PhenoHM: human-mouse comparative phenome-genome server

Abstract

PhenoHM is a human-mouse comparative phenome-genome server that facilitates cross-species identification of genes associated with orthologous phenotypes (http://phenome.cchmc.org; full open access, login not required). Combining and extrapolating the knowledge about the roles of individual gene functions in the determination of phenotype across multiple organisms improves our understanding of gene function in normal and perturbed states and offers the opportunity to complement biologically the rapidly expanding strategies in comparative genomics. The Mammalian Phenotype Ontology (MPO), a structured vocabulary of phenotype terms that leverages observations encompassing the consequences of mouse gene knockout studies, is a principal component of mouse phenotype knowledge source. On the other hand, the Unified Medical Language System (UMLS) is a composite collection of various human-centered biomedical terminologies. In the present study, we mapped terms reciprocally from the MPO to human disease concepts such as clinical findings from the UMLS and clinical phenotypes from the Online Mendelian Inheritance in Man knowledgebase. By cross-mapping mouse-human phenotype terms, extracting implicated genes and extrapolating phenotype-gene associations between species PhenoHM provides a resource that enables rapid identification of genes that trigger similar outcomes in human and mouse and facilitates identification of potentially novel disease causal genes. The PhenoHM server can be accessed freely at http://phenome.cchmc.org.

Figure 1.

Schematic representation of resources, workflow and methodology in PhenoHM server. The MPO terms are mapped to human phenotype terms in HPO and UMLS and OMIM records. For the mapped terms associated with mouse and human genes are extracted and compared to identify ortholog genes with orthologous phenotypes.

Figure 2.

Example of a phenotype mapping from MPO to HP and UMLS. The MPO tree view (A) and HPO tree view (B) show the granularity of concepts for cataract in the two ontologies. (C) The mapping of MPO term cataract to four different UMLS concepts as indicated by the unique CUIs and corresponding terms. (D) Overlap between cataract-associated genes of mouse and human. Of the 44 shared genes for cataract, 20 genes had known allelic variants associated with cataract.

Figure 3.

Network representation of orthologous phenotype network of cataract. The green and yellow colored nodes represent the mouse and human genes associated with cataract, respectively. The pink rectangles are the human allelic variants from OMIM, while the red triangles show the implicated mutation in human genes.