Giving insight into how chemicals affect our health.
Comparative Toxicogenomics Database

Contents

1. Overview
2. Support
3. Primary Data Categories
4. Footnotes

Top Overview

CTD advances understanding of the effects of environmental chemicals on human health.

The etiology of most chronic diseases involves interactions between environmental factors and genes that modulate important physiological processes.[1],[2] This assumption is supported by the many complex diseases caused by reversible behaviors or avoidable exposures, and by the relatively rare number of diseases attributed to single gene mutations.[2] Environmental factors are implicated in many common conditions such as asthma, cancer, diabetes, hypertension, immune deficiency disorders and Parkinson’s disease. The molecular mechanisms underlying these correlations, however, are not well understood.[3]

CTD includes curated data describing cross-species chemical–gene/protein interactions and chemical– and gene–disease associations to illuminate molecular mechanisms underlying variable susceptibility and environmentally influenced diseases. These data will also provide insights into complex chemical–gene and protein interaction networks.

Top Support

CTD is a community-supported public resource. It is being developed at the Mount Desert Island Biological Laboratory (MDIBL), with support from the National Institutes of Environmental Health Sciences (NIEHS) (ES014065) and the National Center for Research Resources (NCRR) (RR016463) of the National Institutes of Health (NIH). More…

Top Primary Data Categories

Chemicals

CTD integrates a chemical subset of the Medical Subject Headings (MeSH^®), the hierarchical vocabulary from the U.S. National Library of Medicine. You can view relationships among chemicals, obtain detailed information about them (including structure and toxicology data) and access related data (including genes, diseases, enriched GO terms, pathways and references) using the chemical browser. You can also use it to formulate gene, interaction and reference queries.

Genes

The cross-species gene vocabulary (symbols, names, and synonyms) in CTD is derived from the Gene database at the National Center for Biotechnology Information (NCBI), a division of the U.S. National Library of Medicine. CTD curators may add to this vocabulary as required (e.g., to represent a species-specific gene that is not curated in NCBI Gene). Chemical, chemical–gene interaction, disease, reference, Gene Ontology and organism data are also provided for genes. You can search for genes by chemical name/symbol/accession ID, chemical–gene interaction type, gene symbol/name, disease, organism or Gene Ontology annotation.

Chemical–Gene/Protein Interactions

To improve understanding about the mechanisms of chemical actions, we manually curate chemical–gene and protein interactions in vertebrates and invertebrates from the published literature. These interactions are both direct (e.g., “chemical binds to protein”) and indirect (e.g., “chemical results in increased phosphorylation of a protein” via intermediate events).

Interactions are curated using a hierarchical controlled interaction-type vocabulary that characterizes common physical, regulatory and biochemical interactions between chemicals and genes or proteins. This vocabulary comprises 70 terms including actions (e.g., “binds to”, “imports”), operators that describe the degree of a chemical's effect (e.g., “increases”), and qualifiers that specify the form of the gene or chemical involved in an interaction (e.g., “protein” or “chemical metabolite,” respectively).

You can search chemical–gene interactions directly on the chemical–gene interaction query form. You may also search them on the gene and reference query forms by using the “chemical–gene interaction types” field. Chemical–gene interactions are presented via gene, reference and chemical detail pages. References that have not yet been curated manually are presented in CTD with chemical–gene/protein associations that have been extracted by an automated information retrieval method. Performing gene or reference queries without the “chemical–gene interaction types” field, you will search both manually curated interactions and automated chemical–gene associations.

Diseases

CTD's “MEDIC” disease vocabulary is a modified subset of descriptors from the “Diseases” category of the the U.S. National Library of Medicine (NLM) Medical Subject Headings (MeSH^®), combined with genetic disorders from the Online Mendelian Inheritance in Man^® (OMIM^®) database. CTD curators mapped OMIM diseases to terms within the hierarchical MeSH disease vocabulary to expand our disease representation. This combined vocabulary is used to curate gene–disease and chemical–disease associations. You can browse diseases and use them to formulate gene and reference queries.

Gene–Disease Associations

CTD contains curated and inferred gene–disease associations. Curated gene–disease associations are extracted from the published literature by CTD curators, or are derived from the OMIM database using the mim2gene file from the NCBI Gene database. Inferred associations are established via CTD–curated chemical–gene interactions (e.g., gene A is associated with disease B because gene A has a curated interaction with chemical C, and chemical C has a curated association with disease B). Curated and inferred associations are identified, and help users develop hypotheses about mechanisms underlying environmental diseases.

Chemical–Disease Associations

CTD contains curated and inferred chemical–disease associations. Curated chemical–disease associations are extracted from the published literature by CTD curators. Inferred associations are established via CTD–curated chemical–gene interactions (e.g., chemical A is associated with disease B because chemical A has a curated interaction with gene C, and gene C has a curated association with disease B). Curated and inferred associations are identified, and help users develop hypotheses about mechanisms underlying environmental diseases.

References

CTD contains reference articles related to toxicologically significant vertebrate and invertebrate genes, diseases and associated chemicals. References were identified by information retrieval methods and comprise a subset of MEDLINE ^®/PubMed^®, a database of the U.S. National Library of Medicine. You can search for references by chemical, gene, organism taxon, disease, citation information and accession identifier. Using manual and automated methods, we are curating chemical–gene interactions from these references.

Organisms

CTD's hierarchical organism vocabulary consists of the Eumetazoa (vertebrates and invertebrates) branch of the Taxonomy Database from the National Center for Biotechnology Information (NCBI), a division of the U.S. National Library of Medicine. You can browse organisms and use them to formulate gene, interaction and reference queries.

Gene Ontology

Gene Ontology (GO) annotations are integrated with gene data in CTD. In addition, GO terms that are statistically enriched among genes/proteins that interact with a chemical are displayed for each chemical. You can browse GO and use it to formulate gene and interaction queries.

Pathways

KEGG and REACTOME pathway data is a collection of manually drawn pathway maps representing our knowledge on the molecular interaction and reaction networks. These data are integrated with chemicals, genes and diseases in CTD to provide insights into molecular networks that may be affected by chemicals, and possible mechanisms underlying environmental diseases. You can browse pathways, and use KEGG or REACTOME pathway names or IDs to formulate gene and interaction queries. Pathway information is provided on chemical, gene and disease detail pages.

Exposures

We are working to enhance the capacity to identify environment–disease connections by developing an Exposure Ontology that will be used to curate and integrate exposure data into CTD. More…

Top Footnotes

[1]

Schwartz DA, Freedman JH, Linney EA. Environmental genomics: a key to understanding biology, pathophysiology and disease. Hum Mol Genet. 2004 Oct 1;13 Spec No 2:R217-24. [PubMed:15358728]

[2]

Olden K, Wilson S. Environmental health and genomics: visions and implications. Nat Rev Genet. 2000 Nov;1(2):149-53. [PubMed:11253655]

[3]

Toscano WA, Oehlke KP. Systems biology: new approaches to old environmental health problems. Int J Environ Res Public Health. 2005 Apr;2(1):4-9. [PubMed:16705795]