Issues of Z-factor and an approach to avoid them for quality control in high-throughput screening studies

Xiaohua Douglas Zhang, Dandan Wang, Shixue Sun, Heping Zhang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Motivation: High-throughput screening (HTS) is a vital automation technology in biomedical research in both industry and academia. The well-known Z-factor has been widely used as a gatekeeper to assure assay quality in an HTS study. However, many researchers and users may not have realized that Z-factor has major issues. Results: In this article, the following four major issues are explored and demonstrated so that researchers may use the Z-factor appropriately. First, the Z-factor violates the Pythagorean theorem of statistics. Second, there is no adjustment of sampling error in the application of the Z-factor for quality control (QC) in HTS studies. Third, the expectation of the sample-based Z-factor does not exist. Fourth, the thresholds in the Z-factor-based criterion lack a theoretical basis. Here, an approach to avoid these issues was proposed and new QC criteria under homoscedasticity were constructed so that researchers can choose a statistically grounded criterion for QC in the HTS studies. We implemented this approach in an R package and demonstrated its utility in multiple CRISPR/CAS9 or siRNA HTS studies.

Original languageEnglish
Pages (from-to)5299-5303
Number of pages5
Issue number22-23
StatePublished - Dec 1 2020

Bibliographical note

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© 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail:

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics


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