"Variants are unscored" was accurate: nothing was ever trained, so a quarter of every rank was dead weight and the UI leaked a connection error at the reader. - scripts/make-training-set.sh derives a training table from ClinVar directly. ClinVar already carries the molecular consequence, the gene and an allele frequency, which is the feature set serving sends, so this avoids running VEP over hundreds of thousands of variants. 2-star records only. - train.py now holds out whole genes (GroupShuffleSplit). docs/data.md had said to do this since the data pass; the code was still doing a random split, which is the leak Grimm 2015 describes. - evaluate() reports missense on its own. On the last run: AUROC 0.986 over 74,239 held-out variants, but 0.872 over the 13,553 missense ones, and the docs say plainly why even that is flattered — within missense the only live feature is allele frequency, and ClinVar's benign calls often use allele frequency as evidence (ACMG BA1/BS1), so the feature partly caused the label. - the 503 now names what is missing (model@alias via tracking URI) and leaves the exception in the server log instead of the UI. - make training-set / make train; the 58 MB table is gitignored. Verified end to end: model registered as v2, the simulated NF2 case scores 0.999 on the planted variant, and it now ranks 1.00 with all four components live. Tests: api 77, ml 22, loader 16, web 32; ruff, mypy, svelte-check clean.
240 lines
8.7 KiB
Python
240 lines
8.7 KiB
Python
import logging
|
|
import uuid
|
|
from dataclasses import asdict
|
|
from datetime import UTC, datetime
|
|
|
|
from fastapi import APIRouter, HTTPException, Query, status
|
|
from sqlalchemy import func, select
|
|
from sqlalchemy.exc import IntegrityError
|
|
from sqlalchemy.orm import selectinload
|
|
|
|
from app.config import settings
|
|
from app.db import SessionDep
|
|
from app.models import (
|
|
Case,
|
|
CasePhenotype,
|
|
DecisionState,
|
|
Job,
|
|
JobStatus,
|
|
Variant,
|
|
VariantDecision,
|
|
)
|
|
from app.schemas import (
|
|
CandidateOut,
|
|
CandidatePage,
|
|
CaseCreate,
|
|
CaseOut,
|
|
FunnelOut,
|
|
JobOut,
|
|
ProvenanceOut,
|
|
ReportOut,
|
|
ScoreOut,
|
|
)
|
|
from app.services import candidates as case_view
|
|
from app.services import events, triage
|
|
from app.services.scoring import score_job
|
|
|
|
logger = logging.getLogger(__name__)
|
|
router = APIRouter()
|
|
|
|
REPORT_TOP = 5
|
|
|
|
|
|
async def _case_or_404(session: SessionDep, case_id: uuid.UUID) -> Case:
|
|
case = await case_view.get_case(session, case_id)
|
|
if case is None:
|
|
raise HTTPException(404, "case not found")
|
|
return case
|
|
|
|
|
|
async def _shortlisted_counts(session: SessionDep, case_ids: list[uuid.UUID]) -> dict[uuid.UUID, int]:
|
|
if not case_ids:
|
|
return {}
|
|
rows = await session.execute(
|
|
select(Job.case_id, func.count(VariantDecision.id))
|
|
.join(Variant, Variant.job_id == Job.id)
|
|
.join(VariantDecision, VariantDecision.variant_id == Variant.id)
|
|
.where(Job.case_id.in_(case_ids), VariantDecision.state == DecisionState.shortlisted)
|
|
.group_by(Job.case_id)
|
|
)
|
|
return dict(rows.all()) # type: ignore[arg-type]
|
|
|
|
|
|
async def _latest_jobs(session: SessionDep, case_ids: list[uuid.UUID]) -> dict[uuid.UUID, Job]:
|
|
if not case_ids:
|
|
return {}
|
|
jobs = await session.scalars(
|
|
select(Job).where(Job.case_id.in_(case_ids)).order_by(Job.created_at.desc())
|
|
)
|
|
latest: dict[uuid.UUID, Job] = {}
|
|
for job in jobs: # ordered newest first, so the first one wins
|
|
latest.setdefault(job.case_id, job)
|
|
return latest
|
|
|
|
|
|
def _as_case_out(case: Case, job: Job | None, shortlisted: int) -> CaseOut:
|
|
out = CaseOut.model_validate(case)
|
|
out.latest_job = JobOut.model_validate(job) if job is not None else None
|
|
out.shortlisted = shortlisted
|
|
return out
|
|
|
|
|
|
@router.get("", response_model=list[CaseOut])
|
|
async def list_cases(session: SessionDep):
|
|
cases = (
|
|
await session.scalars(
|
|
select(Case).order_by(Case.created_at.desc()).options(selectinload(Case.phenotypes))
|
|
)
|
|
).all()
|
|
ids = [c.id for c in cases]
|
|
jobs, counts = await _latest_jobs(session, ids), await _shortlisted_counts(session, ids)
|
|
return [_as_case_out(c, jobs.get(c.id), counts.get(c.id, 0)) for c in cases]
|
|
|
|
|
|
@router.post("", response_model=CaseOut, status_code=status.HTTP_201_CREATED)
|
|
async def create_case(payload: CaseCreate, session: SessionDep):
|
|
case = Case(
|
|
name=payload.name,
|
|
vcf_uri=payload.vcf_uri,
|
|
assembly=payload.assembly,
|
|
phenotypes=[CasePhenotype(hpo_id=p.hpo_id, label=p.label) for p in payload.phenotypes],
|
|
)
|
|
session.add(case)
|
|
try:
|
|
await session.commit()
|
|
except IntegrityError: # cases.name is unique
|
|
await session.rollback()
|
|
raise HTTPException(409, f"a case named {payload.name!r} already exists") from None
|
|
await session.refresh(case, attribute_names=["phenotypes"])
|
|
return _as_case_out(case, None, 0)
|
|
|
|
|
|
@router.get("/{case_id}", response_model=CaseOut)
|
|
async def get_case(case_id: uuid.UUID, session: SessionDep):
|
|
case = await _case_or_404(session, case_id)
|
|
counts = await _shortlisted_counts(session, [case_id])
|
|
return _as_case_out(case, await case_view.latest_job(session, case_id), counts.get(case_id, 0))
|
|
|
|
|
|
@router.get("/{case_id}/jobs", response_model=list[JobOut])
|
|
async def list_jobs(case_id: uuid.UUID, session: SessionDep):
|
|
result = await session.scalars(
|
|
select(Job).where(Job.case_id == case_id).order_by(Job.created_at.desc())
|
|
)
|
|
return result.all()
|
|
|
|
|
|
@router.post("/{case_id}/annotate", response_model=JobOut, status_code=status.HTTP_202_ACCEPTED)
|
|
async def annotate(case_id: uuid.UUID, session: SessionDep):
|
|
case = await _case_or_404(session, case_id)
|
|
# Commit `running` before launching: a local run that dies instantly is marked failed by its
|
|
# watcher, and a later status write here would overwrite that.
|
|
job = Job(case_id=case.id, status=JobStatus.running)
|
|
session.add(job)
|
|
await session.commit()
|
|
try:
|
|
job.workflow_ref = await events.launch(job.id, case.vcf_uri, case.assembly)
|
|
except events.LaunchError as e:
|
|
job.status = JobStatus.failed
|
|
job.log = str(e)
|
|
job.finished_at = datetime.now(UTC)
|
|
await session.commit()
|
|
await session.refresh(job)
|
|
return job
|
|
|
|
|
|
@router.post("/{case_id}/score", response_model=ScoreOut)
|
|
async def score(case_id: uuid.UUID, session: SessionDep):
|
|
await _case_or_404(session, case_id)
|
|
job = await case_view.latest_job(session, case_id, status=JobStatus.succeeded)
|
|
if job is None:
|
|
raise HTTPException(409, "no finished annotation to score")
|
|
try:
|
|
scored, version = await score_job(job.id, session)
|
|
except Exception as e:
|
|
# No registry, no model behind the alias, a model that will not load: all of these are
|
|
# the environment being unready, not a bug in the request. Name what is missing and keep
|
|
# the exception in the log, where it is useful, rather than in the UI, where it is noise.
|
|
logger.exception("scoring case %s failed", case_id)
|
|
raise HTTPException(
|
|
503,
|
|
f"no model available: {settings.model_name}@{settings.model_alias} "
|
|
f"via {settings.mlflow_tracking_uri}",
|
|
) from e
|
|
return ScoreOut(case_id=case_id, scored=scored, model_version=version)
|
|
|
|
|
|
@router.get("/{case_id}/candidates", response_model=CandidatePage)
|
|
async def list_candidates(
|
|
case_id: uuid.UUID,
|
|
session: SessionDep,
|
|
gene: str | None = None,
|
|
impact: str | None = Query(None, pattern="^(HIGH|MODERATE|LOW|MODIFIER)$"),
|
|
max_af: float | None = Query(None, ge=0, le=1),
|
|
state: str | None = Query(None, pattern="^(shortlisted|dismissed|undecided)$"),
|
|
limit: int = Query(50, ge=1, le=500),
|
|
offset: int = Query(0, ge=0),
|
|
) -> CandidatePage:
|
|
case = await _case_or_404(session, case_id)
|
|
view = await case_view.build(session, case)
|
|
|
|
items = view.candidates
|
|
if gene:
|
|
items = [c for c in items if (c.variant.gene or "").upper() == gene.upper()]
|
|
if impact:
|
|
items = [c for c in items if c.variant.impact == impact]
|
|
if max_af is not None:
|
|
items = [c for c in items if c.variant.gnomad_af is None or c.variant.gnomad_af <= max_af]
|
|
if state == "undecided":
|
|
items = [c for c in items if c.variant.decision is None]
|
|
elif state is not None:
|
|
items = [c for c in items if c.variant.decision and c.variant.decision.state.value == state]
|
|
|
|
labels = view.labels
|
|
return CandidatePage(
|
|
# The funnel describes the whole case, not the filtered view.
|
|
funnel=FunnelOut(**asdict(view.funnel)),
|
|
weights=triage.WEIGHTS,
|
|
items=[CandidateOut.from_candidate(c, labels) for c in items[offset : offset + limit]],
|
|
total=len(items),
|
|
limit=limit,
|
|
offset=offset,
|
|
)
|
|
|
|
|
|
@router.get("/{case_id}/report", response_model=ReportOut)
|
|
async def report(case_id: uuid.UUID, session: SessionDep) -> ReportOut:
|
|
case = await _case_or_404(session, case_id)
|
|
view = await case_view.build(session, case)
|
|
labels = view.labels
|
|
|
|
def decided(state: DecisionState) -> list[CandidateOut]:
|
|
return [
|
|
CandidateOut.from_candidate(c, labels)
|
|
for c in view.candidates
|
|
if c.variant.decision is not None and c.variant.decision.state == state
|
|
]
|
|
|
|
shortlisted, dismissed = decided(DecisionState.shortlisted), decided(DecisionState.dismissed)
|
|
top = [
|
|
CandidateOut.from_candidate(c, labels)
|
|
for c in view.candidates
|
|
if c.variant.decision is None
|
|
][:REPORT_TOP]
|
|
prediction = next((c.variant.prediction for c in view.candidates if c.variant.prediction), None)
|
|
return ReportOut(
|
|
case=_as_case_out(case, view.job, len(shortlisted)),
|
|
funnel=FunnelOut(**asdict(view.funnel)),
|
|
generated_at=datetime.now(UTC),
|
|
provenance=ProvenanceOut(
|
|
job_id=view.job.id if view.job else None,
|
|
vep_version=view.job.vep_version if view.job else None,
|
|
finished_at=view.job.finished_at if view.job else None,
|
|
model_name=prediction.model_name if prediction else None,
|
|
model_version=prediction.model_version if prediction else None,
|
|
),
|
|
shortlisted=shortlisted,
|
|
dismissed=dismissed,
|
|
top=top,
|
|
)
|