Exposure Science in The Comparative Toxicogenomics Database: Linking Chemical Stressors to Outcomes via an Exposure Ontology

摘要

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org) is a freely available resource that provides manually curated information on chemical, gene, phenotype, and disease relationships to further our understanding of environmental exposures on human health. Four primary modules are independently curated into CTD, including chemical-gene interactions, chemical-disease and gene-disease associations, chemically-induced phenotype relationships, and environmental exposure data. The latter includes exposure measurements and effects on human populations (receptors). Approximately 50 characteristics of exposure studies are curated including nformation about exposure sources, population demographics, measured media and levels, locations and outcomes using standardized terms from the exposure ontology (ExO) and additional controlled vocabularies. Integration of these data into CTD provides a centralized, searchable repository of exposure data that facilitates meta-analyses and informs study design by allowing comparisons among experimental parameters. To date, over 800 unique chemical stressors and 500 disease/phenotype outcomes have been described (from over 1500 articles), and these data are linked to over 1.7 million chemical-gene-disease interactions and 80,000 chemical-phenotype interactions in CTD. Analysis tools in CTD reveal direct and inferred relationships among the data, and help generate, interpret and refine hypotheses relating to chemically-influenced diseases. CTD's centralization of exposure science data, integration with chemical-gene, disease and phenotype modules, and additional analysis tools provide a unique resource to advance our understanding of the molecular mechanisms of action of environmental exposures and their effects on human health.