The Human Phenotype Ontology in 2021

Abstract

The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.

PolyQ length co-evolution in neural proteins

“…In proteins with multiple repeats, the total polyQ length was calculated as the sum of all the individual repeat lengths. Lists of human genes associated with gene ontology (GO) terms, human phenotype ontology (HPO) terms and specific diseases were derived, respectively, from the Gene Ontology AmiGO database (amigo.geneontology.org; 28 ), the HPO database (hpo.jax.org; 29 ) and the genome-wide association study (GWAS) Catalog database (ebi.ac.uk; 30 ). The GWAS Catalog entries were filtered to include only intragenic SNP and insertion/deletion (indel) mutations, either coding or non-coding, thus excluding intergenic mutations or non-univocal gene-phenotype/-disease associations.…”

Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities

“…The terms reported referring to biological processes linked to cytoskeleton activity and regulation. Four databases provided the list of ID-associated genes: HPO (Human Phenotype Ontology, in blue) [ 58 ], GEISINGER (in red) [ 59 ], OMIM (Online Mendelian Inheritance in Man, in green) [ 60 ], and SysID (in orange) [ 1 ]. *, **, and *** indicate p < 0.05, <0.01, and <0.001 respectively.…”

PhenCards: a data resource linking human phenotype information to biomedical knowledge

“…Some resources require regular updates and downloads to stay abreast of changes, but the majority of resources are API or web-based and require no changes to stay up-to-date Resource(s) Method of access Update needed? Content HPO [ 4 , 13 ] (includes OMIM [ 3 , 21 ] and Orphanet [ 2 ]), Disease Ontology [ 19 , 20 ] Elasticsearch [ 25 ] on indexed database Yes, monthly Standardized phenotype and disease terms ICD-10 [16], UMLS [ 17 , 18 ], OHDSI ATHENA [ 15 ], MeSH [ 14 ] Elasticsearch on indexed database Yes, yearly Standardized phenotype and disease terms Pharos (disease) [ 30 ] API No Disease aliases, expression, drug, pathway, Gene Ontology data IRS (Internal Revenue Service), Open990 Elasticsearch on indexed database Yes, yearly Nonprofit grants and foundations NIH (National Institute of Health) Federal Reporter, NIH FOAs (funding opportunity announcements) API No Federal grant and projects Direct2Experts [ 31 ] API No Collaborators, specialty physicians openFDA [ 32 ], Tocris, APExBio, Pharos (target) [ 30 ], DrugCentral [ 33 ] API No Federal and company drug, drug target and adverse effect data Pathway Commons [ 34 ] and KEGG [ 5 , 34 ] API No Pathways: diseases, biological functions ClinicalTrials.gov [ 35 ] API No …”

“…Phenotype vocabularies are superb tools for facilitating the investigation and classification of genetic diseases. Copious web servers, databases, and other resources for phenotypic terms and diseases exist: HPO (Human Phenotype Ontology) [ 4 , 13 ], MeSH (Medical Subject Headings) [ 14 ], OHDSI (Observational Health Data Sciences and Informatics) [ 15 ], ICD-10 (International Classification of Diseases, version 10) [ 16 ], UMLS (Unified Medical Language System) [ 17 , 18 ], Disease Ontology [ 19 , 20 ], OMIM (Online Mendelian Inheritance in Man) [ 3 , 21 ], DECIPHER (DatabasE of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resource) [ 22 ], and Orphanet [ 2 ]. However, few of them link related biomedical information to disease and phenotypic terms, and there are numerous gaps in information.…”