Phenotype Profiles

This ingest aggregates phenotype profile data from curated sources. Currently it includes data from the Human Phenotype Ontology Annotations (HPOA).

HPOA

The Human Phenotype Ontology group curates and assembles over 115,000 annotations to hereditary diseases using the HPO ontology. This ingest transforms HPOA data into gene-phenotype, disease-phenotype, gene-disease, and disease-inheritance associations.

Data Sources

• HPOA genes_to_phenotype.txt
• HPOA genes_to_disease.txt
• HPOA phenotype.hpoa
• Mondo SSSOM mappings (for disease ID normalization)
• HP ontology (for inheritance term validation)

Gene to Phenotype

Gene-to-phenotype associations derived from HPOA, with disease context preserved. A preprocessing step joins the genes_to_phenotype file with disease mappings and Mondo SSSOM to normalize disease IDs to MONDO where possible (ORPHA: prefixes are also normalized to Orphanet: for SSSOM compatibility).

Frequency data is captured in multiple forms: as HPO frequency qualifier terms (HP:0040280-HP:0040285), as percentages, or as counts/totals from cohort data.

Biolink Captured:

• biolink:GeneToPhenotypicFeatureAssociation
  • id (UUID)
  • subject (NCBIGene:{id})
  • predicate (biolink:has_phenotype)
  • object (HPO term ID)
  • disease_context_qualifier (MONDO or original disease ID)
  • frequency_qualifier (HPO frequency term, when available)
  • has_percentage (percentage, when available)
  • has_quotient (quotient, when available)
  • has_count (numerator from cohort ratio, when available)
  • has_total (denominator from cohort ratio, when available)
  • publications
  • primary_knowledge_source (infores:hpo-annotations)
  • aggregator_knowledge_source (["infores:monarchinitiative"])
  • knowledge_level (logical_entailment)
  • agent_type (automated_agent)

Disease to Phenotype

Disease-to-phenotype associations from the phenotype.hpoa file, filtered to only "P" (phenotypic anomaly) aspect records. Includes rich annotation data: evidence codes, sex qualifiers, onset, and frequency information.

The primary knowledge source is determined by the disease ID prefix: OMIM diseases use infores:omim, Orphanet diseases use infores:orphanet, and DECIPHER diseases use infores:decipher.

Biolink Captured:

• biolink:DiseaseToPhenotypicFeatureAssociation
  • id (UUID)
  • subject (disease ID, with ORPHA: normalized to Orphanet:)
  • predicate (biolink:has_phenotype)
  • negated (true when qualifier is "NOT")
  • object (HPO term ID)
  • has_evidence (ECO term mapped from 3-letter evidence code)
  • sex_qualifier (PATO term: PATO:0000383 female, PATO:0000384 male)
  • onset_qualifier (HPO onset term, when available)
  • frequency_qualifier (HPO frequency term, when available)
  • has_percentage, has_quotient, has_count, has_total (frequency data)
  • publications
  • primary_knowledge_source (determined by disease prefix)
  • aggregator_knowledge_source (["infores:monarchinitiative", "infores:hpo-annotations"])
  • knowledge_level (knowledge_assertion)
  • agent_type (manual_agent)

Evidence Code Mapping

HPOA Code	ECO Term	Label
IEA	ECO:0000501	inferred from electronic annotation
PCS	ECO:0006017	published clinical study evidence
TAS	ECO:0000304	traceable author statement
ICE	ECO:0006019	individual clinical experience evidence

Gene to Disease

Gene-to-disease associations from the HPOA genes_to_disease file. The association type determines the Biolink class and predicate:

Association Type	Biolink Class	Predicate
MENDELIAN	CausalGeneToDiseaseAssociation	biolink:causes
POLYGENIC	CorrelatedGeneToDiseaseAssociation	biolink:contributes_to
UNKNOWN	CorrelatedGeneToDiseaseAssociation	biolink:gene_associated_with_condition

The primary knowledge source is derived from the source column: medgen sources map to infores:omim (with infores:medgen as additional aggregator), orphadata sources map to infores:orphanet.

Biolink Captured:

• biolink:CausalGeneToDiseaseAssociation / biolink:CorrelatedGeneToDiseaseAssociation
  • id (UUID)
  • subject (NCBIGene ID)
  • predicate (mapped from association type, see above)
  • object (disease ID, with ORPHA: normalized to Orphanet:)
  • primary_knowledge_source (derived from source column)
  • aggregator_knowledge_source (includes infores:monarchinitiative)
  • knowledge_level (knowledge_assertion)
  • agent_type (manual_agent)

Disease Mode of Inheritance

Disease-to-inheritance associations from the phenotype.hpoa file, filtered to "I" (inheritance) aspect records. Only rows where the HPO term is a descendant of "Mode of inheritance" (HP:0000005) in the HP ontology are included.

Biolink Captured:

• biolink:DiseaseOrPhenotypicFeatureToGeneticInheritanceAssociation
  • id (UUID)
  • subject (disease ID)
  • predicate (biolink:has_mode_of_inheritance)
  • object (HPO inheritance term ID)
  • has_evidence (ECO term mapped from evidence code)
  • publications
  • primary_knowledge_source (infores:hpo-annotations)
  • aggregator_knowledge_source (["infores:monarchinitiative"])
  • knowledge_level (knowledge_assertion)
  • agent_type (manual_agent)

HPOA Citation

Kohler S, Gargano M, Matentzoglu N, Carmody LC, Lewis-Smith D, Vasilevsky NA, Danis D, et al. The Human Phenotype Ontology in 2024: Phenotype-Based Knowledge for Rare Disease Discovery. Nucleic Acids Research. 2024;52(D1):D1333-D1346. doi: 10.1093/nar/gkad1005. PMID: 37953324

License

BSD-3-Clause