Developing chemical in vitro-in vivo correlations (IVIVCs) between ARE pathway activation and hepatotoxicity.
In vitro assays have been used as an alternative to evaluate hepatotoxicity. However, the combination of in vitro and in vivo evaluations have not successfully replaced in vivo hepatotoxicity models.
The QSAR model based on the qHTS ARE-bla data sets can be used to predict the ARE activation when ARE experimental result is not available.
The active responses obtained from the biological response profiling can suggest potential hepatotoxicity.
qHTS ARE-bla data set, In vivo hepatotoxicity data set, qHTS assay to identify small-molecule antagonists of the TR signaling pathway, qHTS assay to identify small-molecule agonists of the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway, and qHTS for inhibitors of TDP1.
QSAR (quantitative structure activity relationship) models are regression or classification models used in the chemical and biological sciences and engineering, which relate a set of predictor variables to a response variable.
PCA (principal component analysis) is a statistical procedure that uses an orthogonal transformation to convert a set of observations of possibly correlated variables into a set of values of linearly uncorrelated variables called principal components.
AOP (adverse outcome pathways) is a logical sequence of biological responses that is useful for understanding complex toxicity phenomena.
ARE activation can be predicted by QSAR model based on qHTS ARE-bla data sets.
Prediction of compounds outside the applicability domain is not as accurate as compounds within applicability domain.
Point of view
Profiling chemical IVIVCs created an opportunity to fully explore the source-to-outcome continuum of modern experimental toxicology using cheminformatics approaches and big data sources.
The QSAR model based on the qHTS ARE-bla dataset can be applied to other biological assays.
The workflow that identified assays from a public big data source can be used to evaluate liver damage caused by oxidative stress.