Comparative Toxicogenomics Database (CTD)

Category Cross-Omics>Knowledge Bases/Databases/Tools and Genomics>Genetic Data Analysis/Tools

Abstract The Comparative Toxicogenomics Database (CTD) is a knowledge base and discovery tool for chemical-gene-disease networks. It 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 (GO), 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 knowledge base (by reporting data) and a discovery tool (by generating novel inferences).

CTD provides over 178,000 interactions between 4,980 chemicals and 16,182 genes and proteins in 298 species as well as more than 5,600 chemical-disease, and 8,900 gene/protein-disease relationships.

By integrating curated data among chemicals, genes and diseases, ‘novel transitive relationships’ can be inferred.

CTD provides over 629,000 inferred gene-disease relationships and 172,000 inferred chemical-disease relationships that may be used to develop novel hypotheses about chemical-gene-disease networks.

This wealth of chemical-gene-disease information also yields testable hypotheses for understanding the effects of environmental chemicals on human health.

CTD Primary Data Categories --

1) 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, pathways and references) using the chemical browser. You can also use it to formulate gene, interaction and reference queries.

2) 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 (GO) 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 (GO) annotation.

3) Chemical-Gene/Protein Interactions - To improve understanding about the mechanisms of chemical actions, the manufacturers 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 controlled interaction 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.

4) Diseases - CTD diseases consist of ‘genetic disorders’ from the Online Mendelian Inheritance in Man (OMIM) database at the National Center for Biotechnology Information (NCBI) and the disease subset of the Medical Subject Headings (MeSH®), resources available through the U.S. National Library of Medicine.

CTD curators mapped OMIM diseases to terms within the hierarchical MeSH disease vocabulary to expand disease representation in CTD. This combined disease vocabulary is used to curate gene-disease and chemical-disease relationships. You can browse diseases and use them to formulate gene and reference queries.

5) Gene-Disease Relationships - CTD contains direct and inferred gene-disease relationships. Direct gene-disease relationships are curated from the published literature by CTD curators, or are derived from the OMIM database using the ‘mim2gene file’ from the NCBI Gene database.

Inferred relationships 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 direct relationship with disease B). Direct and inferred relationships are identified, and help users develop hypotheses about mechanisms underlying environmental diseases.

6) Chemical-Disease Relationships - CTD contains direct and inferred chemical-disease relationships. Direct chemical-disease relationships are curated from the published literature by CTD curators.

Inferred relationships 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 direct relationship with disease B). Direct and inferred relationships are identified, and help users develop hypotheses about mechanisms underlying ‘environmental diseases’.

7) References - CTD contains references 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, the manufacturers are curating chemical- gene interactions from these references.

8) Organisms – CTD’s hierarchical organism vocabulary consists of the Eumetazoa (vertebrates and invertebrates) component of the Taxonomy Database from 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.

9) Gene Ontology (GO) - GO annotations are integrated with gene data in CTD. You can ‘browse GO’ and use it to formulate gene and interaction queries.

10) Pathways - KEGG and REACTOME (see G6G Abstract Number 20267) pathway data is a collection of manually drawn pathway maps representing 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 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.

CTD Additional tools --

1) Batch Query - Download data associated with your list of chemicals, diseases or genes.

2) VennViewer - Compare associated data sets for up to three chemicals, diseases or genes. With this tool you can create a ‘Venn diagram’ to compare associated data sets for up to three chemicals, diseases or genes.

Venn diagrams or set diagrams are diagrams that show all hypothetically possible logical relations between a finite collection of sets (groups of things). Venn diagrams were conceived around 1880 by John Venn. They are used to teach elementary set theory, as well as illustrate simple set relationships in probability, logic, statistics, linguistics, and computer science.

3) MyGeneVenn - Compare your gene list to genes associated with up to two chemicals or diseases. With this tool you can create a Venn diagram to compare your gene list to genes associated with up to two chemicals or diseases.

System Requirements

Web-based.

Manufacturer

Manufacturer Web Site Comparative Toxicogenomics Database (CTD)

Price Contact manufacturer.

G6G Abstract Number 20542

G6G Manufacturer Number 104157