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.
49 lines
1.9 KiB
Python
49 lines
1.9 KiB
Python
import uuid
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from typing import Any
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from app.db import SessionLocal
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from app.models import Case, CasePhenotype, GenePhenotype, Job, JobStatus, Prediction, Variant
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VARIANT_DEFAULTS: dict[str, Any] = {
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"chrom": "22", "pos": 1, "ref": "A", "alt": "G", "gene": "NF2",
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"impact": "HIGH", "consequence": "frameshift_variant", "gnomad_af": None, "annotations": {},
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}
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async def seed_case(
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*,
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phenotypes: list[tuple[str, str]] | None = None,
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variants: list[dict[str, Any]] | None = None,
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gene_terms: dict[str, list[tuple[str, str]]] | None = None,
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status: JobStatus = JobStatus.succeeded,
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name: str | None = None,
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) -> tuple[uuid.UUID, uuid.UUID]:
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"""Insert a case, its phenotypes, a job and its variants. Returns (case_id, job_id).
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`variants` entries override VARIANT_DEFAULTS; a "score" key becomes a Prediction.
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"""
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async with SessionLocal() as s:
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case = Case(
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name=name or f"case-{uuid.uuid4()}",
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vcf_uri="gs://bucket/proband.vcf.gz",
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assembly="GRCh38",
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phenotypes=[CasePhenotype(hpo_id=hpo, label=label) for hpo, label in (phenotypes or [])],
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)
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job = Job(case=case, status=status, vep_version="113.0")
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s.add_all([case, job])
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for gene, terms in (gene_terms or {}).items():
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s.add_all(
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GenePhenotype(gene_symbol=gene, hpo_id=hpo, hpo_name=label) for hpo, label in terms
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)
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for spec in variants or []:
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fields = VARIANT_DEFAULTS | spec
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score = fields.pop("score", None)
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variant = Variant(job=job, **fields)
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s.add(variant)
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if score is not None:
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await s.flush()
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s.add(Prediction(variant_id=variant.id, model_name="rarelens-pathogenicity",
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model_version="demo", score=float(score)))
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await s.commit()
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return case.id, job.id
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