The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is a premier public resource for literature-based, manually curated associations between chemicals, gene products, phenotypes, diseases, and environmental exposures. In this biennial update, we present our new chemical-phenotype module that codes chemical-induced effects on phenotypes, curated using controlled vocabularies for chemicals, phenotypes, taxa, and anatomical descriptors; this module provides unique opportunities to explore cellular and system-level phenotypes of the pre-disease state and allows users to construct predictive adverse outcome pathways (linking chemical-gene molecular initiating events with phenotypic key events, diseases, and population-level health outcomes). We also report a 46% increase in CTD manually curated content, which when integrated with other datasets yields more than 38 million toxicogenomic relationships. We describe new querying and display features for our enhanced chemical-exposure science module, providing greater scope of content and utility. As well, we discuss an updated MEDIC disease vocabulary with over 1700 new terms and accession identifiers. To accommodate these increases in data content and functionality, CTD has upgraded its computational infrastructure. These updates continue to improve CTD and help inform new testable hypotheses about the etiology and mechanisms underlying environmentally influenced diseases.

The public Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is an innovative digital ecosystem that relates toxicological information for chemicals, genes, phenotypes, diseases, and exposures to advance understanding about human health. Literature-based, manually curated interactions are integrated to create a knowledgebase that harmonizes cross-species heterogeneous data for chemical exposures and their biological repercussions. In this biennial update, we report a 20% increase in CTD curated content and now provide 45 million toxicogenomic relationships for over 16 300 chemicals, 51 300 genes, 5500 phenotypes, 7200 diseases and 163 000 exposure events, from 600 comparative species. Furthermore, we increase the functionality of chemical–phenotype content with new data-tabs on CTD Disease pages (to help fill in knowledge gaps for environmental health) and new phenotype search parameters (for Batch Query and Venn analysis tools). As well, we introduce new CTD Anatomy pages that allow users to uniquely explore and analyze chemical–phenotype interactions from an anatomical perspective. Finally, we have enhanced CTD Chemical pages with new literature-based chemical synonyms (to improve querying) and added 1600 amino acid-based compounds (to increase chemical landscape). Together, these updates continue to augment CTD as a powerful resource for generating testable hypotheses about the etiologies and molecular mechanisms underlying environmentally influenced diseases.

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) provides information about interactions between chemicals and gene products, and their relationships to diseases. Core CTD content (chemical-gene, chemical-disease and gene-disease interactions manually curated from the literature) are integrated with each other as well as with select external datasets to generate expanded networks and predict novel associations. Today, core CTD includes more than 30.5 million toxicogenomic connections relating chemicals/drugs, genes/proteins, diseases, taxa, Gene Ontology (GO) annotations, pathways, and gene interaction modules. In this update, we report a 33% increase in our core data content since 2015, describe our new exposure module (that harmonizes exposure science information with core toxicogenomic data) and introduce a novel dataset of GO-disease inferences (that identify common molecular underpinnings for seemingly unrelated pathologies). These advancements centralize and contextualize real-world chemical exposures with molecular pathways to help scientists generate testable hypotheses in an effort to understand the etiology and mechanisms underlying environmentally influenced diseases.

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) harmonizes cross-species heterogeneous data for chemical exposures and their biological repercussions by manually curating and interrelating chemical, gene, phenotype, anatomy, disease, taxa, and exposure content from the published literature. This curated information is integrated to generate inferences, providing potential molecular mediators to develop testable hypotheses and fill in knowledge gaps for environmental health. This dual nature, acting as both a knowledgebase and a discoverybase, makes CTD a unique resource for the scientific community. Here, we report a 20% increase in overall CTD content for 17 100 chemicals, 54 300 genes, 6100 phenotypes, 7270 diseases and 202 000 exposure statements. We also present CTD Tetramers, a novel tool that computationally generates four-unit information blocks connecting a chemical, gene, phenotype, and disease to construct potential molecular mechanistic pathways. Finally, we integrate terms for human biological media used in the CTD Exposure module to corresponding CTD Anatomy pages, allowing users to survey the chemical profiles for any tissue-of-interest and see how these environmental biomarkers are related to phenotypes for any anatomical site. These, and other webpage visual enhancements, continue to promote CTD as a practical, user-friendly, and innovative resource for finding information and generating testable hypotheses about environmental health.

Background:Exposure science studies the interactions and outcomes between environmental stressors and human or ecological receptors. To augment its role in understanding human health and the exposome, we aimed to centralize and integrate exposure science data into the broader biological framework of the Comparative Toxicogenomics Database (CTD), a public resource that promotes understanding of environmental chemicals and their effects on human health.Objectives:We integrated exposure data within the CTD to provide a centralized, freely available resource that facilitates identification of connections between real-world exposures, chemicals, genes/proteins, diseases, biological processes, and molecular pathways.Methods:We developed a manual curation paradigm that captures exposure data from the scientific literature using controlled vocabularies and free text within the context of four primary exposure concepts: stressor, receptor, exposure event, and exposure outcome. Using data from the Agricultural Health Study, we have illustrated the benefits of both centralization and integration of exposure information with CTD core data.Results:We have described our curation process, demonstrated how exposure data can be accessed and analyzed in the CTD, and shown how this integration provides a broad biological context for exposure data to promote mechanistic understanding of environmental influences on human health.Conclusions:Curation and integration of exposure data within the CTD provides researchers with new opportunities to correlate exposures with human health outcomes, to identify underlying potential molecular mechanisms, and to improve understanding about the exposome.Citation:Grondin CJ, Davis AP, Wiegers TC, King BL, Wiegers JA, Reif DM, Hoppin JA, Mattingly CJ. 2016. Advancing exposure science through chemical data curation and integration in the Comparative Toxicogenomics Database. Environ Health Perspect 124:1592–1599; http://dx.doi.org/10.1289/EHP174