title: Integrating experimental and analytic approaches to improve data quality in genome-wide RNAi screens.
abstract: RNA interference (RNAi) not only plays an important role in drug discovery but can also be developed directly into drugs. RNAi high-throughput screening (HTS) biotechnology allows us to conduct genome-wide RNAi research. A central challenge in genome-wide RNAi research is to integrate both experimental and computational approaches to obtain high quality RNAi HTS assays. Based on our daily practice in RNAi HTS experiments, we propose the implementation of 3 experimental and analytic processes to improve the quality of data from RNAi HTS biotechnology: (1) select effective biological controls; (2) adopt appropriate plate designs to display and/or adjust for systematic errors of measurement; and (3) use effective analytic metrics to assess data quality. The applications in 5 real RNAi HTS experiments demonstrate the effectiveness of integrating these processes to improve data quality. Due to the effectiveness in improving data quality in RNAi HTS experiments, the methods and guidelines contained in the 3 experimental and analytic processes are likely to have broad utility in genome-wide RNAi research.
authors.affiliation: Biometrics Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. xiaohua_zhang@merck.com
authors.forename: Xiaohua Douglas
authors.initials: XD
authors.lastname: Zhang
authors.forename: Amy S
authors.initials: AS
authors.lastname: Espeseth
authors.forename: Eric N
authors.initials: EN
authors.lastname: Johnson
authors.forename: Jayne
authors.initials: J
authors.lastname: Chin
authors.forename: Adam
authors.initials: A
authors.lastname: Gates
authors.forename: Lyndon J
authors.initials: LJ
authors.lastname: Mitnaul
authors.forename: Shane D
authors.initials: SD
authors.lastname: Marine
authors.forename: Jenny
authors.initials: J
authors.lastname: Tian
authors.forename: Eric M
authors.initials: EM
authors.lastname: Stec
authors.forename: Priya
authors.initials: P
authors.lastname: Kunapuli
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Holder
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Heyse
authors.forename: Berta
authors.initials: B
authors.lastname: Strulovici
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrer
mesh_terms: D016632:Apolipoprotein A-I / Q000235:genetics; D001709:Biotechnology / Q000379:methods* / Q000592:standards; D016678:Genome; D016174:Hepacivirus / Q000235:genetics; D011786:Quality Control; D034622:RNA Interference; D012107:Research Design / Q000592:standards
chemical_list: D016632:Apolipoprotein A-I