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Human Phenotype Ontology Overview

The Human Phenotype Ontology (HPO) provides standardized identifiers for clinical abnormalities and connects them in a structured hierarchy. Folklore uses these identifiers to compare a patient's observed findings with gene-associated phenotype profiles.

Terms and Relationships

Each HPO concept has an identifier, a preferred name, synonyms, and relationships to broader or more specific concepts. For example, a specific seizure type sits below the broader term "Seizure". These relationships allow clinically related findings to contribute to a match without requiring identical wording.

A specific, observed finding is usually more informative than a broad ancestor term. HPO is a vocabulary for phenotype description, not a diagnosis code and not a substitute for clinical interpretation.

How Terms Enter Folklore

Search by name, synonym, or identifier

The clinical profile search resolves current HPO terms and excludes obsolete entries from suggestions.

Extract findings from free text

Folklore can propose clinical findings from pasted text and map them to HPO. If that path is unavailable, a local ontology-based fallback is used.

Review before analysis

Automatic extraction is an aid, not a final clinical profile. Confirm the concept, specificity, and whether the finding is actually present before accepting it.

Reuse gene associations

Variant Analysis attaches gene-associated HPO profiles to eligible variants. Phenotype Matching compares the patient profile against those annotations.

Negated Findings Need Manual Review

Do not add an absent or explicitly negated feature as a present HPO term. Automatic extraction can miss contextual negation, especially in complex clinical text. Folklore's phenotype score currently evaluates selected positive findings; it does not use absent findings as exclusion evidence.

Data Boundaries

Ontology coverage

Matching is limited to HPO concepts and gene-phenotype associations available to the analysis environment.

Annotation maturity

Recently described genes and phenotypes may have incomplete profiles and can be under-ranked.

Unresolved identifiers

HPO identifiers that cannot be resolved are omitted from the similarity calculation.

Clinical context

Age, onset, severity, and inheritance remain important even when they are not fully represented by the selected terms.

Reference

Kohler S, et al. "The Human Phenotype Ontology in 2024: phenotypes around the world." Nucleic Acids Research. 2024;52(D1):D1333-D1346. PMID: 37953324.