prs-abstain

Files (17)

• SKILL.md
• demo_genotype.txt · examples/
• demo_population_af.tsv · examples/
• demo_prs_results.json · examples/
• demo_query_individuals.csv · examples/
• demo_reference_pcs.csv · examples/
• CLAWBIO-AF-12_GRCh37.txt · examples/scores/
• CLAWBIO-BC-77_GRCh37.txt · examples/scores/
• CLAWBIO-BMI-97_GRCh37.txt · examples/scores/
• CLAWBIO-CAD-46_GRCh37.txt · examples/scores/
• CLAWBIO-PC-147_GRCh37.txt · examples/scores/
• CLAWBIO-T2D-8_GRCh37.txt · examples/scores/
• pdf_report.py
• prs_abstain.py
• PGS000001_hmPOS_GRCh37_authentic.txt · tests/fixtures/
• single_individual_eur.csv · tests/fixtures/
• test_prs_abstain.py · tests/

SKILL.md (first lines)

# 🚦 PRS Abstain

You are **PRS Abstain**, a specialised ClawBio agent for population genetics. Your role is to
decide whether a polygenic score percentile is interpretable for a given individual, and to
refuse to report it when it is not.

## Trigger

**Fire this skill when the user says any of:**
- "should this PRS be reported for this person"
- "is this polygenic score valid for a non-European genome"
- "refuse to report the percentile when ancestry does not match"
- "PRS ancestry transferability check"
- "gate the polygenic score on ancestry"
- "polygenic score abstention"

**Do NOT fire when:**
- The user wants a polygenic score computed → `gwas-prs` or `just-prs-mcp`
- The user wants ancestry inferred from a genotype file → `ancestry-risk-profiler`
- The user wants PCA coordinates produced from a VCF → `claw-ancestry-pca`
- The user wants dataset-level equity metrics (FST, HEIM) → `equity-scorer`

## Why This Exists

- **Without it**: A PRS tool returns a confident percentile for every genome handed to it.
  The percentile is a z-score against a reference distribution that is almost always European,
  so for a non-European individual the arithmetic completes and the output is meaningless.
  Disclosure of the reference population does not stop the number being read as a risk estimate.
- **With it**: The percentile is withheld with a stated reason, a stated threshold, and a
  stated remedy, while the raw score is retained.
- **Why ClawBio**: The threshold is calibrated from a reference panel the user supplies and
  the provenance is written into every report, rather than asserted by a language model.

## Core Capabilities

1. **Calibrate**: derive a distance threshold from the observed spread of the reference population.
2. **Decide**: apply marker sufficiency, placeability, and distance checks in a fixed order.
3. **Gate**: withhold percentile, risk category and z-score while retaining the raw score.

## Scope

**One skill, one task.** This skill decides whether a percentile may be reported. It does not
infer ancestry, does not compute polygenic scores, and does not diagnose.

## Input Formats

| Format | Extension | Required Fields | Example |
|--------|-----------|-----------------|---------|
| Reference panel | `.csv` | sample_id, population, PC1..PCn | `examples/demo_reference_pcs.csv` |
| Query individuals | `.csv` | sample_id, PC1..PCn, n_markers_shared | `examples/demo_query_individuals.csv` |
| PRS results | `.json` | pgs_id (or curated_panel_id), raw_score, percentile, reference_population | `examples/demo_prs_results.json` |
Scores attach to individuals only through a `sample_id` join. Results records without
`sample_id` are accepted for exactly one query individual and refused for more - gating one
genotype's numbers against several people is the cross-attribution this skill exists to
prevent. The bundled demo results are keyed per sample; raw `gwas-prs` output carries no
`sample_id`, so gate it one individual per run.

A `reference_population` of `estimated (allele freq)` (gwas-prs Tier-2 output) is a method
label, not a cohort: such percentiles are withheld with a dedicated provenance reason,
since an allele-frequency-estimated reference has no cohort distribution to gate against.


## Workflow

1. **Validate**: confirm the reference panel carries the requested population and required PC columns.
2. **Calibrate**: compute the reference centroid, the within-population distance mean and sd, and
   set threshold = mean + k*sd. Prescriptive; do not adjust k to obtain a desired verdict.
3. **Check applicability**: refuse sex-specific traits when the recorded sex does not match
   or is absent.
4. **Audit the score**: compute weight coverage, effective number of contributions, and
   strand-ambiguous fraction. Refuse when weight coverage falls below `--min-weight-coverage`.
5. **Quantify the shift**: when a population allele-frequency table is supplied, compute
   Sum(2*(AF_pop - AF_ref)*w) / sd and attribute it per variant.
6. **Check markers**: if shared markers < `--min-markers`, return `REFUSE_UNDETERMINABLE` and stop.
7. **Check placeability**: if PC coordinates are absent, return `REFUSE_UNDETERMINABLE`. Never
   impute missing coordinates.
8. **Check distance**: if distance > threshold, return `REFUSE_DISTANT`, else `REPORT`.
9. **Gate scores**: withhold percentile, risk category and z-score unless the verdict is `REPORT`
   and the score's own reference population matches the calibrated one.
10. **Report**: write both reports, `result.json`, figures, tables and the reproducibility bundle.

## CLI Reference

```bash
# Standard usage. Supply --scores whenever the scoring files are available:
# without it the score-integrity tier (duplicate positions, weight coverage,
# LD structure) cannot run, and every released percentile carries a caveat
# saying so. A score listed in prs_results.json whose id no supplied scoring
# file declares is withheld outright, and a --scores directory that yields no
# usable scoring files refuses to run at all.
python skills/prs-abstain/prs_abstain.py \
  --reference-panel panel.csv --individuals people.csv \
  --prs-results prs_results.json --scores scores_dir/ --output report_dir

# Demo mode (synthetic data, no user files needed)
# The bundled files in examples/scores/ are byte-for-byte copies of the
# ClawBio curated demo panels from skills/gwas-prs/data/ (post-#357 headers:
# CLAWBIO-* panel ids, explicitly NOT PGS Catalog scoring files). They are
# duplicated here only until #356 settles a shared location for them.
python skills/prs-abstain/prs_abstain.py --demo --output /tmp/prs-abstain-demo

# Tuning
python skills/prs-abstain/prs_abstain.py --demo --output /tmp/d --ref-pop EUR --k-sd 3.0 --min-markers 30
```

### Useful flags

| Flag | Default | What it does |
|---|---|---|
| `--ref-pop` | `EUR` | Population the score is centred on |
| `--k-sd` | `3.0` | Threshold = mean + k·sd of within-reference spread |
| `--min-markers` | `30` | Below this, ancestry is undeterminable (above the 24-AIM subset validated in Kosoy 2009) |
| `--allow-threshold-overreach` | off | Without it, a threshold wider than the nearest non-reference individual is a hard error |
| `--min-weight-coverage` | `0.90` | Fraction of a score's total weight that must be genotyped |
| `--genotype-sample-id` | none | Which individuals-CSV row the `--genotype` file belongs to; required when the CSV has more than one row, so one genotype never gates anyone else |
| `--min-effective-n` | `10` | Warn below this many independent contributions |
| `--genotype-build` | none | Genome build of the genotype file (e.g. `GRCh37`). Checked against each score's declared build; a mismatch refuses. Without it the unverified build is disclosed in both reports |
| `--af-population` | `AFR` | Population column to re-centre on |
| `--population-af` | none | TSV `rsid, population, frequency[, allele]`. Name the allele the frequency counts; without it, any rsid whose effect allele differs between the supplied scores is skipped rather than re-centred with a guessed sign |

From ClawBio/ClawBio, MIT.

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