You are here:
Identifying candidate reference chemicals for in vitro testing of the retinoid pathway from public data and literature mining
Citation:
Baker, Nancy C., J. Pierro, L. Taylor, AND T. Knudsen. Identifying candidate reference chemicals for in vitro testing of the retinoid pathway from public data and literature mining. Society of Toxicology 61st Annual Meeting and ToxExpo 2022, San Diego, California, March 27 - 31, 2022. https://doi.org/10.23645/epacomptox.19576558
Impact/Purpose:
Poster presented to the Society of Toxicology 61st Annual Meeting and ToxExpo March 2022.
Description:
Using in vitro bioactivity of chemicals to predict in vivo toxicity is an important component of animal-free toxicity testing. Sets of reference chemicals and data measuring their activity against targets of interest are essential both to validate and establish confidence in in vitro assays. The retinoic acid (RA) signaling pathway is especially important in developmental processes and toxic exposure. Employing data extraction methods and advanced literature mining tools, we assembled a set of candidate reference chemicals for activity on ten protein family targets in the retinoid system (serum retinol binding protein, stimulated by retinoic acid 6, cellular retinol binding protein, cellular retinoic acid binding protein, retinoic acid 4-hydroxylase, retinol dehydrogenase, retinal dehydrogenase, retinoic acid receptors alpha, beta and gamma (RARA, RARB, RARG)). The collection was assembled from Protein Data Bank, ChEMBL, ToxCast/Tox21, and the biomedical literature in PubMed. The process produced approximately 220 putative reference chemicals. When this set was inserted into the Abstract Sifter literature tool and PubMed searches were performed, around 137 (approximately 75%) of the chemicals showed literature connections to developmental toxicity. When the queries are structured to focus on one developmental adverse outcome associated with retinoid disruption – limb defects – we find approximately 55 chemicals have some supporting literature. These methods produced a strong pool of candidate reference chemicals. The integration of the chemical set into an Abstract Sifter literature tool facilitates the investigation of the chemicals’ known downstream effects and provides connections via hyperlinks to the EPA Chemicals Dashboard with its rich chemical information encompassing in vitro profiling, in vivo data and computational predictions. This abstract does not necessarily represent U.S. EPA policy.
URLs/Downloads:
DOI: Identifying candidate reference chemicals for in vitro testing of the retinoid pathway from public data and literature mining
BAKER_SOT_2022_RETINOID_TOPRINT.PDF (PDF, NA pp, 574.011 KB, about PDF)