title: Accounting Artifacts in High-Throughput Toxicity Assays.
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.
authors: Kelly Government Solutions Supporting NTP, 530 Davis Dr., Morrisville, NC, 27560, USA. jui-hua.hsieh@nih.gov.
authors: Jui-Hua
authors: JH
authors: Hsieh
mesh_terms: D000465:Algorithms; D016477:Artifacts; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D017930:Genes, Reporter; D057166:High-Throughput Screening Assays / Q000592:standards*; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D059629:Signal-To-Noise Ratio; D015262:Xenobiotics / Q000633:toxicity*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D011965:Receptors, Glucocorticoid; D015262:Xenobiotics; D001618:beta-Lactamases
keywords: Assay artifacts; Concentration-response data; Data analysis pipeline; HTS; Point-of-departure; Tox21; qHTS