The Comparative Toxicogenomics Database: update 2011

Abstract

The Comparative Toxicogenomics Database (CTD) is a public resource that promotes understanding about the interaction of environmental chemicals with gene products, and their effects on human health. Biocurators at CTD manually curate a triad of chemical-gene, chemical-disease and gene-disease relationships from the literature. These core data are then integrated to construct chemical-gene-disease networks and to predict many novel relationships using different types of associated data. Since 2009, we dramatically increased the content of CTD to 1.4 million chemical-gene-disease data points and added many features, statistical analyses and analytical tools, including GeneComps and ChemComps (to find comparable genes and chemicals that share toxicogenomic profiles), enriched Gene Ontology terms associated with chemicals, statistically ranked chemical-disease inferences, Venn diagram tools to discover overlapping and unique attributes of any set of chemicals, genes or disease, and enhanced gene pathway data content, among other features. Together, this wealth of expanded chemical-gene-disease data continues to help users generate testable hypotheses about the molecular mechanisms of environmental diseases. CTD is freely available at http://ctd.mdibl.org.

Figure 1.

CTD’s unique use of enriched GO terms for chemicals. On the highlighted ‘GO’ data tab (red circle) for a chemical, users will find enriched GO terms. Here, the insecticide diazinon has curated interactions with 215 genes. The GO annotations for these genes are statistically enriched and only the significant GO terms (P-value less than 0.01, expressed as an enrichment score) are shown for the chemical (inset). Cluster and genome frequency calculations are also provided. Users can sort the table by the column headers: Ontology, GO level, GO term, Enrichment score and Annotated genes. All CTD pages can be downloaded by using the ‘Save to file’ feature at the bottom of every page.

Figure 2.

Network scores help rank chemical–disease inferences. On the highlighted ‘Disease’ data tab (red circle) for the chemical tetrachlorodibenzodioxin (TCDD), users find both direct and inferred disease associations. Inferred chemical–disease relationships are enhanced with inference network scores, allowing predicted relationships to be sorted and prioritized. In this partial screenshot, the highest inference score (408.24) associates TCDD with prostrate cancer based upon 65 genes that interact with TCDD and independently have a direct relationship with the disease (inset and red box). For more information about inference scores, click the ‘Help’ popup box (question mark link) in the upper-right corner of the text section.

Figure 3.

CTD provides new analytical tools. (a) VennViewer allows users to create online Venn diagrams to compare associated datasets for any three chemicals, genes or disease. Here, the three chemicals tretinoin, sodium arsenite and curcumin are analyzed to find common curated diseases, including four diseases shared by all three chemicals. (b) MyGeneVenn lets users upload gene lists of interest to find supporting data or to determine which genes from their set have an association with specified chemicals or diseases in CTD. Shown here, from a user’s input of 75 genes (‘My Data’), 46 genes are also found to interact with resveratrol and genistein, seven interact with resveratrol only and nine interact with genistein only.