#!/usr/bin/env python3 """Validate `simurg pgx copy-number call` against the NYGC 30x SV callset (1KGP_3202 freeze V3) — PCN-017. python scripts/pgx/validate_cn_truth.py --calls CALL_DIR --identity scripts/pgx/demo36_identity.tsv \ --sv 1KGP_3202.sv_freeze_V3.vcf.gz --bcftools BCFTOOLS --out summary.json Truth per region = RD_CN of one SV record per region (below, chosen as the record spanning the whole region; for GSTM1 the read-depth DUP/CNV record, whose RD_CN gives 0/1/2 in Hardy–Weinberg proportions — the DEL record there reports CN 1 for 27/30 individuals). CYP2D6 sub-regions share one gene-level record, so exon-9 conversions (*36) and 2D7-2D6 hybrids (*13, *68) legitimately differ from it. GSTT1 lies on an alt contig with no SV calls: only its CN distribution is reported. Replicate arrays of one individual are counted once (the first array). """ from __future__ import annotations import argparse import collections import csv import json import subprocess from pathlib import Path TRUTH_RECORD = {"GSTM1": "HGSV_9691", "UGT2B17": "HGSV_63272", "SULT1A1": "HGSV_207805", "CYP2A6.intron.7": "HGSV_232737", "CYP2A6.exon.1": "HGSV_232737", "CYP2D6.exon.9": "HGSV_247317", "CYP2D6.intron.2": "HGSV_247317", "CYP2D6.p5": "HGSV_247317"} # fmt: skip def main() -> int: ap = argparse.ArgumentParser(description=__doc__, formatter_class=argparse.RawDescriptionHelpFormatter) ap.add_argument("--calls", required=True, type=Path) ap.add_argument("--identity", required=True, type=Path) ap.add_argument("--sv", required=True) ap.add_argument("--bcftools", default="bcftools") ap.add_argument("--out", required=True, type=Path) a = ap.parse_args() ident = {} with a.identity.open() as fh: for r in csv.DictReader((ln for ln in fh if not ln.startswith("#")), delimiter="\t"): ident[r["sample_id"]] = r["individual"] calls: dict[str, dict[str, str]] = {} with (a.calls / "pgx_cn_sample_summary.tsv").open() as fh: for r in csv.DictReader(fh, delimiter="\t"): ind = ident.get(r["sample_id"]) if ind and ind not in calls: calls[ind] = {k[3:]: v for k, v in r.items() if k.startswith("cn_")} ids = sorted(set(TRUTH_RECORD.values())) q = subprocess.run([a.bcftools, "query", "-H", "-s", ",".join(sorted(calls)), "--force-samples", "-i", "ID=@/dev/stdin", "-f", "%ID[\t%RD_CN]\n", a.sv], input="\n".join(ids), capture_output=True, text=True, check=True).stdout.splitlines() # fmt: skip samples = [h.split("]")[1].split(":")[0] for h in q[0].split("\t")[1:]] truth = {ln.split("\t")[0]: dict(zip(samples, ln.split("\t")[1:], strict=True)) for ln in q[1:]} res: dict[str, dict[str, object]] = {} tot = [0, 0] for region, rid in TRUTH_RECORD.items(): pairs = [(truth[rid][ind], c[region]) for ind, c in calls.items() if ind in truth.get(rid, {})] pairs = [(t, c) for t, c in pairs if t not in (".", "")] ok = sum(t == c for t, c in pairs) tot[0] += ok tot[1] += len(pairs) res[region] = {"record": rid, "concordant": ok, "n": len(pairs), "rate": round(ok / len(pairs), 4) if pairs else None, "truth_to_call_mismatches": dict(collections.Counter(f"{t}->{c}" for t, c in pairs if t != c))} # fmt: skip summary = {"individuals": len(calls), "regions": res, "overall": {"concordant": tot[0], "n": tot[1], "rate": round(tot[0] / tot[1], 4) if tot[1] else None}, "gstt1_cn_distribution": dict(sorted(collections.Counter(c.get("GSTT1", ".") for c in calls.values()).items()))} # fmt: skip a.out.write_text(json.dumps(summary, indent=1)) print(json.dumps(summary, indent=1)) return 0 if __name__ == "__main__": raise SystemExit(main())