Integrating phenotype ontologies across multiple species

Abstract

Phenotype ontologies are typically constructed to serve the needs of a particular community, such as annotation of genotype-phenotype associations in mouse or human. Here we demonstrate how these ontologies can be improved through assignment of logical definitions using a core ontology of phenotypic qualities and multiple additional ontologies from the Open Biological Ontologies library. We also show how these logical definitions can be used for data integration when combined with a unified multi-species anatomy ontology.

Figure 1

OBO-registered ontologies of physical objects, from the molecular scale up to gross anatomical scale. Above the cellular level, anatomical ontologies are partitioned taxonomically (the full breadth of taxonomic coverage in OBO is not shown). For mammals there is a second bipartite division, between fully formed structures and developing structures. The former are represented in the Foundational Model of Anatomy (FMA) and the adult Mouse Anatomy (MA), and the latter in the Edinburgh Human Developmental Anatomy (EHDA) and the Edinburgh Mouse Atlas Project (EMAP) ontologies.

Figure 2

Example portion of the MP, and the equivalence relations between MP classes and EQ descriptions. Paths to the root over is_a links from 'Purkinje cell degeneration' and siblings. The is_a hierarchy is used for query-answering and genotype-phenotype analysis. Queries for 'neurodegeneration' or 'abnormal neuron morphology' should return genes or genotypes associated with 'Purkinje cell degeneration', such as the Pten gene. Note that prior to December 2008 MP lacked the highlighted link (indicated with the asterisk between two bold boxes), which resulted in false negatives for queries to 'neurodegeneration'. Using automated reasoning we were able to infer this link from the logical definitions and associated ontologies. We presented our results to the MP editors, who subsequently amended the ontology to include the link.

Figure 3

Equivalence relations between MP classes and EQ descriptions. Equivalence relations between two MP classes and their equivalent EQ descriptions. Here we treat MP 'degeneration' terms as in the PATO quality (Q) 'degenerate', rather than the process of degeneration. Here the bearer entities (E) are represented in the OBO Cell Ontology (CL). The EQ notation can be translated to logical expressions using Table 2. The dotted line indicates a relationship in the MP that can be independently inferred by a reasoner. CNS, central nervous system.

Figure 4

Process and anatomical phenotypes. (a) MP mixes process and anatomical/morphology phenotypes in the same is_a hierarchy. (b) MP-XP maps these to GO-BP and MA based descriptions respectively. (c) GO-BP to Uberon mappings make the link between the process class 'tooth development' and the general anatomical class 'tooth' explicit. (d) Uberon declaration stating that a mouse tooth is a subclass of the more general 'tooth' class.