Citation:

Baker, N., N. Sipes, J. Franzosa, D. Belair, B. Abbott, R. Judson, AND T. Knudsen. Characterizing cleft palate toxicants using ToxCast data, chemical structure, and the biomedical literature. Birth Defects Research. John Wiley & Sons, Inc., Hoboken, NJ, , 1-21, (2019). https://doi.org/10.1002/bdr2.1581

Impact/Purpose:

Connecting cleft palate toxicant information toward predicting cleft palate.

Description:

Cleft palate has been linked to both genetic and environmental factors that perturb key events during palatal morphogenesis. To characterize the potential molecular targets for chemical-induced cleft palate, we mined the ToxCast high-throughput screening (HTS) database for patterns and linkages in bioactivity profiles and chemical structural descriptors. ToxCast assay results were filtered for cytotoxicity and summarized by gene for use by informatics and machine-learning methods that discriminated between 63 cleft palate active chemicals and 437 chemicals not found to induce cleft palate in animal prenatal developmental studies from the ToxRefDB and biomedical literature. Hierarchical clustering partitioned the 63 cleft palate positives into local bioactivity clusters for in vitro effects on ToxCast assays for cytochrome P450s, G protein-coupled receptors, retinoic acid receptors, the glucocorticoid receptor, and tyrosine kinases/phosphatases. Decision trees and putative AOPs for cleft palate were then constructed from the in vitro profiling data combined with chemical structural information in an approach that can be generalized for other developmental end points.

URLs/Downloads:

Record Details: