Disease Ontology: improving and unifying disease annotations across species

Abstract

Model organisms are vital to uncovering the mechanisms of human disease and developing new therapeutic tools. Researchers collecting and integrating relevant model organism and/or human data often apply disparate terminologies (vocabularies and ontologies), making comparisons and inferences difficult. A unified disease ontology is required that connects data annotated using diverse disease terminologies, and in which the terminology relationships are continuously maintained. The Mouse Genome Database (MGD, http://www.informatics.jax.org), Rat Genome Database (RGD, http://rgd.mcw.edu) and Disease Ontology (DO, http://www.disease-ontology.org) projects are collaborating to augment DO, aligning and incorporating disease terms used by MGD and RGD, and improving DO as a tool for unifying disease annotations across species. Coordinated assessment of MGD's and RGD's disease term annotations identified new terms that enhance DO's representation of human diseases. Expansion of DO term content and cross-references to clinical vocabularies (e.g. OMIM, ORDO, MeSH) has enriched the DO's domain coverage and utility for annotating many types of data generated from experimental and clinical investigations. The extension of anatomy-based DO classification structure of disease improves accessibility of terms and facilitates application of DO for computational research. A consistent representation of disease associations across data types from cellular to whole organism, generated from clinical and model organism studies, will promote the integration, mining and comparative analysis of these data. The coordinated enrichment of the DO and adoption of DO by MGD and RGD demonstrates DO's usability across human data, MGD, RGD and the rest of the model organism database community.

Keywords: Disease models; Mouse; Ontologies; Rat.

Fig. 1.

Division of osteogenesis imperfecta (OI) terms in DO. Increasing the granularity of OI terms in DO (shown on the right) allows for refined relationships of OMIM gene-to-disease associations (dotted arrows) to equivalent DO terms via OMIM cross-references to DO terms (solid arrows).

Fig. 2.

Addition of ‘contributes to condition’ relations to DO. Prior to this project, OMIM cross-references in DO contained a mix of primarily disease records plus a few ‘susceptibility to disease’ records (shown on the left). The addition of the new relation allows disease cross-references to be computationally distinguished from relationships between a disease and a susceptibility to that disease (shown on the right). Solid lines represent cross-references; dotted lines represent the ‘contributes to condition’ relationship.

Fig. 3.

Addition of ‘located in’ axioms and the derivation of additional ‘is a’ disease relationships. Solid arrows indicate asserted relationships in DO; dashed lines indicate relationships inferred from anatomy-based axioms.