title: A pair of new statistical parameters for quality control in RNA interference high-throughput screening assays.
abstract: RNA interference (RNAi) high-throughput screening (HTS) enables massive parallel gene silencing and is increasingly being used to reveal novel connections between genes and disease-relevant phenotypes. The application of genome-scale RNAi relies on the development of high-quality RNAi HTS assays. To obtain high-quality HTS assays, there is a strong need for an easily interpretable and theoretically based quality control (QC) metric. Signal-to-noise ratio (S/N), signal-to-background ratio (S/B), and Z-factor have been adopted as QC metrics in HTS assays. In this paper, I proposed a pair of new parameters, strictly standardized mean difference (SSMD) and coefficient of variability in difference (CVD), as QC metrics in RNAi HTS assays. Compared to S/B and S/N, SSMD and CVD capture the variabilities in both compared populations. Compared to Z-factor, SSMD and CVD have a clear probability interpretation and a solid statistical basis. Accordingly, the cutoff criteria of using SSMD or CVD as a QC metric in HTS assays are fully theoretically based. In addition, I discuss the relationship between the SSMD-based criterion and the popular Z-factor-based criterion and elucidate why p-value from t-test of testing mean difference fails to serve as a QC metric.
authors.affiliation: Biometrics Research, Merck Research Laboratories, West Point, PA 19486, USA. xiaohua_zhang@merck.com
authors.forename: Xiaohua Douglas
authors.initials: XD
authors.lastname: Zhang
mesh_terms: D020868:Gene Silencing; D005820:Genetic Testing / Q000379:methods*; D008722:Methods; D015233:Models, Statistical; D008962:Models, Theoretical; D011786:Quality Control; D034622:RNA Interference