The homology search interfaces allow harmonised searches for GWAS and International Mouse Phenotyping Consortium (IMPC) mouse knockout genes associated with phenotypes of interest.

Phenotype Search

Human phenotypes can be searched using Medical Subject Headings (MeSH) and Human Phenotype (HP) ontology terms. Mouse phenotypes can be searched using Mammalian Phenotype (MP) ontology terms. Up to four terms can be submitted in a single search.

The search results will present the ontology term mapping (if present) and the number of GWAS studies and mouse knockout genes associated with the search term(s) and any mapped term(s).

Selecting the results report will open data tables of matching GWAS and mouse genes with links to more information in GWAS Central and the IMPC respectively. The mapping tab displays details about the cross-species ontology mapping if there is a direct mapping between the searched term and an equivalent term for the alternative species.

Phenotype Ontology Hierarchy

The ontology hierarchy interface is displayed across three panels:

• The left panel is used to search human phenotypes, which can be switched between MeSH and HP. Terms can be searched using the search box, or selected by browsing the ontology tree. Only ontology terms associated with GWAS, or mapped to mouse knockout genes, are displayed in the ontology tree. Icons next to terms in the tree indicate if human, mouse or human and mouse data is associated to the term (see icon key below).

• The right panel is used to search mouse phenotypes using MP. Terms can be searched using the search box, or selected by browsing the ontology tree. Only ontology terms associated with mouse knockout genes, or mapped to GWAS, are displayed in the ontology tree. Icons next to terms in the tree indicate if mouse or human and mouse data is associated to the term (see icon key below).

• The middle panel presents the search results. The data tab is separated into human GWAS studies and mouse knockout genes that are associated with the searched phenotype. The mapping tab displays details about the cross-species ontology mapping if there is a direct mapping between the searched term and an equivalent term for the alternative species.

Ontology tree icon key

	Human GWAS studies associated with term.
	Mouse gene knockouts associated with term.
	Human GWAS studies and mouse gene knockouts associated with term. Indirect (descendant) term mapping.
	Human GWAS studies and mouse gene knockouts associated with term. Direct term mapping, viewable from the mapping results tab.

Homology Genome View

The genome view is opened by selecting the “Genotype” button from the Phenotype Search or Ontology Hierarchy results report. GWAS markers and mouse genes associated with the selected phenotype are displayed as coloured bars in 3Mb bins along the human chromosomes. Selecting a coloured bar opens that region in the region view browser for higher resolution inspection.

Homology Region View

The region view browser is opened directly from the homology homepage or by selecting a region in the genome view. Tracks are provided to view GWAS Central variants and IMPC genes aligned along the human chromosomes.

For the IMPC mouse genes, the human gene orthologues are displayed. The human gene orthologues are retrieved from Ensembl which uses gene family and species trees to identify homologues which diverged by a speciation event (orthologues). More information about the Ensembl homology method is available from the Ensembl website.

Ontology Mappings

The subset of MP terms that are used to annotate IMPC mouse phenotypes are mapped to MeSH and HP using automated string matching and manual evaluation. The ontology mappings used by the homology interfaces are available in a tab-separated value text file here.