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The ToxCast Pathway Database for Identifying Toxicity Signatures and Potential Modes of Action from Chemical Screening Data
Citation:
MORTENSEN, H. M., D. J. DIX, K. A. HOUCK, R. J. KAVLOCK, I. A. SHAH, AND R. JUDSON. The ToxCast Pathway Database for Identifying Toxicity Signatures and Potential Modes of Action from Chemical Screening Data. Presented at Society of Toxicology Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
The ToxCast Pathway Database (ToxPath) will be used to organize this extensive dataset, to perform network analyses, and to visualize putative modes of action that are activated by particular chemicals. Network analysis will facilitate the inference of predictive toxicological signatures by providing a visually intuitive representation of quantitative chemical effects across multiple levels of biological organization, including relationships to in vivo toxicity endpoints. This will define relationships between chemicals and disease states in whole animals, and potential disease states in humans. Initial analysis of ToxCast assays based on Entrez GeneID identified 113 human and 39 rat pathways within Ingenuity Pathway Analysis that contained at least one ToxCast assay target. ToxPath will contribute to the larger goals of toxicogenomics by clarifying the role of gene-environment interactions in disease states
Description:
The U.S. Environmental Protection Agency (EPA), through its ToxCast program, is developing predictive toxicity approaches that will use in vitro high-throughput screening (HTS), high-content screening (HCS) and toxicogenomic data to predict in vivo toxicity phenotypes. There are two major goals of this effort: 1) to produce toxicity signatures that can be applied to a large number of environmental chemicals for screening and prioritization; 2) to provide a more mechanistic understanding of chemical toxicity pathways. Towards these goals, we are developing a database and associated tools that organize the ToxCast data generated from over 600 different assays into pathways (e.g. toxicological, biochemical, metabolic, cellular), and then identifying pathway networks from which modes of action can be inferred. ToxCast in vitro assay data probe many biological domains and span multiple levels of biological organization.