hpo-drift

What did a new HPO release change for your phenotype terms — and by how much did your similarity scores move?

The Human Phenotype Ontology is updated regularly. Terms get renamed, obsoleted and merged — and, the part nobody notices, the hierarchy gets new edges. New edges change information content, and information content is what Resnik and Lin similarity are made of. So the same patient set, scored against two HPO releases, gives different numbers even if none of your terms were touched. hpo-drift shows you exactly that, for the term list you actually use, in about three seconds.

The headline result

Feb 2026 → Jun 2026. The example is the HPO-annotated phenotype profile of chronic granulomatous disease (ORPHA:379): 22 phenotypic-abnormality terms straight from phenotype.hpoa. I chose CGD because the mechanism of its drift is clinically interpretable and fits in two sentences. Then, as a sanity check, hpo-drift cohort ran over the complete phenotype.hpoa corpus — 12 935 disease profiles, no size cutoff: 11 947 have at least one informative pair, 705 are single-term, 283 have root-only pairs, all of them stay in the table with a status — and hpo-drift rank ordered the rankable ones by mean |ΔLin|. CGD landed 50th of 11 947 (median profile 0.0013, 99th percentile 0.043). The rows above it are mostly small profiles of 2–12 terms, where one re-parenting moves a handful of pairs a lot; many of them are immunodeficiencies, because the immunology branch was restructured in this interval.

What happened to this profile, computed with Seco intrinsic IC on the is_a graph under Phenotypic abnormality:

• Two terms gained a parent. HPO introduced an Unusual infection hierarchy: Gingivitis (HP:0000230) is now also an Unusual oral cavity infection (HP:5210280), Sinusitis (HP:0000246) also an Unusual upper respiratory tract infection (HP:5210121). No label changed, nothing was obsoleted.
• Consequence: Gingivitis entered the immune branch. Its Lin similarity with Meningitis went 0.00 → 0.55, with Recurrent respiratory infections 0.00 → 0.46, with Sepsis 0.00 → 0.43 — their most-informative common ancestor is no longer the root but Unusual infection. Sinusitis ↔ Recurrent respiratory infections rose 0.48 → 0.78.
• IC moved for 18 of 22 terms (6 of them by more than 0.01; the other shifts come from N changing, and the 4 leaves stay at 1). All 95 informative pairs moved, 15 of them by more than 0.1; the remaining 136 pairs share only the root (ROOT_ONLY, 0 → 0). Mean |ΔLin| 0.067; the median disease profile: 0.0013.

The edit is clinically intuitive: gingivitis and sinusitis now connect more explicitly to the infection hierarchy. But even a sensible ontology improvement changes the numerical representation of a CGD phenotype profile, without changing the input phenotype profile. Pin the release tag in Methods, match on IDs, and report how much the numbers depend on the release. hpo-drift gives you that sentence with real figures; hpo-drift cohort tells you where your disease of interest sits.

Reproduce (the annotation file is pinned: phenotype.hpoa from HPO release v2026-06-23, #version: 2026-06-23, SHA-256 89004f85b253f980ffe84218d2c080665cbf67a57bbb322111d6a2db5eb31dff; the script prints the version and hash of the file it was given):

curl -LO https://github.com/obophenotype/human-phenotype-ontology/releases/download/v2026-06-23/phenotype.hpoa
hpo-drift cohort --hpoa phenotype.hpoa --old v2026-02-16 --new v2026-06-23 --out all_profiles.csv   # every profile, ~30 s
hpo-drift rank all_profiles.csv --metric mean_abs_dlin > ranked.csv                                  # optional

Output as run on 2026-09-03: examples/cohort-v2026-02-16_v2026-06-23.csv (all 12 935 profiles with status, plus a .meta.json recording the annotation file's version and hash) and examples/ranked-v2026-02-16_v2026-06-23.csv. Where familiar syndromes sit: X-linked agammaglobulinemia 0.033, autosomal dominant hyper-IgE syndrome 0.029, cystic fibrosis 0.023, Wiskott–Aldrich 0.020, Kabuki / Noonan / Marfan about 0.001.

30-second start

pip install hpo-drift

# one term per line — HP IDs (recommended) or labels
hpo-drift report --old v2026-02-16 --new v2026-06-23 --terms my_terms.txt

IC: Seco 2004 intrinsic, on the is_a graph under root HP:0000118 (Phenotypic abnormality); N = 18690 → 19120
active terms: 19389 → 19836 (added 469, obsoleted 22, renamed 266)
is_a edges:   +886 / −185

term        label        status     parents        IC old → new
HP:0000230  Gingivitis   unchanged  +HP:5210280    1.000 → 0.859
HP:0000246  Sinusitis    unchanged  +HP:5210121    1.000 → 0.880
…
pair                                   Lin old → new   Δ       MICA
Gingivitis ↔ Meningitis                0.000 → 0.553   +0.553  HP:0000118 → HP:0032158
Sinusitis ↔ Recurrent respiratory inf. 0.480 → 0.781   +0.301  HP:0012252 → HP:0011947
…

Add --json for a machine-readable report. Releases are pulled from the official GitHub assets of obophenotype/human-phenotype-ontology; any tag like v2026-06-23 works and is cached under ~/.cache/hpo-drift.

Three things it does

1 · report — the drift itself

Per term: status (unchanged / renamed / obsoleted → replacement / merged / missing), label change, parents added or removed, IC before and after. Per pair: Resnik and Lin in both releases, the delta, and the most-informative common ancestor — so you can see why a pair moved. Plus the ontology-wide counts.

2 · lint — hygiene for a term list

hpo-drift lint --release v2026-06-23 --terms my_terms.txt

⚠️ Arthritis: matched by LABEL — labels get renamed; store the ID → HP:0001369
❌ Recurrent infection: label not found (exact match on names/synonyms; the term is 'Recurrent infections')
❌ HP:0002961: OBSOLETE term → replaced_by HP:0010701

Exit code 1 on errors, so it works as a CI gate for a phenotype spreadsheet. Matching is exact on purpose: it reproduces the failure mode of a pipeline that matches by label. Store IDs, not labels: 266 labels changed in this interval alone, and fuzzy resolution (roadmap) must suggest, never auto-map.

3 · cohort and rank — the whole annotation corpus, no cutoffs

hpo-drift cohort --hpoa phenotype.hpoa --old v2026-02-16 --new v2026-06-23 --out all_profiles.csv
hpo-drift rank all_profiles.csv --metric mean_abs_dlin --top 20

cohort computes the drift summary for every disease in phenotype.hpoa (unique positive phenotypic-abnormality terms per disease). There is no minimum or maximum size: a profile that cannot support pairwise analysis stays in the table with a status — NO_USABLE_TERMS, TERM_ONLY (IC drift only), NO_INFORMATIVE_PAIRS (every pair shares only the root) or RANKABLE. Columns: raw / retained / missing / obsolete / out-of-domain term counts, IC changes, pairs split into informative and root-only, pairs changed and pairs moved by > 0.01 / > 0.1, mean and max |ΔLin|. rank is a separate, optional step over that complete table. report follows the same rules for any list you give it: 0, 1 or N terms, root-only pairs marked ROOT_ONLY, terms outside the root marked OUT_OF_DOMAIN with a pointer to --root.

4 · a monthly GitHub Action

.github/workflows/drift.yml fetches the latest release, compares it with your pinned one (PINNED_HPO) and uploads the report. Add a threshold on lin_delta from the JSON and it becomes a failing check.

How it works

flowchart LR
  A["release tag<br/>v2026-02-16"] -->|hp.obo| C[parse: terms · is_a · alt_id · obsolete]
  B["release tag<br/>v2026-06-23"] -->|hp.obo| C
  C --> D["intrinsic IC<br/>Seco 2004"]
  T[your term list] --> E[resolve IDs / labels]
  E --> F[per-term status · parents · IC Δ]
  D --> G[Resnik / Lin per pair · MICA · Δ]
  F --> R[report · JSON · lint]
  G --> R

IC is intrinsic (Seco et al. 2004: 1 − log(descendants+1)/log(N)), computed on the is_a graph only, with N and descendant counts taken inside the closure of a root — HP:0000118 Phenotypic abnormality by default (--root to change; inheritance, frequency and modifier branches are excluded, and the root's IC is exactly 0). Every report states the method, the root and N. Because this IC depends only on the graph, the drift measured here is caused purely by ontology edits, which is the effect this tool isolates. Annotation-based IC (from phenotype.hpoa) adds a second, independent source of drift and is the next option on the roadmap — then the two can be shown side by side.

Companion tools

• hpotools — HPO in R: release-pinned loading, similarity, Phenomizer-style ranking, enrichment.
• awesome-human-phenotype-ontology — link-verified list of HPO tools.

Roadmap

--ic annotations · fuzzy label suggestions in lint · Phenopackets v2 export · --pairs file for patient × disease scoring · JOSS paper.

Cite

DOI (all versions): 10.5281/zenodo.22286170 · this version: 10.5281/zenodo.22286739

Soloshenko M. hpo-drift: quantifying the effect of HPO release changes on phenotype-similarity results. 2026, v0.1.5. MIT License.