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Development of a Curated, Cross-Species Androgen Receptor Database
Citation:
Vliet, S., K. Markey, S. Lynn, AND C. LaLone. Development of a Curated, Cross-Species Androgen Receptor Database. SETAC, Pittsburgh, PA, November 13 - 17, 2022. https://doi.org/10.23645/epacomptox.21401595
Impact/Purpose:
It is the mission of the US Environmental Protection Agency (US EPA) to protect human and environmental health. One important part of protecting the environment is identifying chemicals that may be harmful to humans and animals exposed to them. This can be challenging because chemical testing is expensive and there are many chemicals that have not been tested and many different diverse species to protect. One way to get around this challenge and figure out how chemicals will affect different species is to look at data from studies that have already been conducted. This project uses computer-based methods to gather, review, and assess toxicity data published in the literature focused on the chemical target, androgen receptor. Data from relevant studies is then pulled out of publications and organized into a database. This research and database will help provide data for scientists to assess the effects of chemicals across species and will be a resource for future work.
Description:
The US Environmental Protection Agency (US EPA) is tasked with assessing chemicals for their potential to adversely impact human and environmental health. This often involves generating toxicity data for model organisms and extrapolating effects to species of concern. For ecological assessments, extrapolation to thousands of diverse organisms is necessary since testing within each species is simply not feasible. Further, limited resources and global efforts to reduce animal use make it challenging to meet demands for chemical testing. One potential solution is to utilize data already present in toxicological literature. This project develops a curated, cross-species database on the androgen receptor (AR) using an artificial intelligence-assisted systematic literature review to categorize in vitro and in vivo AR data of ecotoxicological relevance. To identify applicable literature, searches were conducted in both PubMed and Web of Science using query expansion technologies. Using web-based software to create evaluation templates, reviewers screened 3,216 in vitro and 1775 in vivo articles. Articles were initially screened by title and abstract for relevance followed by a full-text screening, which ensured certain criteria for data extraction were met and studies with critical deficiencies were excluded. Articles with relevant, high-quality data underwent data extraction for basic study design and effect information. At each screening stage, discrepancy analyses were conducted to identify disagreements between model and human reviewer responses. This process was assisted by machine learning models trained to identify potential disagreements. Following completion of the systematic review, 33 in vitro and 245 in vivo articles underwent complete data extraction, including articles containing data for 54 chemicals designated as AR pathway reference chemicals. Across in vitro articles, most extracted toxicity data were for fish species (25) with fewer articles for other non-mammalian taxa (5 avian, 2 amphibians, and 1 reptile). Similarly, the in vivo articles contained more fish data (196 articles) than for other taxa (20 avian, 29 amphibians, and 1 reptile). This database provides a scientific resource for a myriad of purposes including the validation of new testing methods and assessing the concordance of mammalian-based AR results with other species and assay platforms. The views expressed in this abstract do not necessarily reflect the policies of the US EPA.
URLs/Downloads:
DOI: Development of a Curated, Cross-Species Androgen Receptor Database
SETACNA 2022 POSTER-SVLIET_DRAFT2-STICS.PDF (PDF, NA pp, 3935.691 KB, about PDF)