Kemal Yaylali
07a01715fd
A table with filters made the user do the work. Rare disease triage is a different task:
which few variants could explain *this* patient's phenotype, and why. The app now answers
that, and lets a reviewer act on the answer.
Domain
- a case is a proband: a VCF plus the HPO terms observed in the patient (samples -> cases)
- HPO's gene-to-phenotype annotations are loaded as reference data (scripts/load-hpo.py)
- each candidate can be shortlisted or dismissed with a reason and a note
Ranking (app/services/triage.py, 21 tests)
- weighted sum of phenotype match, rarity, consequence severity and the model's score,
with every component shown next to the candidate
- rarity and consequence filter; phenotype only ranks, because a real diagnosis can sit in
a gene nobody has annotated yet and filtering on it would hide exactly that case
- ClinVar is deliberately not an input: it appears beside the result as independent
confirmation, so nothing ranks highly merely because ClinVar already said pathogenic
UI
- the funnel is the headline: variants called -> rare -> coding candidates -> phenotype-matched
- ranked candidates with evidence chips, not a grid of everything; filters are demoted
- a variant panel showing the score breakdown, the matched HPO terms, the raw VEP record and
links out to Ensembl/gnomAD/ClinVar, with the decision controls
- a printable case report: phenotype, funnel, shortlisted variants with reasons, provenance
API: /cases with phenotypes, /cases/{id}/candidates (funnel + ranked + weights),
/variants/{id}, /variants/{id}/decision, /cases/{id}/report, /phenotypes for the picker.
Scoring moved under the case and now answers 503 with the reason when no model registry is
reachable, instead of a 500.
Verified end to end on a simulated proband (scripts/make-demo-case.sh: real GIAB HG002
background + one real ClinVar 2-star pathogenic NF2 variant). 13 variants called -> 1 coding
candidate, and the planted variant ranks first at 0.80 on phenotype 1.00, rarity 1.00 and
consequence 1.00, with ClinVar agreeing afterwards.
Tests: api 75, ml 18, loader 16, web 27; ruff, mypy, svelte-check, terraform validate, both
kustomize overlays and the Nextflow stub run all clean.
64 lines
2.6 KiB
Python
64 lines
2.6 KiB
Python
from fastapi import APIRouter, HTTPException
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from sqlalchemy import func, select
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from sqlalchemy.dialects.postgresql import insert
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from sqlalchemy.orm import selectinload
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from app.db import SessionDep
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from app.models import Variant, VariantDecision
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from app.schemas import CandidateOut, DecisionIn, DecisionOut, VariantDetailOut
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from app.services import candidates as case_view
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from app.services import triage
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router = APIRouter()
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@router.get("/{variant_id}", response_model=VariantDetailOut)
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async def get_variant(variant_id: int, session: SessionDep) -> VariantDetailOut:
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"""Every piece of evidence for one variant, including the raw VEP record."""
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variant = await session.scalar(
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select(Variant)
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.where(Variant.id == variant_id)
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.options(
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selectinload(Variant.prediction),
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selectinload(Variant.decision),
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selectinload(Variant.job),
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)
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)
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if variant is None:
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raise HTTPException(404, "variant not found")
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case = await case_view.get_case(session, variant.job.case_id)
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terms = [p.hpo_id for p in case.phenotypes] if case else []
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gene_terms = await case_view.gene_terms_for(session, {variant.gene} if variant.gene else set())
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# evaluate, not rank: the panel must work for a variant that did not make the candidate list.
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scored = triage.evaluate(variant, terms, gene_terms)
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labels = {p.hpo_id: p.label for p in case.phenotypes} if case else {}
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base = CandidateOut.from_candidate(scored, labels).model_dump()
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return VariantDetailOut(**base, annotations=variant.annotations or {})
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@router.post("/{variant_id}/decision", response_model=DecisionOut)
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async def decide(variant_id: int, payload: DecisionIn, session: SessionDep) -> DecisionOut:
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if await session.get(Variant, variant_id) is None:
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raise HTTPException(404, "variant not found")
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stmt = insert(VariantDecision).values(
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variant_id=variant_id, state=payload.state, reason=payload.reason, note=payload.note
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)
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# Changing your mind replaces the call rather than failing on the unique constraint.
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await session.execute(
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stmt.on_conflict_do_update(
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index_elements=[VariantDecision.variant_id],
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set_={
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"state": stmt.excluded.state,
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"reason": stmt.excluded.reason,
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"note": stmt.excluded.note,
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"decided_at": func.now(),
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},
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)
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)
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await session.commit()
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decision = await session.scalar(
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select(VariantDecision).where(VariantDecision.variant_id == variant_id)
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)
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return DecisionOut.model_validate(decision)
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