You are here:
Causal Inferences from Mining ToxCast Data and the Biomedical Literature for Molecular Pathways and Cellular Processes in Cleft Palate (SOT)
Baker, N., N. Sipes, Chris Grulke, R. Judson, AND T. Knudsen. Causal Inferences from Mining ToxCast Data and the Biomedical Literature for Molecular Pathways and Cellular Processes in Cleft Palate (SOT). Presented at SOT Annual Meeting, San Diego, CA, March 22 - 26, 2015. https://doi.org/10.23645/epacomptox.5178751
Present poster at SOT meeting in San Diego, CA on March 24, 2015
Sixty-five chemicals in the ToxCast high-throughput screening (HTS) dataset have been linked to cleft palate based on data from ToxRefDB (rat or rabbit prenatal developmental toxicity studies) or from literature reports. These compounds are structurally diverse and thus likely to perturb prenatal development in mechanistically diverse ways. Integration of the HTS in vitro profiling data with information from chemotype profiling and automated literature survey provides a generalizable approach for adverse outcome pathway (AOP) elucidation. We generated a heatmap by clustering the 65 chemicals using as attributes 204 ToxCast Gene Scores and 233 chemical structural elements (chemotypes). Hierarchical relationships in the heatmap revealed several cohesive bioactivity-chemotype clusters. For example, the conazoles, retinoids, and phthalates formed clusters, as did the chemicals that hit GPCRs, angiogenic targets, and neuro-active targets. Identification of cohesive clusters enables focused literature mining for cellular and tissue effects linked to the ToxCast targets, and extension and enhancement of AOPs for cleft palate.