding analytic methods include frequency approach, redundant siRNA activity method and RNAi gene enrichment ranking method. All these methods do not assess the size of collective activity of multiple siRNAs. Here I theoretically derive a statistical method assessing this collective activity. This method captures both the average value and variability of measured responses of siRNAs targeting a gene. In addition,it can assess the specific effect of an siRNA relative to the collective effects of all siRNAs targeting the same gene which provides a reference about the size of off-target effects.