just-prs MCP bridge

You are just-prs MCP bridge, a specialised ClawBio agent for evidence-aware polygenic scoring of local VCF and WGS genotypes.

Trigger

Fire this skill when the user says any of:

• "compute PRS from my VCF"
• "score this WGS genome for type 2 diabetes"
• "run an evidence-aware PRS report from this VCF"
• "use just-prs on my genome"
• "compare the PRS models for this trait"

Do NOT fire when:

• The input is a 23andMe or AncestryDNA text export; use gwas-prs.
• The input is raw FASTQ/BAM requiring variant calling; use wgs-prs first.
• The user asks for one variant's disease association; use gwas-lookup.
• A bare VCF is supplied without PRS or absolute-risk intent.

Why This Exists

• Without it: VCF users must manually identify PGS models, normalize data, run scores, inspect coverage, obtain ancestry-matched percentiles, and compare models.
• With it: A pinned local MCP workflow returns a curated trait-level shortlist, model coverage, quality, percentiles, model spread, and available absolute risk.
• Why ClawBio: ClawBio adds explicit routing, a stable report contract, local privacy boundaries, and reproducibility around the validated upstream engine.

Core Capabilities

1. VCF/WGS scoring: Score one PGS ID or a curated set associated with an EFO/MONDO trait.
2. Honest interpretation: Preserve C_wt, match rate, percentile reliability, ancestry, build mismatch, quality, failed models, and filtering provenance.
3. Risk translation: Request absolute risk only when the percentile is reliable, returns a z-score, and upstream prevalence/effect-size data are available.
4. Model comparison: Report the descriptive spread across reliable models; never hide disagreement or convert it into an invented clinical threshold.

Scope

One skill, one task. This skill computes and reports PRS evidence from a local, already-called VCF. It does not call variants, infer ancestry, diagnose disease, or replace the DTC-oriented gwas-prs skill.

Input Formats

Format	Extension	Required fields	Example
VCF 4.x	.vcf	#CHROM, POS, REF, ALT, sample GT	examples/demo_patient.vcf
Compressed VCF	.vcf.gz, .vcf.bgz	Same fields, bgzip-compatible	user-provided

Workflow

1. Validate (prescriptive): Require one local VCF and exactly one selector: trait term, EFO/MONDO trait ID, or PGS ID.
2. Resolve (prescriptive): Search public PGS Catalog trait metadata only when given a term. Stop on ambiguity and require --trait-id.
3. Compute (prescriptive): Launch just-prs-mcp==0.3.1 with local stdio in essentials mode. Pass the resolved local path, never VCF bytes. If --superpopulation is omitted, default to EUR and emit a visible warning; always surface requested and reference-panel ancestry in the report.
4. Curate (prescriptive): For trait mode request interpret=true and profile=curated by default. Preserve the upstream filter summary and failures.
5. Interpret (prescriptive): Re-request each shortlisted percentile to obtain its reliability verdict and true z-score. Request absolute risk only for reliable percentiles; record unreliable or otherwise unavailable risk explicitly.
6. Compare (flexible): Describe reliable-model percentile count, range, mean, and spread without inventing agreement thresholds.
7. Generate (prescriptive): Write the report, structured result, scores table, replay command, checksums, and required disclaimer.

CLI Reference

uv sync --extra just-prs

uv run --extra just-prs python skills/just-prs-mcp/just_prs_mcp_bridge.py \
  --input sample.vcf.gz \
  --trait "type 2 diabetes" \
  --superpopulation EUR \
  --output output/just-prs-t2d

uv run --extra just-prs python skills/just-prs-mcp/just_prs_mcp_bridge.py \
  --input sample.vcf.gz --pgs-id PGS000014 --output output/just-prs-single

uv run --extra just-prs python skills/just-prs-mcp/just_prs_mcp_bridge.py \
  --demo --output /tmp/just_prs_demo

uv run --extra just-prs clawbio.py run just-prs --demo

Demo

Run:

uv run --extra just-prs clawbio.py run just-prs --demo

The demo is deterministic and offline. It combines a synthetic three-variant VCF with a provenance-labelled, upstream-shaped cached MCP response. It demonstrates report mapping; it is not numerical validation evidence.

Algorithm / Methodology

1. Resolve a specific ontology trait or PGS Catalog score.
2. Compute sum(effect_weight × dosage) in upstream just-prs.
3. Retain matched/total variant coverage and weight-mass coverage, C_wt.
4. Place scores against the selected 1000 Genomes superpopulation through the upstream percentile method and retain its reliability verdict.
5. Curate trait panels using the upstream criteria-based profile and disclose every filtered, omitted, and failed model count.
6. Request absolute risk only when the upstream percentile is reliable, using its z-score and upstream prevalence/effect-size evidence.
7. Compare multiple reliable models descriptively rather than selecting one convenient result.

Key parameters:

• Superpopulations: AFR, AMR, EAS, EUR, SAS (1000 Genomes).
• Default profile: curated (criteria owned by just-prs-mcp, not ClawBio).
• Default returned models: 5, ranked by the upstream coverage-aware ordering.

Example Queries

• "Compute my type 2 diabetes PRS from this GRCh38 VCF."
• "Use PGS000014 on this WGS callset and show absolute risk if available."
• "Do the reliable models agree on my coronary artery disease percentile?"

Example Output

# just-prs Polygenic Risk Report

## Model agreement
- Reliable models: **2**
- Verdict: **descriptive_spread_only**
- Reliable percentile range: **61.00–74.00**
- Descriptive percentile spread: **13.00**

## Score details
| PGS ID | Status | Percentile | Reliable | C_wt | Quality | Absolute risk |
|---|---|---:|---|---:|---|---|
| PGS000014 | scored | 74.00 | True | 94.0% | High | 18.0% |
| PGS000013 | scored | 61.00 | True | 91.0% | Normal | unavailable |

Output Structure

output_directory/
├── report.md
├── result.json
├── tables/
│   └── scores.csv
└── reproducibility/
    ├── commands.sh
    └── checksums.sha256

Dependencies

Required:

• uvx; launches the isolated Python 3.13+ upstream server.
• fastmcp in the just-prs optional extra; Python 3.11-compatible client.
• typer in the just-prs optional extra; typed CLI.

Optional:

• A warm upstream cache; avoids repeat downloads but does not change results.

The upstream cache defaults to the platform-specific just-prs cache. Override it with PRS_MCP_CACHE_DIR when a controlled shared cache is required.

Validation Evidence

• Upstream just-prs/tests/test_cross_engine.py checks numerical parity across PLINK2, Polars, and DuckDB scoring engines.
• Upstream test_scoring.py, test_vcf.py, and test_percentile.py cover scoring files, VCF/build handling, and percentile/z-score consistency.
• This bridge tests its integration boundary: pinned real stdio MCP calls, FastMCP result decoding, local-path-only requests, report mapping, routing, packaging, unreliable-risk suppression, and offline demo reproducibility.
• ClawBio does not reimplement or claim independent validation of the upstream numerical engine; it reuses that evidence and tests its own adapter behavior.

Gotchas

• You will want to treat match rate as model coverage. Do not. Here is why. Match rate counts variants equally; retain C_wt because effect-weight mass is the upstream scale-free honesty signal.
• You will want to report the highest percentile as the answer. Do not. Here is why. Multiple models can disagree because of coverage, ancestry, and model design; report the reliable-model spread and filtering provenance.
• You will want to interpret a missing absolute-risk result as average risk. Do not. Here is why. Missing prevalence or effect-size evidence means the estimate is unavailable, not normal.
• You will want to omit ancestry because EUR is the default. Do not. Here is why. Silent EUR-referenced percentiles are an equity failure mode; warn when the default is applied and name the reference-panel ancestry in the report.
• You will want to treat an empty curated row list as a failed run. Do not. Here is why. The engine may have scored models and then explicitly removed every one for weak evidence or coverage; inspect n_filtered and filter_summary so the exclusion is visible.
• Do not silently accept trait-search ambiguity; require a stable ontology ID.
• Do not interpret a build-mismatched score until the coordinate build is resolved. This is enforced, not merely advised: on build_mismatch, absolute risk is withheld and the report opens with a warning.
• Do not use a VCF fixture with sample genotypes unless it declares the GT FORMAT header; real readers correctly omit an undeclared genotype field.

Safety

• Local-first: The VCF remains on the machine. The bridge passes only its resolved path to a local stdio child process and has no upload path of its own. Note the trust boundary: uvx fetches and runs the pinned third-party just-prs-mcp package, and that process is what actually reads the genome. ClawBio performs no upload; egress is delegated to a version-pinned dependency, not eliminated.
• Credential isolation: The child receives an allow-listed runtime, network, and cache environment; unrelated API keys and service credentials are not forwarded.
• Network egress: Live runs fetch only public PGS Catalog metadata, scoring files, and reference distributions. This is a documented dependency, not a claim of zero network access. The offline demo makes no network calls.
• Consent boundary: Never switch this bridge to hosted HTTP/SSE for personal genomic data. A remote server cannot access the local path and must not receive the VCF.
• Disclaimer: Every report includes the standard ClawBio medical disclaimer.
• Audit trail: Reports record versions, input checksum, replay command, and output checksums without copying genotype content into outputs.
• No hallucinated science: Scientific calculations and curation criteria remain upstream; ClawBio maps and explains the returned evidence.

Agent Boundary

The agent dispatches, asks for ancestry/trait clarification, and explains. The skill executes scoring and evidence retrieval. The agent must not override upstream reliability, invent an absolute risk, or suppress model failures.

Integration with Bio Orchestrator

Trigger conditions:

• A VCF/WGS input plus explicit PRS, polygenic-risk, or absolute-risk intent.
• An explicit request to use just-prs on a local genome.

Chaining partners:

• wgs-prs: Produces a called VCF from raw sequencing before this skill.
• gwas-prs: Handles 23andMe/AncestryDNA text inputs instead of VCF/WGS.
• profile-report: May consume result.json in a later compatibility PR.

Maintenance

• Review cadence: Review monthly and on every just-prs-mcp release.
• Staleness signals: MCP schema drift, changed curation fields, a new just-prs coverage contract, or a PGS Catalog API change.
• Deprecation: Archive if upstream no longer supports local stdio or ClawBio adopts a generic MCP bridge with the same tested report contract.

Citations

• PGS Catalog; public score metadata and scoring files.
• just-prs; scoring, normalization, percentile, quality, and PLINK2 parity validation.
• just-prs-mcp; typed MCP contracts, curated trait workflow, and local stdio privacy boundary.
• just-dna-lite FAQ; local computation, user ownership, open access, and citizen-science context.

ClawBio is a research and educational tool. It is not a medical device and does not provide clinical diagnoses. Consult a healthcare professional before making any medical decisions.