Integration of multiple readouts into the z' factor for assay quality assessment

Journal of Biomolecular Screening
Anne KümmelChristian N Parker

Abstract

Methods that monitor the quality of a biological assay (i.e., its ability to discriminate between positive and negative controls) are essential for the development of robust assays. In screening, the most commonly used parameter for monitoring assay quality is the Z' factor, which is based on 1 selected readout. However, biological assays are able to monitor multiple readouts. For example, novel multiparametric screening technologies such as high-content screening provide information-rich data sets with multiple readouts on a compound's effect. Still, assay quality is commonly assessed by the Z' factor based on a single selected readout. This report suggests an extension of the Z' factor, which integrates multiple readouts for assay quality assessment. Using linear projections, multiple readouts are condensed to a single parameter, based on which the assay quality is monitored. The authors illustrate and evaluate this approach using simulated data and real-world data from a high-content screen. The suggested approach is applicable during assay development, to optimize the image analysis, as well as during screening to monitor assay robustness. Furthermore, data sets from high-content imaging assays and other state-of-the-art mu...Continue Reading

References

Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Jan 16, 2007·Journal of Biomolecular Screening·Yunxia Sui, Zhijin Wu
Dec 19, 2007·Journal of Biomolecular Screening·Oliver DürrDominique Besson

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Citations

Dec 4, 2012·Assay and Drug Development Technologies·Bhavneet BhinderHakim Djaballah
Jun 26, 2010·Analytical and Bioanalytical Chemistry·Marc Bickle
Aug 7, 2012·Expert Opinion on Drug Discovery·Susanne Heynen-GenelJonathan Rosen
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Aug 24, 2016·Assay and Drug Development Technologies·Scott J WarchalNeil O Carragher
Feb 22, 2014·Journal of Biomolecular Screening·Milan EsnerMarc Bickle
Sep 21, 2013·Journal of Biomolecular Screening·Hind AzegrouzMaría C Montoya
Apr 9, 2014·Journal of Biomolecular Screening·Shantanu SinghAuguste Genovesio
Mar 7, 2014·Journal of Biomolecular Screening·Yann AbrahamChristian N Parker
Nov 24, 2011·Nature Communications·Stefano TizianiGiovanni Paternostro
Sep 1, 2017·Nature Methods·Juan C CaicedoAnne E Carpenter
Nov 4, 2016·Nature Reviews. Drug Discovery·Peter HorvathNeil O Carragher
Jun 19, 2012·Journal of Biomolecular Screening·Teresa Fernández-AceroVíctor J Cid
Jun 23, 2011·Journal of Biomolecular Screening·Marie-Cecile DidiotChristian N Parker
Feb 22, 2011·Journal of Biomolecular Screening·Anne KümmelDaniela Gabriel
Sep 22, 2016·Journal of Biomolecular Screening·Maria MontoyaMarc Bickle
Jul 30, 2020·Pharmaceuticals·Sven Bulterijs, Bart P Braeckman
Feb 6, 2020·The Journal of Antimicrobial Chemotherapy·Samantha A MichaelsKayode K Ojo
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Dec 21, 2021·ACS Pharmacology & Translational Science·Renna K E CostaSandra M G Dias

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