hvantk-resource-clinvar

name: hvantk:resource-clinvar description: Onboard, build, or update the ClinVar resource for hvantk status: provisional backend: hail domain: variants

ClinVar resource skill

1. Status & scope

This skill covers BUILD and UPDATE of the ClinVar Hail Table. It does NOT cover download (see hvantk/skills/clinvar/cli.py) or downstream analysis.

The builder is build_clinvar in hvantk/skills/clinvar/builder.py. It has the platform builder signature build_clinvar(parsed_input, ctx, *, reference_genome="GRCh38") -> AnnotationTable. There is no input_path / output_path / overwrite / export_tsv signature; the platform's run_builder_for_spec calls artifact.save() to materialize the table.

2. Source identity

Provider metadata (URL, version cadence, license, citation) lives in the ClinVar entry inside hvantk/resources/registry/genomics/datasets.json (find by accession: "ClinVar_latest"), surfaced via hvantk catalog show ClinVar_latest. Read that file; do not restate.

Stable note (not in catalog): ClinVar releases monthly. New INFO fields are uncommon but do occur (e.g., the addition of ONCOGENICITY in the oncogenicity supplement).

3. Backend choice + reasoning

Hail Table keyed by (locus, alleles). Reasoning: ClinVar is variant-keyed and joins with other variant tables (gnomAD, dbNSFP) downstream. A single Hail Table is the natural fit; nothing about ClinVar requires anndata or pandas.

4. Raw format & gotchas

• File format: bgzipped VCF (.vcf.bgz with .tbi index).
• Reference genome: GRCh38 by default. The contig_recoding() helper from hvantk/core/utils/genome.py maps numeric contigs to chr* names.
• Import: use hl.import_vcf(path, force=True, reference_genome=..., contig_recoding=..., skip_invalid_loci=True). The force=True flag is required because ClinVar VCFs contain non-standard headers.
• Keying: after .rows(), repartition (typical: 100) and key by (locus, alleles).
• INFO fields commonly used: CLNSIG, CLNREVSTAT, CLNDN, CLNDISDB, RS, MC, GENEINFO. The full list comes from the VCF header — read it, do not assume.
• Encoding gotchas:
  • Spaces in INFO values are encoded as _ (e.g., Likely_pathogenic).
  • Multi-value INFO fields use , or | depending on the field.
  • CLNDISDB uses , between databases and | between IDs within a database.

5. Output contract

AnnotationTable wrapping a Hail Table keyed by (locus, alleles), with provenance schema_id="clinvar-variants-v1". The platform writes it to the build --output path. Schema is defined by hvantk/skills/clinvar/tests/snapshots/schema.json (canonical). Human summary: row contains rsid, qual, filters, and an info struct with the ClinVar-specific INFO fields parsed by hl.import_vcf.

6. hvantk integration points

• Builder: build_clinvar in hvantk/skills/clinvar/builder.py
• Streamer: ClinVarVariantTableStreamer in hvantk/skills/clinvar/streamers.py (subclass of VariantTableStreamer in hvantk/core/streamers/)
• Downloader CLI: clinvar_downloader in hvantk/skills/clinvar/cli.py (registered as hvantk clinvar-download; lifecycle download via download_dataset in the same module)
• Dataset class: ClinVarDataset in hvantk/skills/clinvar/shared/datasets.py
• Build CLI: hvantk reprocess clinvar:variants --raw-dir <dir> --output <path>.ht (pass builder kwargs via --plugin-arg KEY=VALUE, e.g. --plugin-arg reference_genome=GRCh38). The plugin loader (hvantk/core/plugin/loader.py) resolves the dataset from plugin.yaml via get_registry().get_dataset("clinvar:variants"); the build runs through run_builder_for_spec (hvantk/core/plugin/run_builder.py).
• Plugin manifest: hvantk/skills/clinvar/plugin.yaml (drives loader registration; compound dataset key clinvar:variants)
• Test: hvantk/skills/clinvar/tests/test_builder.py

Read the existing files at these paths as ground truth for shape. This skill does not restate code.

7. Workflow steps

When invoked to build or update:

1. Verify Hail is available (defer to the SessionStart hook).
2. Confirm input is a ClinVar VCF: read the #CHROM header line of the input file.
3. Build the table inline in build_clinvar (no shared base helper):
   • hl.import_vcf(str(parsed_input), force=True, reference_genome=reference_genome, contig_recoding=contig_recoding(), skip_invalid_loci=True).rows()
   • .repartition(100).key_by("locus", "alleles")
   • Wrap the result with AnnotationTable.from_hail(ht, provenance=ctx.provenance(schema_id="clinvar-variants-v1")). The platform calls artifact.save() to write to disk.
4. Apply the parsing rules from § 4 (force, contig_recoding, skip_invalid_loci).
5. Run validation: pytest hvantk/skills/clinvar/tests -m hail.
6. Report: schema diff, sample-row diff, test pass/fail.

8. Update playbook

When ClinVar releases a new monthly version:

1. Fetch the new release: hvantk clinvar-download --output-dir /tmp/clinvar.
2. Regenerate the fixture: extract a small representative slice (mix of CLNSIG values, multi-allelic site, multi-CLNDN row). The current pilot fixture is a single-chromosome slice (hvantk/skills/clinvar/tests/testdata/raw/clinvar/clinvar_20220403_chr20.vcf.bgz) — this is adequate because ClinVar parsing is INFO-field driven, not chromosome-dependent. Replace the file (re-bgzip if needed). A .tbi index is optional; hl.import_vcf(force=True) reads .bgz directly.
3. Run snapshot regeneration: pytest hvantk/skills/clinvar/tests -m hail --regenerate-snapshots.
4. Inspect the snapshot diff:
   • Expected diff (new INFO field, additional CLNSIG value): commit the regenerated snapshots with explanation.
   • Unexpected diff (schema regression, missing field): STOP. Investigate before committing.
5. If a parsing gotcha was introduced (e.g., new encoding), add it to § 4.
6. Open PR; reviewer checks the snapshot diff narrative.

9. Validation contract

• fixture: hvantk/skills/clinvar/tests/testdata/raw/clinvar/clinvar_20220403_chr20.vcf.bgz
• schema_snapshot: hvantk/skills/clinvar/tests/snapshots/schema.json
• row_snapshot: hvantk/skills/clinvar/tests/snapshots/sample_rows.json
• drift_fingerprint: hvantk/skills/clinvar/tests/drift_fingerprint.json
• test_command: pytest hvantk/skills/clinvar/tests -m hail