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;http://ctd.mdibl.org) 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES014065-08
Application #
8477188
Study Section
Biodata Management and Analysis Study Section (BDMA)
Program Officer
Balshaw, David M
Project Start
2005-08-01
Project End
2016-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
8
Fiscal Year
2013
Total Cost
$506,566
Indirect Cost
$166,589
Name
Mount Desert Island Biological Lab
Department
Type
DUNS #
077470003
City
Salsbury Cove
State
ME
Country
United States
Zip Code
04672
Davis, Allan Peter; Wiegers, Thomas C; Roberts, Phoebe M et al. (2013) A CTD-Pfizer collaboration: manual curation of 88,000 scientific articles text mined for drug-disease and drug-phenotype interactions. Database (Oxford) 2013:bat080
Davis, Allan Peter; Wiegers, Thomas C; Johnson, Robin J et al. (2013) Text mining effectively scores and ranks the literature for improving chemical-gene-disease curation at the comparative toxicogenomics database. PLoS One 8:e58201
Davis, Allan Peter; Murphy, Cynthia Grondin; Johnson, Robin et al. (2013) The Comparative Toxicogenomics Database: update 2013. Nucleic Acids Res 41:D1104-14
Cheng, Keith C; Hinton, David E; Mattingly, Carolyn J et al. (2012) Aquatic models, genomics and chemical risk management. Comp Biochem Physiol C Toxicol Pharmacol 155:169-73
Davis, Allan Peter; Wiegers, Thomas C; Rosenstein, Michael C et al. (2012) MEDIC: a practical disease vocabulary used at the Comparative Toxicogenomics Database. Database (Oxford) 2012:bar065
Bello, Susan M; Richardson, Joel E; Davis, Allan P et al. (2012) Disease model curation improvements at Mouse Genome Informatics. Database (Oxford) 2012:bar063
Hirschman, Lynette; Burns, Gully A P C; Krallinger, Martin et al. (2012) Text mining for the biocuration workflow. Database (Oxford) 2012:bas020
Davis, Allan Peter; Wiegers, Thomas C; Rosenstein, Michael C et al. (2011) The curation paradigm and application tool used for manual curation of the scientific literature at the Comparative Toxicogenomics Database. Database (Oxford) 2011:bar034
Davis, Allan Peter; King, Benjamin L; Mockus, Susan et al. (2011) The Comparative Toxicogenomics Database: update 2011. Nucleic Acids Res 39:D1067-72
Davis, Allan Peter; Murphy, Cynthia G; Saraceni-Richards, Cynthia A et al. (2009) Comparative Toxicogenomics Database: a knowledgebase and discovery tool for chemical-gene-disease networks. Nucleic Acids Res 37:D786-92

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