MEDIC: a practical disease vocabulary used at the Comparative Toxicogenomics Database

Abstract

The Comparative Toxicogenomics Database (CTD) is a public resource that promotes understanding about the effects of environmental chemicals on human health. CTD biocurators manually curate a triad of chemical-gene, chemical-disease and gene-disease relationships from the scientific literature. The CTD curation paradigm uses controlled vocabularies for chemicals, genes and diseases. To curate disease information, CTD first had to identify a source of controlled terms. Two resources seemed to be good candidates: the Online Mendelian Inheritance in Man (OMIM) and the 'Diseases' branch of the National Library of Medicine's Medical Subject Headers (MeSH). To maximize the advantages of both, CTD biocurators undertook a novel initiative to map the flat list of OMIM disease terms into the hierarchical nature of the MeSH vocabulary. The result is CTD's 'merged disease vocabulary' (MEDIC), a unique resource that integrates OMIM terms, synonyms and identifiers with MeSH terms, synonyms, definitions, identifiers and hierarchical relationships. MEDIC is both a deep and broad vocabulary, composed of 9700 unique diseases described by more than 67 000 terms (including synonyms). It is freely available to download in various formats from CTD. While neither a true ontology nor a perfect solution, this vocabulary has nonetheless proved to be extremely successful and practical for our biocurators in generating over 2.5 million disease-associated toxicogenomic relationships in CTD. Other external databases have also begun to adopt MEDIC for their disease vocabulary. Here, we describe the construction, implementation, maintenance and use of MEDIC to raise awareness of this resource and to offer it as a putative scaffold in the formal construction of an official disease ontology. DATABASE URL: http://ctd.mdibl.org/voc.go?type=disease.

Figure 1.

MEDIC is freely available from CTD. To obtain the most recent version of MEDIC, use the ‘Downloads’ menu tab. The vocabulary can be downloaded in various formats including CSV, TSV (red circle and inset), XML and OBO. We encourage other databases that use MEDIC to provide a direct link from their disease page to CTD’s equivalent disease page to promote interoperability between databases.

Figure 2.

Components of MEDIC. As of October 2011, MEDIC contained 9706 unique disease primary terms and 58 074 synonyms. It includes 6197 MeSH primary terms, 1845 OMIM primary terms (as leaf nodes) and 1664 MeSH primary terms (that have 2593 OMIM primary terms merged to them).

Figure 3.

Curating to MEDIC. CTD biocurators use MEDIC as their disease vocabulary when curating chemical–disease and gene–disease data. The ‘Diseases’ tab (orange) on CTD's chemical page for resveratrol displays the curated relationships between the chemical and over 50 diseases (red box, partial screenshot). The green M icon indicates resveratrol is a marker for or plays a molecular role in the disease; the purple T icon indicates the chemical is a real or putative therapeutic for the disease. Every disease term is hyperlinked to its own disease page, allowing users to seamlessly explore chemical-gene-disease networks.

Figure 4.

CTD's disease page for type 2 diabetes. (a) The disease page is anchored to the MeSH term ‘Diabetes Mellitus, Type 2’ (MESH: D003924). Equivalent OMIM diseases are merged to the MeSH page in MEDIC. All accession IDs are hyperlinked to their respective databases. (b) Merged OMIM terms and synonyms are easily recognizable by their capitalization. (c) OMIM terms can be leaf nodes beneath MeSH terms, and users can see the hierarchy in which the terms fall by following the Paths. (d) CTD-curated data for type 2 diabetes can be seen by clicking on the appropriate data-tabs.

Figure 5.

Navigating MEDIC and its curated data. A bird's eye view of a section of MEDIC provides users with the ability to navigate and explore disease terms, relationships, and their associated CTD data. The disease ‘DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS’ (OMIM:610549) is a leaf of ‘Diabetes Mellitus, Type 2’ (MESH:D003924) and ‘Acanthosis Nigricans’ (MESH:D000052). Chemicals and genes annotated to each MEDIC term are cumulated as the user navigates up to more broad concepts.

Figure 6.

DiseaseComps use MEDIC. The DiseaseComps tab (orange) ranks diseases similar to ‘DRAVET SYNDROME’ based upon shared genes. DiseaseComps, which employs MEDIC as its disease vocabulary, ranks a mixture of both MeSH and OMIM terms (recognizable by its capitalization) based upon their similarity index. ‘DRAVET SYNDROME’ is discovered to share genes with epilepsy, migraines and hepatic encephalopathy.