Makes a real annotation runnable locally without the 25 GB VEP cache, which is what
the demo needs and what a reviewer can reproduce in minutes.
- params.vep_database (VEP_DATABASE=true) queries Ensembl's public database instead of
a local cache. Slower per variant and fewer fields, so --everything is swapped for the
flags the loader actually stores. Its cache placeholder is NO_CACHE, not NO_FILE:
Nextflow rejects two staged inputs sharing a filename.
- PIPELINE_DATABASE_URL is handed to the pipeline when set. The loader runs inside a
container, where the API's own localhost URL would point at the container itself.
- README: how to run the UI's annotate button locally against host Nextflow + Docker.
Verified end to end on pipeline/tests/data/tiny.vcf: bcftools norm split the multiallelic
record, VEP 113 annotated 4 variants live, the loader wrote them and marked the job
succeeded, and the UI shows them. The deletion came back as 22:42126611 CT>C with exact
VCF alleles, which is the case the audit's ID-tagging fix exists for.
Tests: api 51, loader 16, stub run 3/3; ruff, mypy clean.
An end-to-end audit found the repo could not build, test or run as shipped. This
fixes every finding, then adds a Cloud Run track so the demo costs about £1/month
idle instead of ~£150.
CI (red on its first run)
- api: setuptools could not build the package (flat layout with app/ and alembic/)
- web: missing @types/node; `vitest run` exited 1 with no test files
- pipeline: the stub run needed a gitignored VCF, and no process had a stub block
- ruff pinned, mypy configured, DB tests on real Postgres (pgserver locally, service in CI)
ML serving (scores were meaningless)
- the registered model now carries its own feature engineering and returns predict_proba,
so serving sends raw columns and cannot drift from training
- resolve by registry alias (stages are deprecated in MLflow 3) and record the real
version; re-scoring upserts instead of failing on the unique constraint
- ClinVar labels parsed from VEP's lowercase terms
Pipeline
- exact ref/alt recovered from a CHROM_POS_REF_ALT VCF ID; loading is idempotent
- job status reaches running/failed/succeeded, so the UI stops polling dead jobs
- DATABASE_URL travels in the environment or a Nextflow secret, never on a command line
- VEP cache and plugins staged as inputs; the gcp profile runs tasks on Google Batch
Deployment
- the API serves /api (matching the ingress); the web app reads its API URL at runtime
- migrations run in an init container under a Postgres advisory lock
- terraform: custom VPC shared with Batch, private Cloud SQL, API enablement, Workload
Identity bindings, Secret Manager, deletion protection
- serverless track, now the default: Cloud Run services scaling to zero, a Cloud Run job
for the Nextflow driver, and Neon or Cloud SQL behind one DATABASE_URL secret. GKE and
Argo remain, behind -var deploy_kubernetes=true. See docs/cloud.md.
Correctness and security
- 409 on duplicate sample names, 422 on bad paging, natural chromosome ordering, wider
VEP text columns, enum dropped on downgrade, the sample's assembly actually used
- vcf_uri restricted to gs:// objects or files under the data root, blocking option injection
- CORS restricted to configured origins; `make down` no longer deletes volumes
Data
- docs/data.md records the peer-reviewed, openly licensed sources (GIAB HG002, ClinVar,
gnomAD) with citations and an honest evaluation plan; `make data` fetches a chr22 slice
Verified: api 50 tests, ml 18, loader 16, web 12; ruff, mypy, svelte-check, terraform
validate and both kustomize overlays clean.
Kemal Yaylali