The comparative toxicogenomics database: a cross-species resource for building chemical-gene interaction networks

Abstract

Chemicals in the environment play a critical role in the etiology of many human diseases. Despite their prevalence, the molecular mechanisms of action and the effects of chemicals on susceptibility to disease are not well understood. To promote understanding of these mechanisms, the Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org/) presents scientifically reviewed and curated information on chemicals, relevant genes and proteins, and their interactions in vertebrates and invertebrates. CTD integrates sequence, reference, species, microarray, and general toxicology information to provide a unique centralized resource for toxicogenomic research. The database also provides visualization capabilities that enable cross-species comparisons of gene and protein sequences. These comparisons will facilitate understanding of structure-function correlations and the genetic basis of susceptibility. Manual curation and integration of cross-species chemical-gene and chemical-protein interactions from the literature are now underway. These data will provide information for building complex interaction networks. New CTD features include (1) cross-species gene, rather than sequence, query and visualization capabilities; (2) integrated cross-links to microarray data from chemicals, genes, and sequences in CTD; (3) a reference set related to chemical-gene and protein interactions identified by an information retrieval system; and (4) a "Chemicals in the News" initiative that provides links from CTD chemicals to environmental health articles from the popular press. Here we describe these new features and our novel cross-species curation of chemical-gene and chemical-protein interactions.

Figure 1

High Level View of the Primary Data Types in CTD.

Figure 2

Overview of CTD information retrieval process. White objects represent manual or automated processes. Dark grey objects represent physical objects (files or databases).

Figure 3

Sample CTD Chemical Detail Page. The CTD chemical detail page provides a description, synonyms and CAS name, a chemical structure drawing, links to supplemental data in other databases such as microarray data, and access to associated genes and references in CTD.

Figure 4

Chemical-Gene Interaction Network Schematic. Cross-species interactions between chemicals and genes and proteins are curated manually from the literature for CTD. These data will be important for building complex interaction networks. This high-level schematic represents specific interactions that have been curated between lipopolysaccharides (LPS) and 286 genes and proteins, as well as integration with other relevant data such as associated diseases. A list of these genes and proteins are provided as supplementary data. Curated interaction data will be integrated with the CTD web interface in future releases. Square, unique genes and proteins (not a one:one ratio); circle, chemical; rounded rectangle, CTD interactions; shadowed rectangle, associated data (e.g., diseases associated with LPS); arrowed lines, activation; bullet lines, inhibition (e.g., LPS activates expression of 152 genes and inhibits activity of 4 proteins).