The description of mouse phenotypes in databases should be captured such that we can compare, combine and analyze biologically relevant information from divergent sources. For example, published reports vary significantly in the level of detail and breadth of data, while high-throughput phenotyping centers thoroughly test a limited number of specific parameters. Phenotype descriptions should be standardized to allow complex queries using other integrated data types such as sequence, genomic location and/or biological function of gene products. Such standard phenotype descriptions must have accurate and precise lexical syntax, yet be applicable to multiple organisms to allow cross-species comparisons. To address this problem, we developed the Mammalian Phenotype Ontology (MP) to describe abnormal mammalian phenotypes. [27
The Mammalian Phenotype Ontology (MP) is a standardized structured vocabulary. MP terms are organized into a directed acyclic graph (DAG) with terms placed hierarchically from the very general at the top of the graph to more specific terms as one moves down the structure. The highest level terms describe physiological systems, survival, and behavior. The physiological systems branch into morphological and physiological phenotype terms at the next node level. A browser is available to view the MP at (http://www.informatics.jax.org/searches/MP_form.shtml
) and a sample page is shown in . Each vocabulary term includes a unique accession ID, term name, synonyms and definition. The relationship to child nodes and parent nodes is also represented. Any term with more than one parent is shown in multiple sequential graphs.
Figure 1 Mammalian Phenotype Ontology, showing details for the term “opisthotonus” [MP:0002880]. Left, MGI Browser display shows the term name, common synonyms, the MP ID and the term definition. Each term is followed by a link indicating the number (more ...)
The organization of the MP allows annotation of data to the level of resolution available, whether general or highly specific. For example, a published phenotype referred to as “moderate behavioral impairment” may be annotated to the high level term “abnormal behavior” [MP:0004924] while a more detailed description of “opisthotonus” [MP:0002880] could be used if more specific observations or studies had been done. Each term shown in the browser is followed by a hypertext link listing the number of genotype annotations in MGI to each term or to a child of that term (, “opisthotonus” has 12 annotations to 12 different genotypes, as of this writing). This hypertext link leads to a list of mouse genotypes annotated in MGI and the annotated term and reference(s) cited for that annotation. This feature allows a narrow or broad search that can return genotypes annotated to detailed phenotypic descriptions or to genotypes that have less well-characterized data.
In MGI, mouse phenotype data are annotated to genotype objects. Each genotype consists of one or more mutant allele pairs combined with associated genetic background strain information. Each MP term annotated to a genotype is supported by one or more references and may also include additional unstructured notes that describe specific comparative details such as incidence, experimental conditions, e.g., diet or stressor, age of onset or quantitative values. shows an example of MP annotations to genotypes involving the Engtm1Mle mutant allele (the first targeted mutation of the endoglin gene made in the Michelle Letarte laboratory). Users can view information about the Engtm1Mle mutant allele from two perspectives on its allele detail page: 1) The phenotype summary section presents a matrix view showing phenotypes (MP Ontology terms) on one axis and genotypes involving Engtm1Mle on the other axis. Using the expansion toggles to view more or fewer specific MP terms, it is easy to compare across genotypes to observe similarities or differences. 2) The phenotype data by genotype section lists each genotype that involves Engtm1Mle that has been phenotypically characterized. Links in the genotype column lead to the greatest detail available for descriptions of that genotype, including MP annotations and additional annotated detail. If an author states that a particular mouse genotype is a model of human disease or syndrome, an association with an Online Mendelian Inheritance in Man (OMIM) human disease term is made, and links to both OMIM and MGI’s Human Disease and Mouse Model Detail pages are provided. In addition, published images highlighting phenotype data are frequently associated with both allele and genotype records. Each of these phenotype sections is organized by the biological system affected and is based on the structure of the MP Ontology. As of 12/20/08, MGI contained 139,751 MP annotations to 27,778 genotypes, representing 20,987 independent alleles, and 8,286 genes and 4,023 QTL ().
Figure 2 Example of a MGI phenotype web page featuring MP term annotations. The Engtm1Mle (endoglin gene, targeted mutation 1, Michelle Letarte) allele record shows phenotype data organized in two ways. A tabular Phenotype summary lists systems affected by the (more ...)
Phenotypes, Alleles & Disease Models at MGI
In addition to mouse data, the Mammalian Phenotype Ontology has been used to classify phenotype data from rat and other mammalian species (RGD, OMIA). Species-specific terms are included in the MP. For example, species such as rodents, felines and others exhibit vibrissae while primates do not. In such cases, annotations can be made to vibrissae-related terms when appropriate to a species and ignored when the terms do not apply. The MP also contains related species-specific terms such as the primate-specific term abnormal menstrual cycle [MP:0003375 and the term abnormal estrous cycle [MP:0001927] that is applicable to many other non-primate mammals. By using the parent term abnormal ovulation cycle [MP:0009344] data annotated to this parent term and both of its children could be retrieved from multiple sources.
The MP Ontology, as well as other commonly used biomedical ontologies (e.g
., GO, MA, and CL), is maintained using the OBO-Edit software developed by Lewis and Richter [11
]. Daily edits include the addition of new term and synonyms, new relationships based on comparisons to orthogonal ontologies and revisions to existing terms. We adhere to Open Biomedical Ontologies (OBO) Foundry principles (http://www.obofoundry.org/about.shtml
) in the construction and revision of the ontology, such as orthogonality, public availability and collaborative development [26
]. In addition to the MP browser mentioned above, the MP ontology is available in OBO format from the MGI ftp site (ftp://ftp.informatics.jax.org/pub/reports/index.html#pheno
) and in OBO and OWL (Web Ontology Language) format from the OBO Foundry site (http://www.obofoundry.org/cgi-bin/detail.cgi?id=mammalian_phenotype
We continue to refine and expand the MP. Current users of the ontology, including curators from MGI, RGD and the Neuromice Consortium have contributed terms. In addition to curator and community suggestions, we are actively soliciting participation from collaborators and researchers in various fields of specialty to review existing portions of the ontology for accuracy in terminology, completeness and the correct hierarchical structure. We have recently completed a review of the hearing and ear morphology section of the ontology with assistance from Dr. Kenneth Johnson at The Jackson Laboratory and Dr. Karen Steel at the Wellcome Trust Sanger Institute. With this review, 253 new hearing and ear morphology and physiology terms were added, and the associated structural hierarchy for all 387 hearing and ear related terms was reorganized. Review of the cardiovascular and immunology sections of the MP Ontology is underway. A term tracker for all community MP Ontology requests has been established at Sourceforge (https://sourceforge.net/tracker/?atid=1109502&group_id=76834&func=browse
). Additional information may be obtained by emailing pheno/at/informatics.jax.org