Nuclear receptors (NRs) play critical roles in human development, metabolic homeostasis and reproduction. Inappropriate activation of nuclear receptors by environmental chemicals can lead to a broad spectrum of negative health effects. To evaluate environmental chemicals’ effects on endocrine disruption, Tox21 researchers have selected appropriate NR assays for quantitative high-throughput screening (qHTS).
As a proof-of-concept study, researchers profiled in qHTS format approximately 3,000 environmental chemicals against a panel of 10 human NRs during the Tox21 pilot phase. The team evaluated these data from a chemical genomics point of view, in addition to assessing data reproducibility as a measure of data quality and applicability for down-stream analyses.
This graphic describes how NRs interact with genes. NRs recognize small hormones or synthetic (man-made) compounds. Each NR activates genes that cooperate to change human physiology.
This graphic shows example structure classes with consistent NR activity patterns or signatures. Compounds were clustered by similar structure using the SOM algorithm. Compounds in the same cluster belong to the same structure class. The structure classes shown in this figure contain compounds with similar activity patterns as well.