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Accounting Artifacts in High-Throughput Toxicity Assays

  • Jui-Hua HsiehEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1473)

Abstract

Compound activity identification is the primary goal in high-throughput screening (HTS) assays. However, assay artifacts including both systematic (e.g., compound auto-fluorescence) and nonsystematic (e.g., noise) complicate activity interpretation. In addition, other than the traditional potency parameter, half-maximal effect concentration (EC50), additional activity parameters (e.g., point-of-departure, POD) could be derived from HTS data for activity profiling. A data analysis pipeline has been developed to handle the artifacts and to provide compound activity characterization with either binary or continuous metrics. This chapter outlines the steps in the pipeline using Tox21 glucocorticoid receptor (GR) β-lactamase assays, including the formats to identify either agonists or antagonists, as well as the counter-screen assays for identifying artifacts as examples. The steps can be applied to other lower-throughput assays with concentration-response data.

Key words

HTS qHTS Concentration-response data Tox21 Assay artifacts Data analysis pipeline Point-of-departure 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Kelly Government Solutions Supporting NTPMorrisvilleUSA

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