Construction and accessibility of a cross-species phenotype ontology along with gene annotations for biomedical research

Abstract

Phenotype analyses, e.g. investigating metabolic processes, tissue formation, or organism behavior, are an important element of most biological and medical research activities. Biomedical researchers are making increased use of ontological standards and methods to capture the results of such analyses, with one focus being the comparison and analysis of phenotype information between species. We have generated a cross-species phenotype ontology for human, mouse and zebrafish that contains classes from the Human Phenotype Ontology, Mammalian Phenotype Ontology, and generated classes for zebrafish phenotypes. We also provide up-to-date annotation data connecting human genes to phenotype classes from the generated ontology. We have included the data generation pipeline into our continuous integration system ensuring stable and up-to-date releases. This article describes the data generation process and is intended to help interested researchers access both the phenotype annotation data and the associated cross-species phenotype ontology. The resource described here can be used in sophisticated semantic similarity and gene set enrichment analyses for phenotype data across species. The stable releases of this resource can be obtained from http://purl.obolibrary.org/obo/hp/uberpheno/.

Figure 1. Part a) illustrates the main idea how logical definitions and building block ontologies (left) cooperate in order to allow for reasoning procedures to infer new knowledge (right). Note that for the purpose of increased readability, only the term labels are shown and the ontology Uniform Resource Identifier (URIs) are skipped. Part b) illustrates an excerpt of the Uberpheno ontology to show how information on phenotype abnormalities in different organisms can be combined. It also illustrates how the annotations of genes can be transferred across different species by means of orthology relationships of genes. For example, after reasoning one could easily request all genes that are known to be related to the phenotype description "Bilateral microphthalmos" from the HPO. In Uberpheno "abnormally hypoplastic eye" from zebrafish (ZP) and "posterior microphthalmia" from MPO, are inferred to be subclasses of "Bilateral microphthalmos". These inferences can be used to infer that the genes tcf7l1a (zebrafish) and PRSS56 (mouse) are annotated to the phenotype "Bilateral microphthalmos" as well.

Figure 2.. Schematic work- and dataflow illustration for the construction of the Uberpheno ontology and the gene annotations.