The long-range goal of the proposed project is to provide a centralized, freely available resource with comprehensive, well-annotated data and analysis tools that informs hypothesis development and interpretation of environmental health studies and promotes understanding about the etiologies of environmental diseases. Most human diseases involve interactions between genetic and environmental factors. The environment is implicated in many common conditions such as asthma, cancer, and diabetes;however, the etiology of these widespread diseases remains unclear. More than 85,000 chemicals are currently used in commerce, challenging elucidation about chemical mechanisms of action and prioritization of environmental research. Integration of critical data with novel analysis approaches is required to understand environment-disease associations and is essential for improving toxicity prediction, risk assessment, regulation and development of effective therapeutic interventions. We developed the freely available Comparative Toxicogenomics Database (CTD; to address this need. CTD provides manually curated data describing cross-species chemical-gene interactions and chemical- and gene-disease relationships from the peer-reviewed literature and integrates this information with select external data sets (e.g., molecular pathways) and novel analysis tools. In this application we propose to: 1) comprehensively curate chemical- gene-disease interactions and expand the scope of phenotype curation to include cellular and diverse organism effects that will enable users to: a) identify biomarkers of environmentally influenced diseases and b) infer potential human health consequences from toxicological studies in model organisms and in vitro studies;and 2) design and implement new tools to facilitate development, analysis and interpretation of novel hypotheses focused on chemical-gene-disease interaction networks. This proposed project will leverage our cutting-edge software development, curation expertise and well-established, flexible infrastructure to facilitate increased understanding of critical environmental health issues in direct alignment with emerging research priorities.

Public Health Relevance

This project is relevant to public health because it will support the only freely available curated resource dedicated to promoting understanding about the effects of the environment on human health. It will leverage past investments and the demonstrated value of the Comparative Toxicogenomics Database (CTD) to build data content and novel analysis tools for the research community that will facilitate development of new, testable hypotheses about chemical-gene-disease interaction networks and advance understanding about the causes of environmentally influenced diseases.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Study Section
Biodata Management and Analysis Study Section (BDMA)
Program Officer
Balshaw, David M
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Mount Desert Island Biological Lab
Salsbury Cove
United States
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Davis, Allan Peter; Wiegers, Thomas C; Wiegers, Jolene et al. (2018) Chemical-Induced Phenotypes at CTD Help Inform the Predisease State and Construct Adverse Outcome Pathways. Toxicol Sci 165:145-156
Grondin, Cynthia J; Davis, Allan Peter; Wiegers, Thomas C et al. (2018) Accessing an Expanded Exposure Science Module at the Comparative Toxicogenomics Database. Environ Health Perspect 126:014501
Davis, Allan Peter; Grondin, Cynthia J; Johnson, Robin J et al. (2018) The Comparative Toxicogenomics Database: update 2019. Nucleic Acids Res :
Planchart, Antonio; Green, Adrian; Hoyo, Cathrine et al. (2018) Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System Studies. Curr Environ Health Rep 5:110-124
Leung, Maxwell C K; Procter, Andrew C; Goldstone, Jared V et al. (2017) Applying evolutionary genetics to developmental toxicology and risk assessment. Reprod Toxicol 69:174-186
Davis, Allan Peter; Grondin, Cynthia J; Johnson, Robin J et al. (2017) The Comparative Toxicogenomics Database: update 2017. Nucleic Acids Res 45:D972-D978
Manrai, Arjun K; Cui, Yuxia; Bushel, Pierre R et al. (2017) Informatics and Data Analytics to Support Exposome-Based Discovery for Public Health. Annu Rev Public Health 38:279-294
Li, Jiao; Sun, Yueping; Johnson, Robin J et al. (2016) BioCreative V CDR task corpus: a resource for chemical disease relation extraction. Database (Oxford) 2016:
Mattingly, Carolyn J; Boyles, Rebecca; Lawler, Cindy P et al. (2016) Laying a Community-Based Foundation for Data-Driven Semantic Standards in Environmental Health Sciences. Environ Health Perspect 124:1136-40
Grondin, Cynthia J; Davis, Allan Peter; Wiegers, Thomas C et al. (2016) Advancing Exposure Science through Chemical Data Curation and Integration in the Comparative Toxicogenomics Database. Environ Health Perspect 124:1592-1599

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