The Mammalian Phenotype Ontology as a unifying standard for experimental and high-throughput phenotyping data

Abstract

The Mammalian Phenotype Ontology (MP) is a structured vocabulary for describing mammalian phenotypes and serves as a critical tool for efficient annotation and comprehensive retrieval of phenotype data. Importantly, the ontology contains broad and specific terms, facilitating annotation of data from initial observations or screens and detailed data from subsequent experimental research. Using the ontology structure, data are retrieved inclusively, i.e., data annotated to chosen terms and to terms subordinate in the hierarchy. Thus, searching for "abnormal craniofacial morphology" also returns annotations to "megacephaly" and "microcephaly," more specific terms in the hierarchy path. The development and refinement of the MP is ongoing, with new terms and modifications to its organization undergoing continuous assessment as users and expert reviewers propose expansions and revisions. A wealth of phenotype data on mouse mutations and variants annotated to the MP already exists in the Mouse Genome Informatics database. These data, along with data curated to the MP by many mouse mutagenesis programs and mouse repositories, provide a platform for comparative analyses and correlative discoveries. The MP provides a standard underpinning to mouse phenotype descriptions for existing and future experimental and large-scale phenotyping projects. In this review we describe the MP as it presently exists, its application to phenotype annotations, the relationship of the MP to other ontologies, and the integration of the MP within large-scale phenotyping projects. Finally we discuss future application of the MP in providing standard descriptors of the phenotype pipeline test results from the International Mouse Phenotype Consortium projects.

Fig. 1

The Mammalian Phenotype Ontology (MP) browser at MGI, showing details for the term “ventricular septal defect” (MP:0010402). Left MGI’s MP browser display shows the term name, common synonyms and acronyms, the primary MP ID, alternate IDs, and the term definition. The two term paths are shown as a hierarchial tree, with paths listed in multiple sequential graphs. Each term in the MP browser is followed by a link to MGI genotypes associated with that term or any children of that term. Right A graphical representation of the DAG structure for the term “ventricular septal defect.” The two alternate paths from the node “cardiovascular system phenotype” are shown

Fig. 2

Example of a MGI allele detail page and associated Human Disease and Mouse Model detail page. a The Fgfr2 ^tm1Schl (a mutation in the fibroblast growth factor receptor 2 gene, the first targeted mutation from the laboratory of Joseph Schlessinger) allele record shows nomenclature, a molecular description of the mutation, a phenotype summary organized by systems affected in tabular format to facilitate cross-genotype comparisons, a phenotype data by genotype section, a human disease model section, and associated references. b The phenotype by genotype section expands to reveal details, including further description and citations. Two different cohorts of mice carrying this allele have been analyzed, but only one has been asserted to be a model of the human disease Crouzon Syndrome (OMIM: 123500); links to both the MGI Human Disease and Mouse Model Detail page (c) and to OMIM are provided

Fig. 3

Example of a comprehensive MGI data search result using the term “ventricular septal defect.” Shown are samples of the results listed from this search. All 300 genotypes in MGI that are annotated to this term, or terms below this node in the MP, are returned. For example, genotypes annotated to the term “inlet ventricular septal defect,” a child term to “ventricular septal defect,” are seen in the results list