The Mammalian Phenotype Ontology (MPO) supports “robust annotation of mammalian phenotypes in the context of mutations, quantitative trait loci and strains that are used as models of human biology and disease. … It continues to develop dynamically via collaborative input from research groups, mutagenesis consortia, and biological domain experts. (see citation)” The MPO is a broad list of categories focused on mammalian expressed phenotype. Its particular focus is on those phenotypes having been investigated in the context of the defined, controlled mouse strains curated by the Jackson Laboratories (JAX) and to annotate records in the Rat Genome Database.

The staff of the Mouse Genome Informatics group at the Jackson Laboratories (JAX) in Bar Harbor, Maine has curatorial responsibility for the MPO.

Primary citation:

Smith CL, Goldsmith C-AW and Eppig JT (2004) The Mammalian Phenotype Ontology as a tool for annotating, analyzing and comparing phenotypic information. GenomeBiology. 6:R7 (http://genomebiology.com/2004/6/1/R7).

The MPO is constructed using a hierarchical tree structure, where some of the individual concepts can be located in more than one location in the overall hierarchy (a directed, acyclic graph or DAG). For instance, “abnormal pancreas secretion” appears both under the broad categories “digestive/alimentary phenotype” and “endocrine/exocrine gland phenotype.” As of August, 2005, the MPO consists of 4175 unique terms with definitions linked via 6125 relationships. There are also 5143 term synonyms [ ftp://ftp.informatics.jax.org/pub/reports/index.html#nomen]. JAX uses DAG-Edit (v1.418) [http://geneontology.sourceforge.net/] from the Gene Ontology Consortium to maintain the concepts in this structure.

From the citation given above (with liberal paraphrasing by BB): “Our goal is to (use a directed acyclic graph organization of concepts in order to) describe the richness of phenotypes as precisely as they are known, recognizing that phenotype data are by nature complex and usually incomplete.… Each MPO term has a unique identifier, a definition and synonyms. …(We seek) to address two practical implementation questions. From the biologist's perspective, the question is what term would be used to describe a specific phenotypic trait. From the curatorial perspective, we ask what terms reflect biological reality and maximize curator productivity. From a purely ontological perspective, every trait could be broken down into a core object, such as 'cornea' or 'gastrulation', defined by anatomical, behavioral or physiological terms, and a series of attribute vocabularies that describe the quality, quantity and character of a trait. For the practical reason of needing robust terms to describe phenotypes up-front to speed curation and the problem of losing biological meaning, particularly for clinical or dysmorphology terms, when terms are completely deconstructed (that is, the sum of the parts is less than the term itself), we have chosen to use compound terms in the MP Ontology (e.g., dystrophic cardiac calcinosis. these terms requires multiple annotations to recover all aspects that the single term provides. Use of complex terms in the MP Ontology, however, does not preclude also storing the decomposed version should this later prove desirable. More important, the MP Ontology can currently hold, for each term, database cross-references to other ontologies. This is a common practice in the Gene Ontology (GO) when compound terms are developed. For the MP Ontology, these cross-references include anatomical terms from the Mouse Anatomy ontologies and the GO process terms. (We pursue three strategies): (1) Follow the evolving literature to identify newly described phenotypic traits. New terms added in this way may be a simple addition to an existing hierarchical path or may result in the addition of entire new branches in the hierarchy; (2) collaborative efforts between the MGD phenotype curators, the mouse mutagenesis centers and the rat genetics community identify new specific terms and suggest improved organization of terms within particular hierarchical branches; (3) recruit individuals with expertise in specific biological domains to review and evaluate sections of the vocabulary for accuracy, completeness and systematic arrangement. … While common pathological and clinical terms are used in the MP Ontology, considerations for term placement within the structure and for precise terminology is often derived from comparison with other open biological ontologies (OBO). Recently, a cell-type ontology has become available and a comparison of terminology to this ontology has not yet been completed. We are working with the mutant mouse pathology database Pathbase to map and cross-reference terms from their Pathology Ontology.”

It is primarily used by JAX to annotate a database monitoring studies in the literature of specific alleles found in their defined mouse strains. “The MP Ontology is currently used by the Mouse Genome Database and Rat Genome Database to represent phenotypic data. As of 1 November 2004, over 11,150 phenotypic alleles representing mutations in 5,214 unique genes had been catalogued in MGD. For these alleles, 9,696 genotype records exist, with 21,556 phenotypic annotation instances. (It) is also used in phenotypic data annotations at the Rat Genome Database (RGD) (see citation).” The MPO has also been used by other groups developing ontological resources for mammalian phenotype, for instance those working on the Human Proteome Survey Database (HumanPSD).

An example of how JAX uses this ontology follows: A term for 'decreased dopamine level [ID = MP:0005643]' exists in the following location in the Mammalian Phenotype hierarchy:

Phenotype Ontology --> nervous system phenotype --> abnormal nervous system physiology --> abnormal dopamine level --> decreased dopamine level [http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=mpAnnotSummary&id=MP:0005643].

This term has been used to annotate 7 records in their allele-to-publication database [http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=mpAnnotSummary&id=MP:0005643].

An example of 1 such record links the research article Fon EA, Pothos EN, Sun BC, Killeen N, Sulzer D, Edwards RH (1997) N Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action. Neuron 19(6):1217-1283, Dec. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9427250&dopt= Abstract]

to the allele: Slc18a2tm1Edw - targeted mutation 1, Robert H Edwards - synonyms: VMAT2-, VMAT2KO (MGI:3574768) [ http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=alleleDetail&id=MGI:3574768] and relates to a cross of the following strains: C57BL/6 X 129X1/SvJ C57BL/6 - member of C57BL group [http://www.informatics.jax.org/external/festing/mouse/docs/C57BL.shtml] 129X1/SvJ - member of 129 group [http://www.informatics.jax.org/external/festing/mouse/docs/129.shtml] where the progeny studied were homozygous for the above allele.

A. Within a Test Bed:

Linking to this concept in the MP ontology ('decreased dopamine level') can be used by a group working on the alpha synuclein-SNCA model of Parkinson's disease. It provides a link to both literature and mouse strain/allelic entities specified in the MGI database. This in turn can be used to further link to relevant terms from other ontologies that JAX has used to annotate these same records (The Gene Ontology and their Standard Anatomical Database). These links can then be analyzed for statistical correlations, filter on other information relevant to the focus of this test bed (“Parkinson's Disease”, specific anatomical or ultrastructural abnormalities) which could lead to uncovering relevant links to existing work in the literature. Other relevant concepts from this ontology can be deduced based on the mouse strains under study. These can be applied to the strain/allele --> MP concept map maintained by JAX to further uncover novel phenotypic concepts that may prove relevant to the specific study in hand.

B. Across Test-Beds:

Using concepts from this controlled ontological repository can aid in data integration across test beds, wherever a shared phenotypic characteristic is found in this ontology. (There are other issues here but I've run out of time right now - I'll add to it later. Others more intimately acquainted with the scientific details of each test bed are better suited to identify ‘within’ and across test bed benefits.

Both 'A' & 'B' above can be of value in providing powerful and useful functionality to end users via the Smart Atlas.