commit 5463f489a343e720f533a2fb3b68b059268580ba Author: Kemal Yaylali Date: Fri Sep 11 16:55:35 2026 +0100 Initial release: rarelens platform skeleton (AGPL-3.0) End-to-end variant interpretation platform for rare genetic disease research: SvelteKit UI, FastAPI + PostgreSQL API, Nextflow/Ensembl VEP pipeline, LightGBM pathogenicity scoring with MLflow, K8s/ArgoCD/GCP infrastructure. Public test data only; no clinical claims. diff --git a/.github/workflows/ci.yml b/.github/workflows/ci.yml new file mode 100644 index 0000000..3f61fe0 --- /dev/null +++ b/.github/workflows/ci.yml @@ -0,0 +1,64 @@ +name: ci +on: + pull_request: + push: + branches: [main] + +jobs: + api: + runs-on: ubuntu-latest + services: + postgres: + image: postgres:16-alpine + env: { POSTGRES_USER: rarelens, POSTGRES_PASSWORD: rarelens, POSTGRES_DB: rarelens } + ports: ["5432:5432"] + options: --health-cmd "pg_isready -U rarelens" --health-interval 5s --health-retries 10 + steps: + - uses: actions/checkout@v4 + - uses: astral-sh/setup-uv@v3 + - run: uv pip install --system -e "api[dev]" + - run: cd api && ruff check . && mypy app + - run: cd api && pytest -q + env: { DATABASE_URL: postgresql+asyncpg://rarelens:rarelens@localhost:5432/rarelens } + + web: + runs-on: ubuntu-latest + steps: + - uses: actions/checkout@v4 + - uses: actions/setup-node@v4 + with: { node-version: 22, cache: npm, cache-dependency-path: web/package-lock.json } + - run: cd web && npm ci && npm run check && npm test && npm run build + + pipeline: + runs-on: ubuntu-latest + steps: + - uses: actions/checkout@v4 + - uses: nf-core/setup-nextflow@v2 + - run: cd pipeline && nextflow run main.nf -profile docker --vcf ../data/example.vcf.gz -stub-run + + terraform: + runs-on: ubuntu-latest + steps: + - uses: actions/checkout@v4 + - uses: hashicorp/setup-terraform@v3 + - run: cd infra/terraform && terraform init -backend=false && terraform fmt -check && terraform validate + + images: + if: github.ref == 'refs/heads/main' + needs: [api, web, pipeline] + runs-on: ubuntu-latest + permissions: { contents: read, id-token: write } + strategy: + matrix: { component: [api, web, pipeline, ml] } + steps: + - uses: actions/checkout@v4 + - uses: google-github-actions/auth@v2 + with: + workload_identity_provider: ${{ secrets.GCP_WIF_PROVIDER }} + service_account: ${{ secrets.GCP_CI_SA }} + - run: gcloud auth configure-docker europe-west2-docker.pkg.dev --quiet + - uses: docker/build-push-action@v6 + with: + context: ${{ matrix.component }} + push: true + tags: europe-west2-docker.pkg.dev/${{ secrets.GCP_PROJECT }}/rarelens/${{ matrix.component }}:${{ github.sha }} diff --git a/.github/workflows/deploy.yml b/.github/workflows/deploy.yml new file mode 100644 index 0000000..fae4c9b --- /dev/null +++ b/.github/workflows/deploy.yml @@ -0,0 +1,22 @@ +# GitOps: CI only bumps image tags in the gcp overlay; ArgoCD does the deploy. +name: bump-images +on: + workflow_run: + workflows: [ci] + types: [completed] + branches: [main] + +jobs: + bump: + if: ${{ github.event.workflow_run.conclusion == 'success' }} + runs-on: ubuntu-latest + steps: + - uses: actions/checkout@v4 + - uses: imranismail/setup-kustomize@v2 + - run: | + cd infra/k8s/overlays/gcp + for c in api web; do + kustomize edit set image rarelens/$c=europe-west2-docker.pkg.dev/${{ secrets.GCP_PROJECT }}/rarelens/$c:${{ github.event.workflow_run.head_sha }} + done + - uses: stefanzweifel/git-auto-commit-action@v5 + with: { commit_message: "chore: bump images to ${{ github.event.workflow_run.head_sha }}" } diff --git a/.gitignore b/.gitignore new file mode 100644 index 0000000..7c226ad --- /dev/null +++ b/.gitignore @@ -0,0 +1,17 @@ +__pycache__/ +*.pyc +.venv/ +.env +!web/.env +node_modules/ +web/.svelte-kit/ +web/build/ +pipeline/work/ +pipeline/.nextflow* +pipeline/results/ +mlruns/ +*.tfstate +*.tfstate.backup +.terraform/ +data/*.vcf* +!data/README.md diff --git a/LICENSE b/LICENSE new file mode 100644 index 0000000..be3f7b2 --- /dev/null +++ b/LICENSE @@ -0,0 +1,661 @@ + GNU AFFERO GENERAL PUBLIC LICENSE + Version 3, 19 November 2007 + + Copyright (C) 2007 Free Software Foundation, Inc. + Everyone is permitted to copy and distribute verbatim copies + of this license document, but changing it is not allowed. + + Preamble + + The GNU Affero General Public License is a free, copyleft license for +software and other kinds of works, specifically designed to ensure +cooperation with the community in the case of network server software. + + The licenses for most software and other practical works are designed +to take away your freedom to share and change the works. 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It is safest +to attach them to the start of each source file to most effectively +state the exclusion of warranty; and each file should have at least +the "copyright" line and a pointer to where the full notice is found. + + + Copyright (C) + + This program is free software: you can redistribute it and/or modify + it under the terms of the GNU Affero General Public License as published by + the Free Software Foundation, either version 3 of the License, or + (at your option) any later version. + + This program is distributed in the hope that it will be useful, + but WITHOUT ANY WARRANTY; without even the implied warranty of + MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the + GNU Affero General Public License for more details. + + You should have received a copy of the GNU Affero General Public License + along with this program. If not, see . + +Also add information on how to contact you by electronic and paper mail. + + If your software can interact with users remotely through a computer +network, you should also make sure that it provides a way for users to +get its source. For example, if your program is a web application, its +interface could display a "Source" link that leads users to an archive +of the code. There are many ways you could offer source, and different +solutions will be better for different programs; see section 13 for the +specific requirements. + + You should also get your employer (if you work as a programmer) or school, +if any, to sign a "copyright disclaimer" for the program, if necessary. +For more information on this, and how to apply and follow the GNU AGPL, see +. diff --git a/Makefile b/Makefile new file mode 100644 index 0000000..dba90b6 --- /dev/null +++ b/Makefile @@ -0,0 +1,25 @@ +.PHONY: up down migrate test pipeline kind lint + +up: + docker compose up -d --build + +down: + docker compose down -v + +migrate: + docker compose exec api alembic upgrade head + +test: + cd api && uv run pytest -q + cd web && npm test + +lint: + cd api && uv run ruff check . && uv run mypy app + cd web && npm run check + +pipeline: + cd pipeline && nextflow run main.nf -profile docker --vcf ../data/example.vcf.gz --outdir results + +kind: + kind create cluster --name rarelens || true + kubectl apply -k infra/k8s/overlays/local diff --git a/README.md b/README.md new file mode 100644 index 0000000..8f0198d --- /dev/null +++ b/README.md @@ -0,0 +1,54 @@ +# rarelens + +A small, end-to-end variant interpretation platform for rare genetic disease research. +Scientists upload a VCF, a Nextflow workflow annotates it with Ensembl VEP, a machine +learning model scores each variant, and results are browsable in a web app. + +This repository is a **self-training lab**. It exists so that one engineer can learn, in +public, how a modern life-sciences platform is built end to end: full-stack application, +scientific pipeline, ML serving, and cloud infrastructure, all in one monorepo. It is not a +clinical tool and makes no diagnostic claims. + +## What is in the box + +| Layer | Technology | Directory | +|------------|--------------------------------------------------------|----------------------| +| Pipeline | Nextflow DSL2, bcftools, Ensembl VEP, Docker | `pipeline/` | +| API | FastAPI, Pydantic v2, SQLAlchemy 2.0 (async), Alembic | `api/` | +| Database | PostgreSQL 16 | `docker-compose.yml` | +| Frontend | SvelteKit, TypeScript | `web/` | +| ML | LightGBM pathogenicity scorer, MLflow tracking | `ml/` | +| Orchestration | Argo Workflows (pipeline), Pub/Sub (events) | `infra/argo-workflows/` | +| Platform | Kubernetes (Kustomize), ArgoCD (GitOps) | `infra/k8s/`, `infra/argocd/` | +| Cloud | GCP: GKE Autopilot, Cloud SQL, GCS, Artifact Registry | `infra/terraform/` | +| CI/CD | GitHub Actions, Workload Identity Federation | `.github/workflows/` | + +## Quick start (local) + +```bash +make up # postgres + api + web via docker-compose +make migrate # alembic upgrade head +make pipeline # nextflow run pipeline/main.nf -profile docker --vcf data/example.vcf.gz +make kind # spin up a local kind cluster and apply infra/k8s/overlays/local +``` + +Then open http://localhost:5173. + +## Architecture + +See [docs/architecture.md](docs/architecture.md) for the diagram and the reasoning behind +each choice. + +## Status + +Work in progress. Milestones, in order: + +1. Skeleton, Postgres, FastAPI, Nextflow VEP annotation on a public VCF, CI green +2. SvelteKit UI: sample list, variant table with filters, job status +3. Kubernetes manifests, kind, Argo Workflows trigger +4. Terraform for GCP, ArgoCD GitOps deploy +5. Pathogenicity model, MLflow registry, prediction endpoint + +## Licence + +AGPL-3.0. Test data are public (ClinVar, gnomAD subsets); no patient data are used or accepted. diff --git a/api/Dockerfile b/api/Dockerfile new file mode 100644 index 0000000..58161d7 --- /dev/null +++ b/api/Dockerfile @@ -0,0 +1,8 @@ +FROM python:3.12-slim +WORKDIR /app +RUN pip install --no-cache-dir uv +COPY pyproject.toml . +RUN uv pip install --system -e . +COPY . . +EXPOSE 8000 +CMD ["uvicorn", "app.main:app", "--host", "0.0.0.0", "--port", "8000"] diff --git a/api/alembic.ini b/api/alembic.ini new file mode 100644 index 0000000..8a9810c --- /dev/null +++ b/api/alembic.ini @@ -0,0 +1,36 @@ +[alembic] +script_location = alembic +sqlalchemy.url = postgresql+asyncpg://rarelens:rarelens@db:5432/rarelens + +[loggers] +keys = root,sqlalchemy,alembic + +[handlers] +keys = console + +[formatters] +keys = generic + +[logger_root] +level = WARN +handlers = console + +[logger_sqlalchemy] +level = WARN +handlers = +qualname = sqlalchemy.engine + +[logger_alembic] +level = INFO +handlers = +qualname = alembic + +[handler_console] +class = StreamHandler +args = (sys.stderr,) +level = NOTSET +formatter = generic + +[formatter_generic] +format = %(levelname)-5.5s [%(name)s] %(message)s +datefmt = %H:%M:%S diff --git a/api/alembic/env.py b/api/alembic/env.py new file mode 100644 index 0000000..1c58b11 --- /dev/null +++ b/api/alembic/env.py @@ -0,0 +1,32 @@ +import asyncio +from logging.config import fileConfig + +from alembic import context +from sqlalchemy.ext.asyncio import async_engine_from_config +from sqlalchemy import pool + +from app.config import settings +from app.models import Base + +config = context.config +config.set_main_option("sqlalchemy.url", settings.database_url) +if config.config_file_name: + fileConfig(config.config_file_name) +target_metadata = Base.metadata + + +def run_migrations(connection): + context.configure(connection=connection, target_metadata=target_metadata) + with context.begin_transaction(): + context.run_migrations() + + +async def run_async(): + engine = async_engine_from_config( + config.get_section(config.config_ini_section, {}), poolclass=pool.NullPool + ) + async with engine.connect() as conn: + await conn.run_sync(run_migrations) + + +asyncio.run(run_async()) diff --git a/api/alembic/script.py.mako b/api/alembic/script.py.mako new file mode 100644 index 0000000..3cf5352 --- /dev/null +++ b/api/alembic/script.py.mako @@ -0,0 +1,26 @@ +"""${message} + +Revision ID: ${up_revision} +Revises: ${down_revision | comma,n} +Create Date: ${create_date} + +""" +from typing import Sequence, Union + +from alembic import op +import sqlalchemy as sa +${imports if imports else ""} + +# revision identifiers, used by Alembic. +revision: str = ${repr(up_revision)} +down_revision: Union[str, None] = ${repr(down_revision)} +branch_labels: Union[str, Sequence[str], None] = ${repr(branch_labels)} +depends_on: Union[str, Sequence[str], None] = ${repr(depends_on)} + + +def upgrade() -> None: + ${upgrades if upgrades else "pass"} + + +def downgrade() -> None: + ${downgrades if downgrades else "pass"} \ No newline at end of file diff --git a/api/alembic/versions/a3e9ead256a5_initial_schema.py b/api/alembic/versions/a3e9ead256a5_initial_schema.py new file mode 100644 index 0000000..19e8f55 --- /dev/null +++ b/api/alembic/versions/a3e9ead256a5_initial_schema.py @@ -0,0 +1,90 @@ +"""initial schema + +Revision ID: a3e9ead256a5 +Revises: +Create Date: 2026-09-11 15:36:04.335440 + +""" +from typing import Sequence, Union + +from alembic import op +import sqlalchemy as sa +from sqlalchemy.dialects import postgresql + +# revision identifiers, used by Alembic. +revision: str = 'a3e9ead256a5' +down_revision: Union[str, None] = None +branch_labels: Union[str, Sequence[str], None] = None +depends_on: Union[str, Sequence[str], None] = None + + +def upgrade() -> None: + # ### commands auto generated by Alembic - please adjust! ### + op.create_table('samples', + sa.Column('id', sa.UUID(), nullable=False), + sa.Column('name', sa.String(length=120), nullable=False), + sa.Column('vcf_uri', sa.Text(), nullable=False), + sa.Column('assembly', sa.String(length=10), nullable=False), + sa.Column('created_at', sa.DateTime(timezone=True), server_default=sa.text('now()'), nullable=False), + sa.PrimaryKeyConstraint('id'), + sa.UniqueConstraint('name') + ) + op.create_table('jobs', + sa.Column('id', sa.UUID(), nullable=False), + sa.Column('sample_id', sa.UUID(), nullable=False), + sa.Column('status', sa.Enum('queued', 'running', 'succeeded', 'failed', name='jobstatus'), nullable=False), + sa.Column('workflow_ref', sa.String(length=200), nullable=True), + sa.Column('vep_version', sa.String(length=40), nullable=True), + sa.Column('log', sa.Text(), nullable=True), + sa.Column('created_at', sa.DateTime(timezone=True), server_default=sa.text('now()'), nullable=False), + sa.Column('finished_at', sa.DateTime(timezone=True), nullable=True), + sa.ForeignKeyConstraint(['sample_id'], ['samples.id'], ondelete='CASCADE'), + sa.PrimaryKeyConstraint('id') + ) + op.create_table('variants', + sa.Column('id', sa.Integer(), autoincrement=True, nullable=False), + sa.Column('job_id', sa.UUID(), nullable=False), + sa.Column('chrom', sa.String(length=10), nullable=False), + sa.Column('pos', sa.Integer(), nullable=False), + sa.Column('ref', sa.Text(), nullable=False), + sa.Column('alt', sa.Text(), nullable=False), + sa.Column('gene', sa.String(length=60), nullable=True), + sa.Column('consequence', sa.String(length=120), nullable=True), + sa.Column('impact', sa.String(length=20), nullable=True), + sa.Column('hgvsc', sa.Text(), nullable=True), + sa.Column('hgvsp', sa.Text(), nullable=True), + sa.Column('gnomad_af', sa.Float(), nullable=True), + sa.Column('clinvar_sig', sa.String(length=120), nullable=True), + sa.Column('annotations', postgresql.JSONB(astext_type=sa.Text()), nullable=False), + sa.ForeignKeyConstraint(['job_id'], ['jobs.id'], ondelete='CASCADE'), + sa.PrimaryKeyConstraint('id') + ) + op.create_index(op.f('ix_variants_chrom'), 'variants', ['chrom'], unique=False) + op.create_index(op.f('ix_variants_gene'), 'variants', ['gene'], unique=False) + op.create_index(op.f('ix_variants_job_id'), 'variants', ['job_id'], unique=False) + op.create_index(op.f('ix_variants_pos'), 'variants', ['pos'], unique=False) + op.create_table('predictions', + sa.Column('id', sa.Integer(), autoincrement=True, nullable=False), + sa.Column('variant_id', sa.Integer(), nullable=False), + sa.Column('model_name', sa.String(length=80), nullable=False), + sa.Column('model_version', sa.String(length=40), nullable=False), + sa.Column('score', sa.Float(), nullable=False), + sa.Column('created_at', sa.DateTime(timezone=True), server_default=sa.text('now()'), nullable=False), + sa.ForeignKeyConstraint(['variant_id'], ['variants.id'], ondelete='CASCADE'), + sa.PrimaryKeyConstraint('id'), + sa.UniqueConstraint('variant_id') + ) + # ### end Alembic commands ### + + +def downgrade() -> None: + # ### commands auto generated by Alembic - please adjust! ### + op.drop_table('predictions') + op.drop_index(op.f('ix_variants_pos'), table_name='variants') + op.drop_index(op.f('ix_variants_job_id'), table_name='variants') + op.drop_index(op.f('ix_variants_gene'), table_name='variants') + op.drop_index(op.f('ix_variants_chrom'), table_name='variants') + op.drop_table('variants') + op.drop_table('jobs') + op.drop_table('samples') + # ### end Alembic commands ### \ No newline at end of file diff --git a/api/app/__init__.py b/api/app/__init__.py new file mode 100644 index 0000000..e69de29 diff --git a/api/app/config.py b/api/app/config.py new file mode 100644 index 0000000..02d09b9 --- /dev/null +++ b/api/app/config.py @@ -0,0 +1,15 @@ +from pydantic_settings import BaseSettings, SettingsConfigDict + + +class Settings(BaseSettings): + model_config = SettingsConfigDict(env_file=".env", extra="ignore") + + database_url: str = "postgresql+asyncpg://rarelens:rarelens@localhost:5432/rarelens" + mlflow_tracking_uri: str = "http://localhost:5000" + model_name: str = "rarelens-pathogenicity" + model_stage: str = "Production" + gcs_bucket: str | None = None # set in GCP; local uses ./data + pubsub_topic: str | None = None # "vcf-uploaded" in GCP; local runs pipeline inline + + +settings = Settings() diff --git a/api/app/db.py b/api/app/db.py new file mode 100644 index 0000000..db06307 --- /dev/null +++ b/api/app/db.py @@ -0,0 +1,13 @@ +from collections.abc import AsyncIterator + +from sqlalchemy.ext.asyncio import AsyncSession, async_sessionmaker, create_async_engine + +from app.config import settings + +engine = create_async_engine(settings.database_url, pool_pre_ping=True) +SessionLocal = async_sessionmaker(engine, expire_on_commit=False) + + +async def get_session() -> AsyncIterator[AsyncSession]: + async with SessionLocal() as session: + yield session diff --git a/api/app/main.py b/api/app/main.py new file mode 100644 index 0000000..b4468d1 --- /dev/null +++ b/api/app/main.py @@ -0,0 +1,28 @@ +from contextlib import asynccontextmanager + +from fastapi import FastAPI +from fastapi.middleware.cors import CORSMiddleware + +from app.routers import jobs, predictions, samples, variants + + +@asynccontextmanager +async def lifespan(app: FastAPI): + # Warm the model cache here once ml/ is wired in. + yield + + +app = FastAPI(title="rarelens API", version="0.1.0", lifespan=lifespan) +app.add_middleware( + CORSMiddleware, allow_origins=["*"], allow_methods=["*"], allow_headers=["*"] +) + +app.include_router(samples.router, prefix="/samples", tags=["samples"]) +app.include_router(jobs.router, prefix="/jobs", tags=["jobs"]) +app.include_router(variants.router, prefix="/variants", tags=["variants"]) +app.include_router(predictions.router, prefix="/predictions", tags=["predictions"]) + + +@app.get("/health", tags=["ops"]) +async def health() -> dict[str, str]: + return {"status": "ok"} diff --git a/api/app/models.py b/api/app/models.py new file mode 100644 index 0000000..ad42308 --- /dev/null +++ b/api/app/models.py @@ -0,0 +1,77 @@ +"""SQLAlchemy 2.0 declarative models. + +One sample -> many jobs; one job -> many variants; one variant -> one prediction (latest). +""" +from datetime import datetime +import enum +import uuid + +from sqlalchemy import DateTime, Enum, Float, ForeignKey, Integer, String, Text, func +from sqlalchemy.dialects.postgresql import JSONB, UUID +from sqlalchemy.orm import DeclarativeBase, Mapped, mapped_column, relationship + + +class Base(DeclarativeBase): + pass + + +class JobStatus(str, enum.Enum): + queued = "queued" + running = "running" + succeeded = "succeeded" + failed = "failed" + + +class Sample(Base): + __tablename__ = "samples" + id: Mapped[uuid.UUID] = mapped_column(UUID(as_uuid=True), primary_key=True, default=uuid.uuid4) + name: Mapped[str] = mapped_column(String(120), unique=True) + vcf_uri: Mapped[str] = mapped_column(Text) + assembly: Mapped[str] = mapped_column(String(10), default="GRCh38") + created_at: Mapped[datetime] = mapped_column(DateTime(timezone=True), server_default=func.now()) + jobs: Mapped[list["Job"]] = relationship(back_populates="sample") + + +class Job(Base): + __tablename__ = "jobs" + id: Mapped[uuid.UUID] = mapped_column(UUID(as_uuid=True), primary_key=True, default=uuid.uuid4) + sample_id: Mapped[uuid.UUID] = mapped_column(ForeignKey("samples.id", ondelete="CASCADE")) + status: Mapped[JobStatus] = mapped_column(Enum(JobStatus), default=JobStatus.queued) + workflow_ref: Mapped[str | None] = mapped_column(String(200)) # Argo workflow name / nf run id + vep_version: Mapped[str | None] = mapped_column(String(40)) + log: Mapped[str | None] = mapped_column(Text) + created_at: Mapped[datetime] = mapped_column(DateTime(timezone=True), server_default=func.now()) + finished_at: Mapped[datetime | None] = mapped_column(DateTime(timezone=True)) + sample: Mapped[Sample] = relationship(back_populates="jobs") + variants: Mapped[list["Variant"]] = relationship(back_populates="job") + + +class Variant(Base): + __tablename__ = "variants" + id: Mapped[int] = mapped_column(Integer, primary_key=True, autoincrement=True) + job_id: Mapped[uuid.UUID] = mapped_column(ForeignKey("jobs.id", ondelete="CASCADE"), index=True) + chrom: Mapped[str] = mapped_column(String(10), index=True) + pos: Mapped[int] = mapped_column(Integer, index=True) + ref: Mapped[str] = mapped_column(Text) + alt: Mapped[str] = mapped_column(Text) + gene: Mapped[str | None] = mapped_column(String(60), index=True) + consequence: Mapped[str | None] = mapped_column(String(120)) + impact: Mapped[str | None] = mapped_column(String(20)) + hgvsc: Mapped[str | None] = mapped_column(Text) + hgvsp: Mapped[str | None] = mapped_column(Text) + gnomad_af: Mapped[float | None] = mapped_column(Float) + clinvar_sig: Mapped[str | None] = mapped_column(String(120)) + annotations: Mapped[dict] = mapped_column(JSONB, default=dict) # full VEP CSQ record + job: Mapped[Job] = relationship(back_populates="variants") + prediction: Mapped["Prediction | None"] = relationship(back_populates="variant", uselist=False) + + +class Prediction(Base): + __tablename__ = "predictions" + id: Mapped[int] = mapped_column(Integer, primary_key=True, autoincrement=True) + variant_id: Mapped[int] = mapped_column(ForeignKey("variants.id", ondelete="CASCADE"), unique=True) + model_name: Mapped[str] = mapped_column(String(80)) + model_version: Mapped[str] = mapped_column(String(40)) + score: Mapped[float] = mapped_column(Float) # P(pathogenic) + created_at: Mapped[datetime] = mapped_column(DateTime(timezone=True), server_default=func.now()) + variant: Mapped[Variant] = relationship(back_populates="prediction") diff --git a/api/app/routers/__init__.py b/api/app/routers/__init__.py new file mode 100644 index 0000000..e69de29 diff --git a/api/app/routers/jobs.py b/api/app/routers/jobs.py new file mode 100644 index 0000000..2769b4b --- /dev/null +++ b/api/app/routers/jobs.py @@ -0,0 +1,18 @@ +import uuid + +from fastapi import APIRouter, Depends, HTTPException +from sqlalchemy.ext.asyncio import AsyncSession + +from app.db import get_session +from app.models import Job +from app.schemas import JobOut + +router = APIRouter() + + +@router.get("/{job_id}", response_model=JobOut) +async def get_job(job_id: uuid.UUID, session: AsyncSession = Depends(get_session)): + job = await session.get(Job, job_id) + if job is None: + raise HTTPException(404, "job not found") + return job diff --git a/api/app/routers/predictions.py b/api/app/routers/predictions.py new file mode 100644 index 0000000..d3f7e93 --- /dev/null +++ b/api/app/routers/predictions.py @@ -0,0 +1,16 @@ +import uuid + +from fastapi import APIRouter, Depends +from sqlalchemy.ext.asyncio import AsyncSession + +from app.db import get_session +from app.services.scoring import score_job + +router = APIRouter() + + +@router.post("/score/{job_id}") +async def score(job_id: uuid.UUID, session: AsyncSession = Depends(get_session)) -> dict: + """Load the registered MLflow model and score every variant of a job.""" + n = await score_job(job_id, session) + return {"job_id": str(job_id), "scored": n} diff --git a/api/app/routers/samples.py b/api/app/routers/samples.py new file mode 100644 index 0000000..7b64f56 --- /dev/null +++ b/api/app/routers/samples.py @@ -0,0 +1,49 @@ +import uuid + +from fastapi import APIRouter, Depends, HTTPException, status +from sqlalchemy import select +from sqlalchemy.ext.asyncio import AsyncSession + +from app.db import get_session +from app.models import Job, Sample +from app.schemas import JobOut, SampleCreate, SampleOut +from app.services.events import publish_vcf_uploaded + +router = APIRouter() + + +@router.get("", response_model=list[SampleOut]) +async def list_samples(session: AsyncSession = Depends(get_session)): + result = await session.scalars(select(Sample).order_by(Sample.created_at.desc())) + return result.all() + + +@router.post("", response_model=SampleOut, status_code=status.HTTP_201_CREATED) +async def create_sample(payload: SampleCreate, session: AsyncSession = Depends(get_session)): + sample = Sample(**payload.model_dump()) + session.add(sample) + await session.commit() + await session.refresh(sample) + return sample + + +@router.get("/{sample_id}/jobs", response_model=list[JobOut]) +async def list_jobs(sample_id: uuid.UUID, session: AsyncSession = Depends(get_session)): + result = await session.scalars( + select(Job).where(Job.sample_id == sample_id).order_by(Job.created_at.desc()) + ) + return result.all() + + +@router.post("/{sample_id}/annotate", response_model=JobOut, status_code=status.HTTP_202_ACCEPTED) +async def annotate(sample_id: uuid.UUID, session: AsyncSession = Depends(get_session)): + sample = await session.get(Sample, sample_id) + if sample is None: + raise HTTPException(404, "sample not found") + job = Job(sample_id=sample.id) + session.add(job) + await session.commit() + await session.refresh(job) + # Emits to Pub/Sub in GCP; runs the Nextflow pipeline inline for local dev. + await publish_vcf_uploaded(job_id=job.id, vcf_uri=sample.vcf_uri) + return job diff --git a/api/app/routers/variants.py b/api/app/routers/variants.py new file mode 100644 index 0000000..2506efb --- /dev/null +++ b/api/app/routers/variants.py @@ -0,0 +1,43 @@ +import uuid + +from fastapi import APIRouter, Depends, Query +from sqlalchemy import func, select +from sqlalchemy.ext.asyncio import AsyncSession +from sqlalchemy.orm import selectinload + +from app.db import get_session +from app.models import Prediction, Variant +from app.schemas import VariantPage + +router = APIRouter() + + +@router.get("", response_model=VariantPage) +async def list_variants( + job_id: uuid.UUID, + gene: str | None = None, + impact: str | None = Query(None, pattern="^(HIGH|MODERATE|LOW|MODIFIER)$"), + max_af: float | None = Query(None, ge=0, le=1), + min_score: float | None = Query(None, ge=0, le=1), + limit: int = Query(50, le=500), + offset: int = 0, + session: AsyncSession = Depends(get_session), +): + stmt = select(Variant).where(Variant.job_id == job_id) + if gene: + stmt = stmt.where(Variant.gene == gene.upper()) + if impact: + stmt = stmt.where(Variant.impact == impact) + if max_af is not None: + stmt = stmt.where((Variant.gnomad_af.is_(None)) | (Variant.gnomad_af <= max_af)) + if min_score is not None: + stmt = stmt.join(Prediction, Prediction.variant_id == Variant.id).where(Prediction.score >= min_score) + + total = await session.scalar(select(func.count()).select_from(stmt.subquery())) + rows = await session.scalars( + stmt.options(selectinload(Variant.prediction)) + .order_by(Variant.chrom, Variant.pos) + .limit(limit) + .offset(offset) + ) + return VariantPage(items=rows.all(), total=total or 0, limit=limit, offset=offset) diff --git a/api/app/schemas.py b/api/app/schemas.py new file mode 100644 index 0000000..974f6a6 --- /dev/null +++ b/api/app/schemas.py @@ -0,0 +1,63 @@ +from datetime import datetime +import uuid + +from pydantic import BaseModel, ConfigDict, Field + +from app.models import JobStatus + + +class ORMModel(BaseModel): + model_config = ConfigDict(from_attributes=True) + + +class SampleCreate(BaseModel): + name: str = Field(min_length=1, max_length=120) + vcf_uri: str + assembly: str = "GRCh38" + + +class SampleOut(ORMModel): + id: uuid.UUID + name: str + vcf_uri: str + assembly: str + created_at: datetime + + +class JobOut(ORMModel): + id: uuid.UUID + sample_id: uuid.UUID + status: JobStatus + workflow_ref: str | None + vep_version: str | None + created_at: datetime + finished_at: datetime | None + + +class PredictionOut(ORMModel): + model_name: str + model_version: str + score: float + + +class VariantOut(ORMModel): + id: int + chrom: str + pos: int + ref: str + alt: str + gene: str | None + consequence: str | None + impact: str | None + hgvsc: str | None + hgvsp: str | None + gnomad_af: float | None + clinvar_sig: str | None + prediction: PredictionOut | None = None + + +class VariantPage(BaseModel): + items: list[VariantOut] + total: int + limit: int + offset: int diff --git a/api/app/services/__init__.py b/api/app/services/__init__.py new file mode 100644 index 0000000..e69de29 diff --git a/api/app/services/events.py b/api/app/services/events.py new file mode 100644 index 0000000..20856ce --- /dev/null +++ b/api/app/services/events.py @@ -0,0 +1,31 @@ +"""Event publishing. + +GCP: publish a JSON message to Pub/Sub; an Argo Events sensor turns it into an Argo Workflow. +Local: run Nextflow directly in a background task so `docker compose up` gives a working demo. +""" +import asyncio +import json +import uuid + +from app.config import settings + + +async def publish_vcf_uploaded(job_id: uuid.UUID, vcf_uri: str) -> None: + message = {"job_id": str(job_id), "vcf_uri": vcf_uri} + if settings.pubsub_topic: + from google.cloud import pubsub_v1 # optional dependency, installed in the GCP image + + publisher = pubsub_v1.PublisherClient() + publisher.publish(settings.pubsub_topic, json.dumps(message).encode()) + return + + cmd = [ + "nextflow", "run", "/pipeline/main.nf", "-profile", "docker", + "--vcf", vcf_uri, "--job_id", str(job_id), "--db_url", settings.database_url, + ] + try: + await asyncio.create_subprocess_exec(*cmd) + except FileNotFoundError: + # Nextflow is not installed in this environment (no Java toolchain yet); + # leave the job queued instead of crashing the request. + print(f"[rarelens] nextflow not found; cannot start pipeline for job {job_id}", flush=True) diff --git a/api/app/services/scoring.py b/api/app/services/scoring.py new file mode 100644 index 0000000..e0bba0e --- /dev/null +++ b/api/app/services/scoring.py @@ -0,0 +1,45 @@ +import uuid + +import mlflow +import pandas as pd +from sqlalchemy import select +from sqlalchemy.ext.asyncio import AsyncSession + +from app.config import settings +from app.models import Prediction, Variant + +_model = None + + +def load_model(): + global _model + if _model is None: + mlflow.set_tracking_uri(settings.mlflow_tracking_uri) + _model = mlflow.pyfunc.load_model(f"models:/{settings.model_name}/{settings.model_stage}") + return _model + + +def featurise(variants: list[Variant]) -> pd.DataFrame: + # Mirror ml/rarelens_ml/features.py exactly; shared package later. + return pd.DataFrame( + { + "impact": [v.impact for v in variants], + "consequence": [v.consequence for v in variants], + "gnomad_af": [v.gnomad_af if v.gnomad_af is not None else 0.0 for v in variants], + "cadd_phred": [v.annotations.get("CADD_PHRED") for v in variants], + "am_pathogenicity": [v.annotations.get("am_pathogenicity") for v in variants], + } + ) + + +async def score_job(job_id: uuid.UUID, session: AsyncSession) -> int: + variants = (await session.scalars(select(Variant).where(Variant.job_id == job_id))).all() + if not variants: + return 0 + model = load_model() + scores = model.predict(featurise(variants)) + for v, s in zip(variants, scores): + session.add(Prediction(variant_id=v.id, model_name=settings.model_name, + model_version=settings.model_stage, score=float(s))) + await session.commit() + return len(variants) diff --git a/api/pyproject.toml b/api/pyproject.toml new file mode 100644 index 0000000..c668f33 --- /dev/null +++ b/api/pyproject.toml @@ -0,0 +1,28 @@ +[project] +name = "rarelens-api" +version = "0.1.0" +description = "FastAPI backend for rarelens" +requires-python = ">=3.12" +dependencies = [ + "fastapi>=0.115", + "uvicorn[standard]>=0.30", + "sqlalchemy[asyncio]>=2.0", + "asyncpg>=0.29", + "alembic>=1.13", + "pydantic>=2.8", + "pydantic-settings>=2.4", + "httpx>=0.27", + "mlflow-skinny>=2.16", + "lightgbm>=4.5", + "pandas>=2.2", +] + +[project.optional-dependencies] +dev = ["pytest", "pytest-asyncio", "ruff", "mypy", "aiosqlite"] + +[tool.ruff] +line-length = 100 +target-version = "py312" + +[tool.pytest.ini_options] +asyncio_mode = "auto" diff --git a/api/tests/test_health.py b/api/tests/test_health.py new file mode 100644 index 0000000..336384a --- /dev/null +++ b/api/tests/test_health.py @@ -0,0 +1,12 @@ +import pytest +from httpx import ASGITransport, AsyncClient + +from app.main import app + + +@pytest.mark.asyncio +async def test_health(): + async with AsyncClient(transport=ASGITransport(app=app), base_url="http://test") as c: + r = await c.get("/health") + assert r.status_code == 200 + assert r.json() == {"status": "ok"} diff --git a/data/README.md b/data/README.md new file mode 100644 index 0000000..8d57f0e --- /dev/null +++ b/data/README.md @@ -0,0 +1,16 @@ +# Test data + +No patient data. Use public sources only: + +- ClinVar VCF (GRCh38): https://ftp.ncbi.nlm.nih.gov/pub/clinvar/vcf_GRCh38/ +- gnomAD exomes subset for allele frequencies +- A small HG002 (GIAB) chr22 slice for a realistic germline sample + +```bash +# Example: 2,000 ClinVar variants on chr22 as a smoke-test VCF +wget -O clinvar.vcf.gz https://ftp.ncbi.nlm.nih.gov/pub/clinvar/vcf_GRCh38/clinvar.vcf.gz +tabix -p vcf clinvar.vcf.gz +bcftools view -r 22 clinvar.vcf.gz | bcftools view -H | head -2000 > body.vcf +(bcftools view -h clinvar.vcf.gz; cat body.vcf) | bgzip > example.vcf.gz +tabix -p vcf example.vcf.gz +``` diff --git a/docker-compose.yml b/docker-compose.yml new file mode 100644 index 0000000..159ccc2 --- /dev/null +++ b/docker-compose.yml @@ -0,0 +1,45 @@ +services: + db: + image: postgres:16-alpine + environment: + POSTGRES_USER: rarelens + POSTGRES_PASSWORD: rarelens + POSTGRES_DB: rarelens + ports: ["5432:5432"] + volumes: [pgdata:/var/lib/postgresql/data] + healthcheck: + test: ["CMD-SHELL", "pg_isready -U rarelens"] + interval: 5s + retries: 10 + + api: + build: ./api + environment: + DATABASE_URL: postgresql+asyncpg://rarelens:rarelens@db:5432/rarelens + MLFLOW_TRACKING_URI: http://mlflow:5000 + ports: ["8000:8000"] + depends_on: + db: { condition: service_healthy } + volumes: ["./api:/app"] + command: uvicorn app.main:app --host 0.0.0.0 --port 8000 --reload + + web: + build: + context: ./web + target: build + environment: + PUBLIC_API_URL: http://localhost:8000 + ports: ["5173:5173"] + depends_on: [api] + volumes: ["./web:/app", "/app/node_modules"] + command: npm run dev -- --host + + mlflow: + image: ghcr.io/mlflow/mlflow:v2.16.0 + command: mlflow server --host 0.0.0.0 --backend-store-uri sqlite:///mlflow.db --default-artifact-root /mlruns + ports: ["5000:5000"] + volumes: [mlruns:/mlruns] + +volumes: + pgdata: + mlruns: diff --git a/docs/architecture.md b/docs/architecture.md new file mode 100644 index 0000000..ad015c0 --- /dev/null +++ b/docs/architecture.md @@ -0,0 +1,51 @@ +# Architecture + +```mermaid +flowchart LR + U[Scientist] -->|browser| W[SvelteKit web] + W -->|REST| A[FastAPI] + A --> P[(PostgreSQL / Cloud SQL)] + A -->|publish vcf-uploaded| Q[Pub/Sub] + Q --> E[Argo Events sensor] + E --> AW[Argo Workflow] + AW --> NF[Nextflow: bcftools norm, VEP, load_db] + NF -->|reads VCF| G[(GCS bucket)] + NF -->|writes variants| P + A -->|models:/rarelens-pathogenicity| M[MLflow registry] + T[ml/train.py on GKE, optional GPU] --> M + GH[GitHub Actions] -->|images via WIF| AR[Artifact Registry] + GH -->|bumps overlay tags| R[(git: infra/k8s/overlays/gcp)] + R --> CD[ArgoCD] --> K[GKE Autopilot] +``` + +## Why these choices + +**One monorepo.** The four components share a schema (`variants` table, feature columns) and the +point of the exercise is to see them evolve together. Separate repos would hide the coupling. + +**Nextflow for the science, Argo Workflows for the trigger.** Nextflow is the lingua franca for +bioinformatics pipelines and has a native Kubernetes executor. Argo is what the platform team +already runs. So Argo owns *when* a pipeline runs; Nextflow owns *what* it does. The API never +talks to Kubernetes directly; it publishes an event and gets on with its life. + +**FastAPI + Pydantic v2 + SQLAlchemy 2.0 async.** Typed at both boundaries: request/response models +and ORM models are separate on purpose so the database can change without breaking the frontend +contract. Alembic owns the schema; the loader script writes raw SQL against that schema, not the ORM, +because the pipeline container should not import the API. + +**SvelteKit.** Small runtime, no virtual DOM, and Svelte 5 runes make server-driven state simple. +The UI has exactly two pages; the goal is a table a scientist actually wants to filter, not a dashboard. + +**GKE Autopilot + Cloud SQL, not self-managed.** The lab is about the platform patterns (Workload +Identity, GitOps, Kustomize overlays, GPU node selection), not about running etcd. + +**GitOps.** CI builds and tests; it never runs `kubectl apply`. It edits image tags in the `gcp` overlay +and ArgoCD reconciles. Rollback is `git revert`. + +**MLflow registry as the model contract.** The API loads `models:/rarelens-pathogenicity/Production`. +Training writes there; serving reads there. Feature engineering lives in one module that both sides import. + +## What is deliberately missing + +Authentication, PHI handling, audit logs, clinical validation. This is a learning platform on public +data. Adding Identity-Aware Proxy in front of the ingress is the first step if that ever changes. diff --git a/infra/argo-workflows/annotate.yaml b/infra/argo-workflows/annotate.yaml new file mode 100644 index 0000000..cf7840d --- /dev/null +++ b/infra/argo-workflows/annotate.yaml @@ -0,0 +1,37 @@ +# Triggered by an Argo Events sensor listening on the Pub/Sub topic "vcf-uploaded". +apiVersion: argoproj.io/v1alpha1 +kind: WorkflowTemplate +metadata: { name: annotate-vcf, namespace: rarelens } +spec: + entrypoint: nextflow + arguments: + parameters: + - { name: job_id } + - { name: vcf_uri } + templates: + - name: nextflow + inputs: + parameters: [{ name: job_id }, { name: vcf_uri }] + serviceAccountName: rarelens-pipeline + container: + image: europe-west2-docker.pkg.dev/PROJECT/rarelens/pipeline:latest + command: [nextflow] + args: + - run + - /pipeline/main.nf + - -profile + - gcp + - --vcf + - "{{inputs.parameters.vcf_uri}}" + - --job_id + - "{{inputs.parameters.job_id}}" + - --db_url + - "$(DATABASE_URL)" + envFrom: [{ secretRef: { name: api-secrets } }] + resources: { requests: { cpu: "2", memory: 4Gi } } + - name: score + # Optional GPU step for the deep-learning baseline; Autopilot schedules on an L4 node. + nodeSelector: { cloud.google.com/gke-accelerator: nvidia-l4 } + container: + image: europe-west2-docker.pkg.dev/PROJECT/rarelens/ml:latest + resources: { limits: { nvidia.com/gpu: 1 } } diff --git a/infra/argocd/app.yaml b/infra/argocd/app.yaml new file mode 100644 index 0000000..2942462 --- /dev/null +++ b/infra/argocd/app.yaml @@ -0,0 +1,13 @@ +apiVersion: argoproj.io/v1alpha1 +kind: Application +metadata: { name: rarelens, namespace: argocd } +spec: + project: default + source: + repoURL: https://github.com/lynchaos/rarelens + targetRevision: main + path: infra/k8s/overlays/gcp + destination: { server: https://kubernetes.default.svc, namespace: rarelens } + syncPolicy: + automated: { prune: true, selfHeal: true } + syncOptions: [CreateNamespace=true] diff --git a/infra/k8s/base/api.yaml b/infra/k8s/base/api.yaml new file mode 100644 index 0000000..b7d4671 --- /dev/null +++ b/infra/k8s/base/api.yaml @@ -0,0 +1,26 @@ +apiVersion: apps/v1 +kind: Deployment +metadata: { name: api } +spec: + replicas: 2 + selector: { matchLabels: { app: api } } + template: + metadata: { labels: { app: api } } + spec: + serviceAccountName: rarelens-api + containers: + - name: api + image: rarelens/api + ports: [{ containerPort: 8000 }] + envFrom: [{ secretRef: { name: api-secrets } }] + readinessProbe: { httpGet: { path: /health, port: 8000 }, periodSeconds: 5 } + resources: { requests: { cpu: 250m, memory: 512Mi }, limits: { cpu: "1", memory: 1Gi } } +--- +apiVersion: v1 +kind: Service +metadata: { name: api } +spec: { selector: { app: api }, ports: [{ port: 80, targetPort: 8000 }] } +--- +apiVersion: v1 +kind: ServiceAccount +metadata: { name: rarelens-api } diff --git a/infra/k8s/base/ingress.yaml b/infra/k8s/base/ingress.yaml new file mode 100644 index 0000000..834aa93 --- /dev/null +++ b/infra/k8s/base/ingress.yaml @@ -0,0 +1,9 @@ +apiVersion: networking.k8s.io/v1 +kind: Ingress +metadata: { name: rarelens } +spec: + rules: + - http: + paths: + - { path: /api, pathType: Prefix, backend: { service: { name: api, port: { number: 80 } } } } + - { path: /, pathType: Prefix, backend: { service: { name: web, port: { number: 80 } } } } diff --git a/infra/k8s/base/kustomization.yaml b/infra/k8s/base/kustomization.yaml new file mode 100644 index 0000000..01f4a46 --- /dev/null +++ b/infra/k8s/base/kustomization.yaml @@ -0,0 +1,4 @@ +apiVersion: kustomize.config.k8s.io/v1beta1 +kind: Kustomization +namespace: rarelens +resources: [namespace.yaml, api.yaml, web.yaml, ingress.yaml] diff --git a/infra/k8s/base/namespace.yaml b/infra/k8s/base/namespace.yaml new file mode 100644 index 0000000..043b6a1 --- /dev/null +++ b/infra/k8s/base/namespace.yaml @@ -0,0 +1,3 @@ +apiVersion: v1 +kind: Namespace +metadata: { name: rarelens } diff --git a/infra/k8s/base/web.yaml b/infra/k8s/base/web.yaml new file mode 100644 index 0000000..b7ac555 --- /dev/null +++ b/infra/k8s/base/web.yaml @@ -0,0 +1,20 @@ +apiVersion: apps/v1 +kind: Deployment +metadata: { name: web } +spec: + replicas: 2 + selector: { matchLabels: { app: web } } + template: + metadata: { labels: { app: web } } + spec: + containers: + - name: web + image: rarelens/web + ports: [{ containerPort: 3000 }] + env: [{ name: PUBLIC_API_URL, value: /api }] + resources: { requests: { cpu: 100m, memory: 128Mi }, limits: { cpu: 500m, memory: 256Mi } } +--- +apiVersion: v1 +kind: Service +metadata: { name: web } +spec: { selector: { app: web }, ports: [{ port: 80, targetPort: 3000 }] } diff --git a/infra/k8s/overlays/gcp/kustomization.yaml b/infra/k8s/overlays/gcp/kustomization.yaml new file mode 100644 index 0000000..920593d --- /dev/null +++ b/infra/k8s/overlays/gcp/kustomization.yaml @@ -0,0 +1,21 @@ +apiVersion: kustomize.config.k8s.io/v1beta1 +kind: Kustomization +resources: [../../base] +images: + - { name: rarelens/api, newName: europe-west2-docker.pkg.dev/PROJECT/rarelens/api, newTag: latest } + - { name: rarelens/web, newName: europe-west2-docker.pkg.dev/PROJECT/rarelens/web, newTag: latest } +patches: + - target: { kind: ServiceAccount, name: rarelens-api } + patch: | + - op: add + path: /metadata/annotations + value: { iam.gke.io/gcp-service-account: rarelens-api@PROJECT.iam.gserviceaccount.com } + - target: { kind: Deployment, name: api } + patch: | + - op: add + path: /spec/template/spec/containers/- + value: + name: cloud-sql-proxy + image: gcr.io/cloud-sql-connectors/cloud-sql-proxy:2.13.0 + args: ["--structured-logs", "--port=5432", "PROJECT:europe-west2:rarelens-pg"] + securityContext: { runAsNonRoot: true } diff --git a/infra/k8s/overlays/local/kustomization.yaml b/infra/k8s/overlays/local/kustomization.yaml new file mode 100644 index 0000000..76e89f6 --- /dev/null +++ b/infra/k8s/overlays/local/kustomization.yaml @@ -0,0 +1,9 @@ +apiVersion: kustomize.config.k8s.io/v1beta1 +kind: Kustomization +resources: [../../base, postgres.yaml] +images: + - { name: rarelens/api, newName: rarelens-api, newTag: dev } + - { name: rarelens/web, newName: rarelens-web, newTag: dev } +secretGenerator: + - name: api-secrets + literals: [DATABASE_URL=postgresql+asyncpg://rarelens:rarelens@postgres:5432/rarelens] diff --git a/infra/k8s/overlays/local/postgres.yaml b/infra/k8s/overlays/local/postgres.yaml new file mode 100644 index 0000000..356fa68 --- /dev/null +++ b/infra/k8s/overlays/local/postgres.yaml @@ -0,0 +1,20 @@ +apiVersion: apps/v1 +kind: Deployment +metadata: { name: postgres } +spec: + selector: { matchLabels: { app: postgres } } + template: + metadata: { labels: { app: postgres } } + spec: + containers: + - name: postgres + image: postgres:16-alpine + env: + - { name: POSTGRES_USER, value: rarelens } + - { name: POSTGRES_PASSWORD, value: rarelens } + - { name: POSTGRES_DB, value: rarelens } +--- +apiVersion: v1 +kind: Service +metadata: { name: postgres } +spec: { selector: { app: postgres }, ports: [{ port: 5432 }] } diff --git a/infra/terraform/cloudsql.tf b/infra/terraform/cloudsql.tf new file mode 100644 index 0000000..e89a057 --- /dev/null +++ b/infra/terraform/cloudsql.tf @@ -0,0 +1,29 @@ +resource "google_sql_database_instance" "pg" { + name = "rarelens-pg" + database_version = "POSTGRES_16" + region = var.region + deletion_protection = false + + settings { + tier = "db-f1-micro" # lab budget; bump for real use + availability_type = "ZONAL" + backup_configuration { enabled = true } + ip_configuration { + ipv4_enabled = false + private_network = google_compute_network.vpc.id + } + } +} + +resource "google_sql_database" "rarelens" { + name = "rarelens" + instance = google_sql_database_instance.pg.name +} + +resource "google_sql_user" "api" { + name = "rarelens" + instance = google_sql_database_instance.pg.name + password = random_password.pg.result +} + +resource "random_password" "pg" { length = 32 } diff --git a/infra/terraform/gke.tf b/infra/terraform/gke.tf new file mode 100644 index 0000000..32951ac --- /dev/null +++ b/infra/terraform/gke.tf @@ -0,0 +1,9 @@ +resource "google_container_cluster" "rarelens" { + name = "rarelens" + location = var.region + enable_autopilot = true + deletion_protection = false + + workload_identity_config { workload_pool = "${var.project}.svc.id.goog" } + release_channel { channel = "REGULAR" } +} diff --git a/infra/terraform/iam.tf b/infra/terraform/iam.tf new file mode 100644 index 0000000..3fa4343 --- /dev/null +++ b/infra/terraform/iam.tf @@ -0,0 +1,50 @@ +# Workload Identity Federation: GitHub Actions pushes images without long-lived keys. +resource "google_iam_workload_identity_pool" "github" { + workload_identity_pool_id = "github" +} + +resource "google_iam_workload_identity_pool_provider" "github" { + workload_identity_pool_id = google_iam_workload_identity_pool.github.workload_identity_pool_id + workload_identity_pool_provider_id = "github" + attribute_mapping = { + "google.subject" = "assertion.sub" + "attribute.repository" = "assertion.repository" + } + attribute_condition = "assertion.repository == \"${var.github_repo}\"" + oidc { issuer_uri = "https://token.actions.githubusercontent.com" } +} + +resource "google_service_account" "ci" { account_id = "rarelens-ci" } + +resource "google_service_account_iam_member" "ci_wif" { + service_account_id = google_service_account.ci.name + role = "roles/iam.workloadIdentityUser" + member = "principalSet://iam.googleapis.com/${google_iam_workload_identity_pool.github.name}/attribute.repository/${var.github_repo}" +} + +resource "google_artifact_registry_repository_iam_member" "ci_push" { + repository = google_artifact_registry_repository.images.name + location = var.region + role = "roles/artifactregistry.writer" + member = "serviceAccount:${google_service_account.ci.email}" +} + +# Runtime identities (bound to k8s ServiceAccounts via GKE Workload Identity) +resource "google_service_account" "api" { account_id = "rarelens-api" } +resource "google_service_account" "pipeline" { account_id = "rarelens-pipeline" } + +resource "google_project_iam_member" "api_sql" { + project = var.project + role = "roles/cloudsql.client" + member = "serviceAccount:${google_service_account.api.email}" +} +resource "google_project_iam_member" "api_pubsub" { + project = var.project + role = "roles/pubsub.publisher" + member = "serviceAccount:${google_service_account.api.email}" +} +resource "google_storage_bucket_iam_member" "pipeline_data" { + bucket = google_storage_bucket.data.name + role = "roles/storage.objectAdmin" + member = "serviceAccount:${google_service_account.pipeline.email}" +} diff --git a/infra/terraform/network.tf b/infra/terraform/network.tf new file mode 100644 index 0000000..224f31b --- /dev/null +++ b/infra/terraform/network.tf @@ -0,0 +1,4 @@ +resource "google_compute_network" "vpc" { + name = "rarelens-vpc" + auto_create_subnetworks = true +} diff --git a/infra/terraform/outputs.tf b/infra/terraform/outputs.tf new file mode 100644 index 0000000..79d32ac --- /dev/null +++ b/infra/terraform/outputs.tf @@ -0,0 +1,5 @@ +output "cluster_name" { value = google_container_cluster.rarelens.name } +output "sql_connection" { value = google_sql_database_instance.pg.connection_name } +output "data_bucket" { value = google_storage_bucket.data.name } +output "wif_provider" { value = google_iam_workload_identity_pool_provider.github.name } +output "ci_sa" { value = google_service_account.ci.email } diff --git a/infra/terraform/storage.tf b/infra/terraform/storage.tf new file mode 100644 index 0000000..e226157 --- /dev/null +++ b/infra/terraform/storage.tf @@ -0,0 +1,20 @@ +resource "google_storage_bucket" "data" { + name = "${var.project}-rarelens-data" + location = var.region + uniform_bucket_level_access = true + lifecycle_rule { + condition { + age = 30 + matches_prefix = ["work/"] + } + action { type = "Delete" } + } +} + +resource "google_artifact_registry_repository" "images" { + repository_id = "rarelens" + location = var.region + format = "DOCKER" +} + +resource "google_pubsub_topic" "vcf_uploaded" { name = "vcf-uploaded" } diff --git a/infra/terraform/variables.tf b/infra/terraform/variables.tf new file mode 100644 index 0000000..490a316 --- /dev/null +++ b/infra/terraform/variables.tf @@ -0,0 +1,9 @@ +variable "project" { type = string } +variable "region" { + type = string + default = "europe-west2" # London: keeps public genomic test data and the Cambridge team in one jurisdiction +} +variable "github_repo" { + type = string + default = "lynchaos/rarelens" +} diff --git a/infra/terraform/versions.tf b/infra/terraform/versions.tf new file mode 100644 index 0000000..449370e --- /dev/null +++ b/infra/terraform/versions.tf @@ -0,0 +1,13 @@ +terraform { + required_version = ">= 1.8" + required_providers { + google = { source = "hashicorp/google", version = "~> 6.0" } + random = { source = "hashicorp/random", version = "~> 3.6" } + } + backend "gcs" { bucket = "REPLACE-tfstate", prefix = "rarelens" } +} + +provider "google" { + project = var.project + region = var.region +} diff --git a/ml/Dockerfile b/ml/Dockerfile new file mode 100644 index 0000000..a2323df --- /dev/null +++ b/ml/Dockerfile @@ -0,0 +1,7 @@ +FROM python:3.12-slim +WORKDIR /ml +RUN pip install --no-cache-dir uv +COPY pyproject.toml . +RUN uv pip install --system -e . +COPY rarelens_ml ./rarelens_ml +ENTRYPOINT ["python", "-m", "rarelens_ml.train"] diff --git a/ml/pyproject.toml b/ml/pyproject.toml new file mode 100644 index 0000000..af80f6f --- /dev/null +++ b/ml/pyproject.toml @@ -0,0 +1,8 @@ +[project] +name = "rarelens-ml" +version = "0.1.0" +requires-python = ">=3.12" +dependencies = ["lightgbm>=4.5", "mlflow>=2.16", "pandas", "scikit-learn", "sqlalchemy", "psycopg[binary]"] + +[project.optional-dependencies] +gpu = ["torch"] # for the optional deep-learning baseline on GPU diff --git a/ml/rarelens_ml/__init__.py b/ml/rarelens_ml/__init__.py new file mode 100644 index 0000000..e69de29 diff --git a/ml/rarelens_ml/features.py b/ml/rarelens_ml/features.py new file mode 100644 index 0000000..8a9c35e --- /dev/null +++ b/ml/rarelens_ml/features.py @@ -0,0 +1,16 @@ +"""Feature engineering shared by training and serving. Keep this identical to api/app/services/scoring.py.""" +import pandas as pd + +IMPACT_ORDER = {"MODIFIER": 0, "LOW": 1, "MODERATE": 2, "HIGH": 3} +CATEGORICAL = ["consequence"] +NUMERIC = ["impact_rank", "gnomad_af", "cadd_phred", "am_pathogenicity"] + + +def build(df: pd.DataFrame) -> pd.DataFrame: + out = pd.DataFrame() + out["impact_rank"] = df["impact"].map(IMPACT_ORDER).fillna(0) + out["gnomad_af"] = pd.to_numeric(df["gnomad_af"], errors="coerce").fillna(0.0) + out["cadd_phred"] = pd.to_numeric(df["cadd_phred"], errors="coerce") + out["am_pathogenicity"] = pd.to_numeric(df["am_pathogenicity"], errors="coerce") + out["consequence"] = df["consequence"].astype("category") + return out diff --git a/ml/rarelens_ml/train.py b/ml/rarelens_ml/train.py new file mode 100644 index 0000000..ed0d392 --- /dev/null +++ b/ml/rarelens_ml/train.py @@ -0,0 +1,55 @@ +"""Train a pathogenicity classifier on ClinVar labels (Pathogenic/Likely pathogenic vs Benign/Likely benign). + +Label leakage warning: CLIN_SIG must never be a feature. This is a learning exercise, not a clinical model. +Usage: python -m rarelens_ml.train --tsv results/clinvar.vep.tsv +""" +import argparse + +import lightgbm as lgb +import mlflow +import mlflow.lightgbm +import pandas as pd +from sklearn.metrics import average_precision_score, roc_auc_score +from sklearn.model_selection import train_test_split + +from rarelens_ml.features import build + +POS = {"Pathogenic", "Likely_pathogenic", "Pathogenic/Likely_pathogenic"} +NEG = {"Benign", "Likely_benign", "Benign/Likely_benign"} + + +def load(tsv: str) -> tuple[pd.DataFrame, pd.Series]: + df = pd.read_csv(tsv, sep="\t", comment="#", header=None, dtype=str) + with open(tsv) as fh: + df.columns = next(l for l in fh if l.startswith("#Uploaded")).lstrip("#").rstrip().split("\t") + df = df.rename(columns={"IMPACT": "impact", "Consequence": "consequence", "gnomADe_AF": "gnomad_af", + "CADD_PHRED": "cadd_phred"}) + y = df["CLIN_SIG"].map(lambda s: 1 if s in POS else 0 if s in NEG else None) + keep = y.notna() + return build(df[keep]), y[keep].astype(int) + + +def main() -> None: + p = argparse.ArgumentParser() + p.add_argument("--tsv", required=True) + p.add_argument("--register", action="store_true") + a = p.parse_args() + + X, y = load(a.tsv) + Xtr, Xte, ytr, yte = train_test_split(X, y, test_size=0.2, stratify=y, random_state=42) + + mlflow.set_experiment("rarelens-pathogenicity") + with mlflow.start_run(): + params = {"n_estimators": 400, "learning_rate": 0.05, "num_leaves": 31, "class_weight": "balanced"} + mlflow.log_params(params) + model = lgb.LGBMClassifier(**params).fit(Xtr, ytr) + proba = model.predict_proba(Xte)[:, 1] + mlflow.log_metrics({"auroc": roc_auc_score(yte, proba), "auprc": average_precision_score(yte, proba)}) + mlflow.lightgbm.log_model( + model, "model", + registered_model_name="rarelens-pathogenicity" if a.register else None, + ) + + +if __name__ == "__main__": + main() diff --git a/pipeline/Dockerfile b/pipeline/Dockerfile new file mode 100644 index 0000000..20f1b61 --- /dev/null +++ b/pipeline/Dockerfile @@ -0,0 +1,5 @@ +# Loader image: pandas + psycopg for LOAD_DB +FROM python:3.12-slim +RUN pip install --no-cache-dir pandas sqlalchemy "psycopg[binary]" +COPY bin/load_db.py /usr/local/bin/load_db.py +RUN chmod +x /usr/local/bin/load_db.py diff --git a/pipeline/bin/load_db.py b/pipeline/bin/load_db.py new file mode 100755 index 0000000..7aa62e4 --- /dev/null +++ b/pipeline/bin/load_db.py @@ -0,0 +1,61 @@ +#!/usr/bin/env python +"""Load a VEP --tab output into the rarelens Postgres schema and mark the job succeeded.""" +import argparse +import json +import sys + +import pandas as pd +from sqlalchemy import create_engine, text + + +def main() -> None: + p = argparse.ArgumentParser() + p.add_argument("--tsv", required=True) + p.add_argument("--job-id", required=True) + p.add_argument("--db-url", required=True) + a = p.parse_args() + + df = pd.read_csv(a.tsv, sep="\t", comment="#", header=None, dtype=str) + with open(a.tsv) as fh: + header = next(l for l in fh if l.startswith("#Uploaded_variation")).lstrip("#").rstrip().split("\t") + df.columns = header + + chrom_pos = df["Location"].str.split(":", expand=True) + rows = [] + for i, r in df.iterrows(): + ref, _, alt = r["Uploaded_variation"].partition("/") if "/" in r["Uploaded_variation"] else ("", "", r["Allele"]) + rows.append({ + "job_id": a.job_id, + "chrom": chrom_pos.iloc[i, 0], + "pos": int(chrom_pos.iloc[i, 1].split("-")[0]), + "ref": ref or "-", + "alt": r["Allele"], + "gene": r.get("SYMBOL") if r.get("SYMBOL") != "-" else None, + "consequence": r["Consequence"], + "impact": r["IMPACT"], + "hgvsc": None if r.get("HGVSc") == "-" else r.get("HGVSc"), + "hgvsp": None if r.get("HGVSp") == "-" else r.get("HGVSp"), + "gnomad_af": None if r.get("gnomADe_AF", "-") == "-" else float(r["gnomADe_AF"]), + "clinvar_sig": None if r.get("CLIN_SIG", "-") == "-" else r["CLIN_SIG"], + "annotations": json.dumps({k: v for k, v in r.items() if v != "-"}), + }) + + if a.db_url == "none": + print(f"{len(rows)} variants parsed (dry run, no DB)") + return + + engine = create_engine(a.db_url.replace("+asyncpg", "+psycopg")) + with engine.begin() as conn: + conn.execute(text(""" + INSERT INTO variants (job_id, chrom, pos, ref, alt, gene, consequence, impact, + hgvsc, hgvsp, gnomad_af, clinvar_sig, annotations) + VALUES (:job_id, :chrom, :pos, :ref, :alt, :gene, :consequence, :impact, + :hgvsc, :hgvsp, :gnomad_af, :clinvar_sig, CAST(:annotations AS jsonb)) + """), rows) + conn.execute(text("UPDATE jobs SET status='succeeded', finished_at=now() WHERE id=:id"), + {"id": a.job_id}) + print(f"loaded {len(rows)} variants for job {a.job_id}", file=sys.stderr) + + +if __name__ == "__main__": + main() diff --git a/pipeline/main.nf b/pipeline/main.nf new file mode 100644 index 0000000..1e6c874 --- /dev/null +++ b/pipeline/main.nf @@ -0,0 +1,15 @@ +#!/usr/bin/env nextflow +nextflow.enable.dsl = 2 + +include { NORMALISE } from './modules/normalise' +include { VEP } from './modules/vep' +include { LOAD_DB } from './modules/load_db' + +workflow { + if (!params.vcf) error "Provide --vcf" + vcf_ch = Channel.fromPath(params.vcf, checkIfExists: true) + + NORMALISE(vcf_ch) + VEP(NORMALISE.out.vcf) + LOAD_DB(VEP.out.tsv, params.job_id ?: 'local', params.db_url ?: 'none') +} diff --git a/pipeline/modules/load_db.nf b/pipeline/modules/load_db.nf new file mode 100644 index 0000000..fe3c778 --- /dev/null +++ b/pipeline/modules/load_db.nf @@ -0,0 +1,13 @@ +process LOAD_DB { + tag "$job_id" + input: + path tsv + val job_id + val db_url + output: stdout + + script: + """ + load_db.py --tsv $tsv --job-id $job_id --db-url '$db_url' + """ +} diff --git a/pipeline/modules/normalise.nf b/pipeline/modules/normalise.nf new file mode 100644 index 0000000..a566c0c --- /dev/null +++ b/pipeline/modules/normalise.nf @@ -0,0 +1,11 @@ +process NORMALISE { + tag "$vcf.simpleName" + input: path vcf + output: path "${vcf.simpleName}.norm.vcf.gz", emit: vcf + + script: + """ + bcftools norm -m -both -Oz -o ${vcf.simpleName}.norm.vcf.gz $vcf + bcftools index -t ${vcf.simpleName}.norm.vcf.gz + """ +} diff --git a/pipeline/modules/vep.nf b/pipeline/modules/vep.nf new file mode 100644 index 0000000..e12be3c --- /dev/null +++ b/pipeline/modules/vep.nf @@ -0,0 +1,16 @@ +process VEP { + tag "$vcf.simpleName" + publishDir params.outdir, mode: 'copy' + input: path vcf + output: + path "${vcf.simpleName}.vep.tsv", emit: tsv + path "${vcf.simpleName}.vep_summary.html" + + script: + """ + vep -i $vcf -o ${vcf.simpleName}.vep.tsv --tab \\ + --assembly ${params.assembly} --cache --dir_cache ${params.vep_cache} --offline \\ + --everything --pick --af_gnomade --plugin CADD --plugin AlphaMissense \\ + --stats_file ${vcf.simpleName}.vep_summary.html --fork ${task.cpus} + """ +} diff --git a/pipeline/nextflow.config b/pipeline/nextflow.config new file mode 100644 index 0000000..df697ab --- /dev/null +++ b/pipeline/nextflow.config @@ -0,0 +1,24 @@ +params { + vcf = null + job_id = null + db_url = null + outdir = "results" + assembly = "GRCh38" + vep_cache = "${projectDir}/cache/vep" // download once with `vep_install`; or use --offline false + vep_plugins = "CADD,AlphaMissense" +} + +profiles { + docker { docker.enabled = true } + gcp { + process.executor = 'k8s' // runs inside GKE via Argo; Nextflow k8s executor + workDir = "gs://${params.bucket}/work" + google.project = params.project + } +} + +process { + withName: VEP { container = 'ensemblorg/ensembl-vep:release_113.0'; cpus = 4; memory = '8 GB' } + withName: NORMALISE { container = 'quay.io/biocontainers/bcftools:1.20--h8b25389_0' } + withName: LOAD_DB { container = 'ghcr.io/lynchaos/rarelens-loader:latest' } +} diff --git a/web/.env b/web/.env new file mode 100644 index 0000000..7f13e1b --- /dev/null +++ b/web/.env @@ -0,0 +1 @@ +PUBLIC_API_URL=http://localhost:8000 \ No newline at end of file diff --git a/web/Dockerfile b/web/Dockerfile new file mode 100644 index 0000000..e090e39 --- /dev/null +++ b/web/Dockerfile @@ -0,0 +1,14 @@ +FROM node:22-alpine AS build +WORKDIR /app +COPY package*.json ./ +RUN npm ci +COPY . . +RUN npm run build + +FROM node:22-alpine +WORKDIR /app +COPY --from=build /app/build ./build +COPY --from=build /app/package*.json ./ +RUN npm ci --omit=dev +EXPOSE 3000 +CMD ["node", "build"] diff --git a/web/package-lock.json b/web/package-lock.json new file mode 100644 index 0000000..e7951ee --- /dev/null +++ b/web/package-lock.json @@ -0,0 +1,2217 @@ +{ + "name": "rarelens-web", + "version": "0.1.0", + "lockfileVersion": 3, + "requires": true, + "packages": { + "": { + "name": "rarelens-web", + "version": "0.1.0", + "devDependencies": { + "@sveltejs/adapter-node": "^5.2.0", + "@sveltejs/kit": "^2.5.0", + "@sveltejs/vite-plugin-svelte": "^4.0.0", + "svelte": "^5.0.0", + "svelte-check": "^4.0.0", + "typescript": "^5.5.0", + "vite": "^5.4.0", + "vitest": "^2.0.0" + } + }, + "node_modules/@esbuild/aix-ppc64": { + "version": "0.21.5", + "resolved": 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"svelte": "^5.0.0", + "svelte-check": "^4.0.0", + "typescript": "^5.5.0", + "vite": "^5.4.0", + "vitest": "^2.0.0" + } +} diff --git a/web/src/app.css b/web/src/app.css new file mode 100644 index 0000000..d0b82e5 --- /dev/null +++ b/web/src/app.css @@ -0,0 +1,35 @@ +/* Palette: pale slate paper, ink navy, and one plum accent reserved for pathogenicity. */ +:root { + --paper: #f3f5f7; + --ink: #16243a; + --ink-soft: #52627a; + --line: #cfd6df; + --plum: #7a1f5c; + --plum-soft: #f0dbe8; + --amber: #b86a00; + --mono: 'JetBrains Mono', ui-monospace, monospace; + --sans: 'Source Sans 3', system-ui, sans-serif; +} +html { background: var(--paper); color: var(--ink); font-family: var(--sans); font-size: 17px; } +body { margin: 0; } +main { max-width: 1100px; margin: 0 auto; padding: 2.5rem 1.5rem; } +h1 { font-weight: 600; font-size: 2rem; letter-spacing: -0.01em; margin: 0 0 0.5rem; } +h2 { font-weight: 600; font-size: 1.25rem; margin: 2rem 0 0.75rem; } +p.lede { color: var(--ink-soft); max-width: 60ch; margin: 0 0 2rem; } +a { color: var(--plum); text-underline-offset: 3px; } +a:focus-visible, button:focus-visible, input:focus-visible, select:focus-visible { outline: 3px solid var(--plum); outline-offset: 2px; } +button { font: inherit; padding: 0.5rem 1rem; border: 1.5px solid var(--ink); background: var(--ink); color: white; border-radius: 4px; cursor: pointer; } +button.quiet { background: transparent; color: var(--ink); } +input, select { font: inherit; padding: 0.45rem 0.6rem; border: 1.5px solid var(--line); border-radius: 4px; background: white; } +table { width: 100%; border-collapse: collapse; background: white; border: 1px solid var(--line); } +th, td { text-align: left; padding: 0.55rem 0.75rem; border-bottom: 1px solid var(--line); vertical-align: top; } +th { font-weight: 600; color: var(--ink-soft); } +td.coord, td.hgvs { font-family: var(--mono); font-size: 0.85rem; } /* aligned digits matter here */ +.score { display: inline-block; min-width: 3.2rem; text-align: right; padding: 0.1rem 0.4rem; border-radius: 3px; font-variant-numeric: tabular-nums; } +.score.high { background: var(--plum); color: white; } +.score.mid { background: var(--plum-soft); color: var(--plum); } +.empty { padding: 2rem; border: 1.5px dashed var(--line); color: var(--ink-soft); } +.status { font-weight: 600; } +.status.failed { color: #9a1b1b; } +.status.running, .status.queued { color: var(--amber); } +@media (prefers-reduced-motion: no-preference) { button { transition: background 120ms; } } diff --git a/web/src/app.html b/web/src/app.html new file mode 100644 index 0000000..42fbe6b --- /dev/null +++ b/web/src/app.html @@ -0,0 +1,13 @@ + + + + + + + + %sveltekit.head% + + +
%sveltekit.body%
+ + diff --git a/web/src/lib/api.ts b/web/src/lib/api.ts new file mode 100644 index 0000000..4ffc62f --- /dev/null +++ b/web/src/lib/api.ts @@ -0,0 +1,25 @@ +import { PUBLIC_API_URL } from '$env/static/public'; + +export type Sample = { id: string; name: string; vcf_uri: string; assembly: string; created_at: string }; +export type Job = { id: string; sample_id: string; status: 'queued' | 'running' | 'succeeded' | 'failed'; created_at: string; finished_at: string | null }; +export type Variant = { + id: number; chrom: string; pos: number; ref: string; alt: string; gene: string | null; + consequence: string | null; impact: string | null; hgvsc: string | null; hgvsp: string | null; + gnomad_af: number | null; clinvar_sig: string | null; prediction: { score: number; model_version: string } | null; +}; +export type VariantPage = { items: Variant[]; total: number; limit: number; offset: number }; + +async function req(path: string, init?: RequestInit): Promise { + const r = await fetch(`${PUBLIC_API_URL}${path}`, { headers: { 'content-type': 'application/json' }, ...init }); + if (!r.ok) throw new Error(`${r.status} ${r.statusText} on ${path}`); + return r.json() as Promise; +} + +export const api = { + samples: () => req('/samples'), + createSample: (body: Pick) => req('/samples', { method: 'POST', body: JSON.stringify(body) }), + jobsForSample: (sampleId: string) => req(`/samples/${sampleId}/jobs`), + annotate: (sampleId: string) => req(`/samples/${sampleId}/annotate`, { method: 'POST' }), + job: (id: string) => req(`/jobs/${id}`), + variants: (q: Record) => req(`/variants?${new URLSearchParams(q as Record)}`) +}; diff --git a/web/src/routes/+layout.svelte b/web/src/routes/+layout.svelte new file mode 100644 index 0000000..61e2a60 --- /dev/null +++ b/web/src/routes/+layout.svelte @@ -0,0 +1,6 @@ + + +
{@render children()}
diff --git a/web/src/routes/+page.svelte b/web/src/routes/+page.svelte new file mode 100644 index 0000000..026a4ba --- /dev/null +++ b/web/src/routes/+page.svelte @@ -0,0 +1,48 @@ + + +

rarelens

+

Annotate a VCF with Ensembl VEP, score each variant, and browse what came back. Public test data only.

+ +

Add a sample

+
+ + + +
+{#if error}

Could not add the sample: {error}

{/if} + +

Samples

+{#if samples.length === 0} +
No samples yet. Add one above to run the annotation pipeline.
+{:else} + + + + {#each samples as s (s.id)} + + + + + + + {/each} + +
NameVCFAssemblyAdded
{s.name}{s.vcf_uri}{s.assembly}{new Date(s.created_at).toLocaleDateString('en-GB')}
+{/if} diff --git a/web/src/routes/samples/[id]/+page.svelte b/web/src/routes/samples/[id]/+page.svelte new file mode 100644 index 0000000..c8ef3aa --- /dev/null +++ b/web/src/routes/samples/[id]/+page.svelte @@ -0,0 +1,82 @@ + + +All samples +

Sample {data.sampleId.slice(0, 8)}

+ +{#if !job} + +{:else} +

Job {job.id.slice(0, 8)}: {job.status}

+{/if} + +{#if job?.status === 'succeeded'} +

Variants

+
+ + + + +
+ + {#if page && page.items.length === 0} +
No variants match these filters. Raise the allele frequency cap or clear the gene filter.
+ {:else if page} +

{page.total} variants, showing {page.items.length}

+ + + + {#each page.items as v (v.id)} + + + + + + + + + + {/each} + +
PositionGeneConsequenceHGVSgnomAD AFClinVarScore
{v.chrom}:{v.pos} {v.ref}>{v.alt}{v.gene ?? ''}{v.consequence ?? ''}
{v.impact ?? ''}		{v.hgvsp ?? v.hgvsc ?? ''}{v.gnomad_af?.toExponential(2) ?? 'absent'}{v.clinvar_sig ?? ''}{#if v.prediction}{v.prediction.score.toFixed(2)}{:else}unscored{/if}
+ {/if} +{/if} diff --git a/web/src/routes/samples/[id]/+page.ts b/web/src/routes/samples/[id]/+page.ts new file mode 100644 index 0000000..6effbd8 --- /dev/null +++ b/web/src/routes/samples/[id]/+page.ts @@ -0,0 +1,2 @@ +import type { PageLoad } from './$types'; +export const load: PageLoad = ({ params }) => ({ sampleId: params.id }); diff --git a/web/svelte.config.js b/web/svelte.config.js new file mode 100644 index 0000000..34057a6 --- /dev/null +++ b/web/svelte.config.js @@ -0,0 +1,7 @@ +import adapter from '@sveltejs/adapter-node'; +import { vitePreprocess } from '@sveltejs/vite-plugin-svelte'; + +export default { + preprocess: vitePreprocess(), + kit: { adapter: adapter() } +}; diff --git a/web/tsconfig.json b/web/tsconfig.json new file mode 100644 index 0000000..232f336 --- /dev/null +++ b/web/tsconfig.json @@ -0,0 +1,4 @@ +{ + "extends": "./.svelte-kit/tsconfig.json", + "compilerOptions": { "strict": true, "moduleResolution": "bundler" } +} diff --git a/web/vite.config.ts b/web/vite.config.ts new file mode 100644 index 0000000..8aa96a3 --- /dev/null +++ b/web/vite.config.ts @@ -0,0 +1,3 @@ +import { sveltekit } from '@sveltejs/kit/vite'; +import { defineConfig } from 'vite'; +export default defineConfig({ plugins: [sveltekit()], server: { port: 5173 } });