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Leveraging ToxCast (TM) Annotations for Interpretation of In Vitro Bioactivity Data
Citation:
Feshuk, M. AND C. Elonen. Leveraging ToxCast (TM) Annotations for Interpretation of In Vitro Bioactivity Data. SOT, Salt Lake City, UT, March 10 - 14, 2024. https://doi.org/10.23645/epacomptox.25395412
Impact/Purpose:
The ToxCast data pipeline (tcpl) is an open-source R package that stores, manages, curve-fits, and visualizes ToxCast data as well as populating the linked MySQL Database, InvitroDB. These Tcpl and InvitroDB enhancements will support the continued utility of ToxCast in vitro screening results as a resource for bioactivity data in myriad toxicology applications.
Description:
Building confidence in new approach methodologies (NAMs) for prioritization and hazard characterization requires accessible and easily interpretable bioactivity data. The U.S. Environmental Protection Agency (EPA) Toxicity Forecaster (ToxCast) continues to provide one of the largest and most impactful public repositories of targeted in vitro NAMs for toxicology. To process, model, and visualize concentration-response screening data as well as populate a linked MySQL Database,¿invitrodb, the¿ToxCast¿pipeline R package, tcpl, enables flexible data processing and analysis. Assay annotations are essential for proper interpretation of screening results and facilitate higher level analyses, such as incorporation of hit calls and estimates of potency and efficacy into toxicity prediction models. The annotation structure follows principles outlined by the Bioassay Ontology¿(BAO; http://bioassayontology.org/) efforts to describe the heterogenous ToxCast assay suite by technology¿, format¿, objective, target, and analysis. The assay, assay component, and assay component endpoint tables store these manually curated and expertly reviewed experimental and biological details. Auxiliary annotation tables capture additional information, such as the most relevant National Center for Biotechnology Information (NCBI) gene identifier, reagents or experimental conditions, and publications describing results. Organisation for Economic Co-operation and Development (OECD) guidance document (GD) 211 suggests components of comprehensive assay documentation describing non-guideline in vitro test methods and their interpretation. The intent of GD 211 is to harmonize non-guideline, in vitro method descriptions to allow assessment of the relevance of the test method for biological responses of interest and the quality of the data produced. Major software and database enhancements to tcpl and invitrodb into a bidirectional curve fitting paradigm warrant an update to all existing assay descriptions, with additional curation ongoing and efforts to enhance documentation for GD 211. This curation work, along with the standardized and documented data processing procedures with tcpl, make invitrodb an important publicly available data resource that follows and supports the Findable, Accessible, Interoperable, and Reusable (FAIR) data principles needed for data interoperability in workflows that utilize bioactivity data. This session will explore the ToxCast annotation structure and curation process, then demonstrate an example analysis of bridging ontologies between ToxCast and the Toxicity Reference Database (ToxRefDB) for research applications. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: Leveraging ToxCast (TM) Annotations for Interpretation of In Vitro Bioactivity Data
PRESENTATION.PDF (PDF, NA pp, 2422.525 KB, about PDF)