Comparative Toxicogenomics Database: a knowledgebase and discovery tool for chemical-gene-disease networks

Abstract

The Comparative Toxicogenomics Database (CTD) is a curated database that promotes understanding about the effects of environmental chemicals on human health. Biocurators at CTD manually curate chemical–gene interactions, chemical–disease relationships and gene–disease relationships from the literature. This strategy allows data to be integrated to construct chemical–gene–disease networks. CTD is unique in numerous respects: curation focuses on environmental chemicals; interactions are manually curated; interactions are constructed using controlled vocabularies and hierarchies; additional gene attributes (such as Gene Ontology, taxonomy and KEGG pathways) are integrated; data can be viewed from the perspective of a chemical, gene or disease; results and batch queries can be downloaded and saved; and most importantly, CTD acts as both a knowledgebase (by reporting data) and a discovery tool (by generating novel inferences). Over 116 000 interactions between 3900 chemicals and 13 300 genes have been curated from 270 species, and 5900 gene–disease and 2500 chemical–disease direct relationships have been captured. By integrating these data, 350 000 gene–disease relationships and 77 000 chemical–disease relationships can be inferred. This wealth of chemical–gene–disease information yields testable hypotheses for understanding the effects of environmental chemicals on human health. CTD is freely available at http://ctd.mdibl.org.

Combining Drug and Gene Similarity Measures for Drug-Target Elucidation

“…For an additional validation, we utilized information on drug-related pathways of KEGG (Kanehisa et al, 2010) and REACTOME (Matthews et al, 2009) databases, as cataloged in the Comparative Toxicogenomics Database (CTD) (Davis et al, 2009). Out of the 315 drugs used in this paper, 217 drugs are associated with known pathways in CTD.…”

Exploiting Negative Sample Selection for Prioritizing Candidate Disease Genes

“…Gene-disease benchmark associations regard 708 selected MeSH disease terms, and are downloaded from the Comparative Toxicogenomics Database (CTD) [31]. Such diseases posses 5 to 200 causative genes.…”

Mapping the genome of Plasmodium falciparum on the drug-like chemical space reveals novel anti-malarial targets and potential drug leads

“…Structural similarity was assessed by the Tanimoto coefficient using a cut-off value of 0.85. Information on chemical-protein interactions was extracted from ChemProt 18 a repository of 700 000 unique chemicals and 30 578 proteins, assembled from both proprietary and freely available databases, including ChEMBL, 31 BindingDB, 32 PDSP Ki Database, 33 DrugBank, 34 PharmGKB, 35 WOMBAT, 36 WOMBAT-PK, 36 PubChem bioassay, 37 CTD 27 and STITCH. 38 The protein sequences were retrieved from Batch Entrez (http://www.ncbi.nlm.nih.gov/sites/batchentrez) and were blasted against the proteome of P. falciparum's (NCBI Genome Project ID 148) with cut-off e-value of 10…”

“…We further studied potentially toxic off-target interactions with human proteins and the 2512 polyactive GSK compounds, extracting information from the Comparative Toxicogenomics Database, 27 one of the databases within ChemProt, where drugs and environmental compounds are associated with toxicologically important proteins. CDK has information for only five GSK compounds that have been previously associated in the literature with adverse and toxic effects.…”