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.
98 lines
3.5 KiB
Python
98 lines
3.5 KiB
Python
"""The serverless track: the API starts a Cloud Run job instead of publishing to Pub/Sub."""
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import uuid
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from typing import Any
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import pytest
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from httpx import AsyncClient
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from app.config import settings
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from app.services import events
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class FakeOperation:
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def __init__(self, execution: str) -> None:
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self.metadata = type("Meta", (), {"name": execution})()
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class FakeJobsClient:
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def __init__(self, result: Any = None) -> None:
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self.result = result
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self.requests: list[dict] = []
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def run_job(self, request: dict) -> FakeOperation:
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self.requests.append(request)
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if isinstance(self.result, Exception):
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raise self.result
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return self.result
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async def new_case(client: AsyncClient) -> str:
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r = await client.post(
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"/api/cases",
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json={"name": f"s-{uuid.uuid4()}", "vcf_uri": "gs://bucket/x.vcf.gz", "assembly": "GRCh37"},
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)
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assert r.status_code == 201, r.text
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return r.json()["id"]
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@pytest.fixture
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def cloudrun(monkeypatch: pytest.MonkeyPatch) -> None:
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monkeypatch.setattr(settings, "pubsub_topic", None)
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monkeypatch.setattr(settings, "cloudrun_job", "rarelens-nextflow")
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monkeypatch.setattr(settings, "gcp_project", "my-proj")
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monkeypatch.setattr(settings, "gcp_region", "europe-west2")
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@pytest.mark.usefixtures("db", "cloudrun")
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async def test_annotate_executes_the_job_with_pipeline_arguments(
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client: AsyncClient, monkeypatch: pytest.MonkeyPatch
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) -> None:
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jobs = FakeJobsClient(FakeOperation("projects/p/locations/l/executions/rarelens-nextflow-abc12"))
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monkeypatch.setattr(events, "_jobs_client", lambda: jobs)
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case_id = await new_case(client)
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r = await client.post(f"/api/cases/{case_id}/annotate")
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assert r.status_code == 202
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job = r.json()
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assert job["status"] == "running"
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assert job["workflow_ref"] == "cloudrun:rarelens-nextflow-abc12"
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[request] = jobs.requests
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assert request["name"] == "projects/my-proj/locations/europe-west2/jobs/rarelens-nextflow"
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[override] = request["overrides"]["container_overrides"]
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args = override["args"]
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assert args[:4] == ["run", "/pipeline/main.nf", "-profile", "gcp"]
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assert args[args.index("--job_id") + 1] == job["id"]
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assert args[args.index("--assembly") + 1] == "GRCh37"
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assert args[args.index("--vcf") + 1] == "gs://bucket/x.vcf.gz"
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@pytest.mark.usefixtures("db", "cloudrun")
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async def test_a_failed_execution_call_marks_the_job_failed(
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client: AsyncClient, monkeypatch: pytest.MonkeyPatch
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) -> None:
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monkeypatch.setattr(
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events, "_jobs_client", lambda: FakeJobsClient(RuntimeError("403 permission denied"))
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)
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case_id = await new_case(client)
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job = (await client.post(f"/api/cases/{case_id}/annotate")).json()
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assert job["status"] == "failed"
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assert "403 permission denied" in job["log"]
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@pytest.mark.usefixtures("db", "cloudrun")
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async def test_cloud_run_job_takes_precedence_over_pubsub(
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client: AsyncClient, monkeypatch: pytest.MonkeyPatch
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) -> None:
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monkeypatch.setattr(settings, "pubsub_topic", "vcf-uploaded")
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jobs = FakeJobsClient(FakeOperation("projects/p/locations/l/executions/x-1"))
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monkeypatch.setattr(events, "_jobs_client", lambda: jobs)
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monkeypatch.setattr(
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events, "_publisher", lambda: pytest.fail("Pub/Sub must not be used in the serverless track")
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)
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case_id = await new_case(client)
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assert (await client.post(f"/api/cases/{case_id}/annotate")).json()["status"] == "running"
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assert len(jobs.requests) == 1
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