The mammalian phenotype ontology: enabling robust annotation and comparative analysis

Abstract

The mouse has long been an important model for the study of human genetic disease. Through the application of genetic engineering and mutagenesis techniques, the number of unique mutant mouse models and the amount of phenotypic data describing them are growing exponentially. Describing phenotypes of mutant mice in a computationally useful manner that will facilitate data mining is a major challenge for bioinformatics. Here we describe a tool, the Mammalian Phenotype Ontology (MP), for classifying and organizing phenotypic information related to the mouse and other mammalian species. The MP Ontology has been applied to mouse phenotype descriptions in the Mouse Genome Informatics Database (MGI, http://www.informatics.jax.org/), the Rat Genome Database (RGD, http://rgd.mcw.edu), the Online Mendelian Inheritance in Animals (OMIA, http://omia.angis.org.au/) and elsewhere. Use of this ontology allows comparisons of data from diverse sources, can facilitate comparisons across mammalian species, assists in identifying appropriate experimental disease models, and aids in the discovery of candidate disease genes and molecular signaling pathways.

Keywords: Annotation; Mammal; Model System; Ontology; Phenotype.

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 of genotypes and annotations to the term or any children of the term in MGI. The term path is displayed as a hierarchical tree. Note that since there are two paths to the term “opisthotonus”, each path appears as a unique hierarchical tree. Right, a graphical representation for the term “opisthotonus”. The two paths from the term to the top of the ontology can be seen.

Figure 2

Example of a MGI phenotype web page featuring MP term annotations. The Eng^tm1Mle (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 mutation organized by genotype. Specific systems can be expanded to reveal annotations to more granular terms. The Phenotypic data by genotype section lists the genotypes reported for this mutation, and expansion of this section reveals detailed annotations organized by systems and includes further descriptive annotations and reference data. Note that three cohorts of mice heterozygous for Eng^tm1Mle on different genetic backgrounds have been phenotypically analyzed. Distinct phenotypes were observed for this mutation on each of these unique genetic backgrounds.

Figure 3

Example of a MGI gene detail page highlighting summary mouse phenotype information. Gene Detail pages contain summary information about the gene with hyperlinks provided to more detailed information. Summary phenotype data includes the number of alleles listed by type of allele, a brief description of the generalized phenotypic effects of many mutations in the gene and links to mouse model of human disease information and to phenotype image data.

Figure 4

Example of phenotype annotations displayed on the Mouse Genome Browser. Left, a region of chromosome 14 including the Atxn7 gene is shown. Tracks representing high-level phenotypes of genes in this region are shown along with tracks indicating known alleles of the genes. The gene model graphics in the phenotype or allele tracks are hyperlinked to the allele record that describes that mutation, shown on the right.