The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

Abstract

The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online.

Leigh map: A novel computational diagnostic resource for mitochondrial disease

“…To facilitate data collection from this large breadth of literature associated with Leigh syndrome, we performed systematic literature mining with QDA Miner Lite (v1.4.2; Provalis Research, Montreal, Quebec, Canada) to generate a list of genes reported to cause Leigh syndrome or Leigh‐like syndromes, and their corresponding phenotypes. Phenotypic information was standardized by manually entering each reported phenotype into Phenomizer (compbio.charite.de/phenomizer),11, 12 a free online resource, which catalogues thousands of standardized human phenotypes, to obtain the appropriate HPO term and number. In addition to obtaining individual Leigh syndrome genes and phenotypes, we collected information on additional parameters that will give users further insight for an informed diagnosis.…”

“…Examples of gene categories that can be found on the Leigh Map include genes involved in oxidative phosphorylation (eg, NDUFA1, SDHA ) and genes that maintain mitochondrial DNA (eg, POLG, SUCLA2 ; see Fig 2). Expression of Leigh syndrome phenotypes in HPO terms11, 12 serves to normalize the network, thereby eliminating discrepancies in clinical jargon for phenotypes for which >1 synonym exists. “Leukodystrophy,” for example, can be described alternatively as “leukoencephalopathy” or “white matter changes.” The use of different nomenclature varies among clinicians and in different geographical regions; therefore, the use of a single HPO term (leukodystrophy; HP: 0002415) simplifies the Leigh Map and encourages its widespread utilization (Fig 3).…”

“…The network comprises 89 genes and 236 phenotypes, expressed in Human Phenotypic Ontology (HPO) terms,11, 12 providing sufficient phenotypic and genetic variation to test the network's diagnostic capability. The Leigh Map aims to enhance the interpretation of WES data to aid clinicians in providing faster and more accurate diagnoses for patients so that appropriate measures can be taken for optimal management.…”

Gene2DisCo: Gene to disease using disease commonalities

“…In general, a disease hierarchy may posses different structures (forest of trees like MeSH hierarchy, direct acyclic graph like the Human Phenotype Ontology [55], etc.) and can be represented by a graph H = (C, E), where C = {1, 2, .…”

Estrogen-related receptor gamma implicated in a phenotype including hearing loss and mild developmental delay

“…DGAP242's clinical description and refined translocation breakpoints are deposited in DECIPHER (decipher.sanger.ac.uk/patient/317883). 7 Lymphoblastoid cell line …”