PGx validation on GSE165845: WGS-derived star truth, 2-fold masks, array-resolvable concordance

- scripts/pgx/wgs_star_truth.py: star alleles from the 1000G 30x phased panel with the DB definitions
  (wildcard-aware haplotype assignment; checked against GeT-RM on the demo CEPH individuals).
- validate_star_getrm.py: --all-genes, --individuals, --coverage (projection onto what the array can see);
  replicate_concordance.py.
- 120 individuals x 3 GSA v1 arrays: array-resolvable 1637/1710 (95.7 %), top 1223/1800 (chip lacks many
  defining variants), GeT-RM subset 28/35, replicates 99.2 % without the failed array (V2_pgx_star.md, K-029).
This commit is contained in:
kemal committed 2026-09-29 19:00:34 +01:00
1 parent 2bd9773478
commit 004739da8e
6 files changed
+4213 -1

No files matched your search

+43
View File
@@ -79,13 +79,42 @@ def main() -> int:
ap.add_argument("--truth", required=True, type=Path)
ap.add_argument("--identity", required=True, type=Path)
ap.add_argument("--out", required=True, type=Path)
ap.add_argument("--all-genes", action="store_true",
help="truth with the same definitions (wgs_star_truth.py): no legacy-name exclusions") # fmt: skip
ap.add_argument("--individuals", type=Path, help="only these individuals (one per line)")
ap.add_argument("--coverage", type=Path, help="pgx_coverage.tsv of the array: also report array-resolvable "
"concordance (both diplotypes projected onto the alleles the array can tell apart)") # fmt: skip
a = ap.parse_args()
if a.all_genes:
LEGACY_NOMENCLATURE.clear()
only = set(a.individuals.read_text().split()) if a.individuals else None
proj: dict[tuple[str, str], str] = {}
refs: dict[str, str] = {}
if a.coverage:
with a.coverage.open() as fh:
for r in csv.DictReader((ln for ln in fh if not ln.startswith("#")), delimiter="\t"):
if r["allele_kind"] == "reference":
refs[r["gene"]] = r["allele"]
st = r["status"]
proj[(r["gene"], r["allele"])] = st.split(":", 1)[1] if st.startswith("equivalent_to:") else (
r["allele"] if st == "callable" else "") # fmt: skip
def project(gene: str, allele: str) -> str:
core = re.sub(r"x\d+$|xN$", "", allele.split("+")[-1])
v = proj.get((gene, core), core)
if v:
return v
ref = refs.get(gene, core) # not covered: indistinguishable from the reference's class
return proj.get((gene, ref)) or ref
with a.identity.open() as fh:
ident = {r["sample_id"]: r["individual"] for r in csv.DictReader((ln for ln in fh if not ln.startswith("#")),
delimiter="\t")} # fmt: skip
truth: dict[tuple[str, str], str] = {}
with a.truth.open() as fh:
for r in csv.DictReader(fh, delimiter="\t"):
if r.get("flag") == "incomplete" or (only is not None and r["individual"] not in only):
continue
truth[(r["individual"], r["gene"])] = r["diplotype"]
calls = json.loads(a.calls.read_text())
per_gene: dict[str, dict[str, int]] = defaultdict(lambda: defaultdict(int))
@@ -135,11 +164,21 @@ def main() -> int:
if len(e.split("/")) >= 2) # fmt: skip
st["top"] += ok_top
st["equivalent"] += ok_eq
if a.coverage and len(top) == 2 and len(opts) == 1 and all(len(x) == 1 for x in opts[0]):
tt = sorted(project(g["gene"], next(iter(x))) for x in opts[0])
cc = sorted(project(g["gene"], x) for x in top)
st["array_resolvable_n"] += 1
st["array_resolvable"] += tt == cc
if not ok_top:
detail.append({"individual": ind, "gene": g["gene"], "truth": t, "call": g["genotype"],
"within_equivalents": ok_eq}) # fmt: skip
comparable = {k: v for k, v in per_gene.items() if k not in LEGACY_NOMENCLATURE}
tot_ar = [
sum(v.get("array_resolvable", 0) for v in comparable.values()),
sum(v.get("array_resolvable_n", 0) for v in comparable.values()),
]
summary = {"individuals": len(seen), "genes": {k: dict(v) for k, v in sorted(per_gene.items())},
"array_resolvable_total": {"concordant": tot_ar[0], "n": tot_ar[1]},
"legacy_nomenclature_genes": sorted(LEGACY_NOMENCLATURE),
"total": {k: sum(v.get(k, 0) for v in comparable.values()) for k in ("n", "top", "equivalent")},
"discordant": detail} # fmt: skip
@@ -147,8 +186,12 @@ def main() -> int:
for g, v in sorted(per_gene.items()):
print(f"{g:8s} top {v['top']}/{v['n']} within equivalents {v['equivalent']}/{v['n']}"
+ (f" (not comparable {v['not_comparable']})" if v.get("not_comparable") else "")
+ (f" array-resolvable {v.get('array_resolvable', 0)}/{v.get('array_resolvable_n', 0)}"
if a.coverage else "")
+ (" [legacy nomenclature]" if g in LEGACY_NOMENCLATURE else "")) # fmt: skip
print("total (excluding legacy-nomenclature genes)", summary["total"])
if a.coverage:
print("array-resolvable total", summary["array_resolvable_total"])
return 0