kemal
194c087b24
- simurg/pgx/star.py: solver-free diplotype enumeration incl. CN forms (deletion, xN), wildcards, array-equivalence classes, raw_score/score with CPIC frequency priors; calibrated error model (spec PGX-012 amended). - pipeline/pgx_star.py: DB gene models, SNV + PGx CN VCF evidence, masks, diplotype_summary.tsv + pgx_calls.json. - scripts/pgx: derive_masks.py (array vs 1000G 30x over HTTPS, GS calibration), getrm_truth.py, validate_star_getrm.py. - GSA v4 PGx demo vs GeT-RM (16 CEPH): 100/109 gene calls; CYP2D6/2C19/2C9 41/45 (docs/validation/V2_pgx_star.md).
86 lines
3.7 KiB
Python
86 lines
3.7 KiB
Python
#!/usr/bin/env python3
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"""Build the PGx CN target-region BED (spec PCN-001) from UCSC ncbiRefSeq (GRCh38).
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python scripts/pgx/build_cn_regions.py ncbiRefSeq.hg38.txt.gz OUT.bed [--version N]
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Regions (0-based half-open BED: chrom start0 end region gene), from the MANE/first-listed transcript:
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CYP2D6.p5 2 kb 5' flank of CYP2D6 (upstream of exon 1; the gene is on the minus strand)
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CYP2D6.intron.2 CYP2D6 intron 2
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CYP2D6.exon.9 CYP2D6 exon 9
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CYP2A6.exon.1 CYP2A6 exon 1 (± 500 bp)
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CYP2A6.intron.7 CYP2A6 intron 7
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GSTM1, GSTT1 (on chr22_KI270879v1_alt, IN-062), UGT2B17, SULT1A1, CYP2E1: whole gene.
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Exons and introns are numbered in transcript order (strand-aware). [DB: NCBI RefSeq via UCSC ncbiRefSeq]
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"""
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from __future__ import annotations
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import argparse
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import gzip
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from pathlib import Path
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TRANSCRIPT = {"CYP2D6": "NM_000106", "CYP2A6": "NM_000762", "GSTM1": "NM_000561", "GSTT1": "NM_000853",
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"UGT2B17": "NM_001077", "SULT1A1": "NM_001055", "CYP2E1": "NM_000773"} # fmt: skip
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FLANK = 2000
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PAD = 500
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def main() -> int:
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ap = argparse.ArgumentParser(description=__doc__, formatter_class=argparse.RawDescriptionHelpFormatter)
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ap.add_argument("refseq", type=Path)
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ap.add_argument("out", type=Path)
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ap.add_argument("--version", type=int, default=1)
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a = ap.parse_args()
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tx: dict[str, tuple[str, str, list[int], list[int]]] = {}
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with gzip.open(a.refseq, "rt") as fh:
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for line in fh:
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f = line.rstrip("\n").split("\t")
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name, chrom, strand, gene = f[1], f[2], f[3], f[12]
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if gene not in TRANSCRIPT or not name.startswith(TRANSCRIPT[gene] + "."):
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continue
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if "_" in chrom and not (gene == "GSTT1" and chrom == "chr22_KI270879v1_alt"):
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continue # primary assembly, except GSTT1 which is only on the alt contig
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starts = [int(x) for x in f[9].rstrip(",").split(",")]
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ends = [int(x) for x in f[10].rstrip(",").split(",")]
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tx.setdefault(gene, (chrom, strand, starts, ends))
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missing = set(TRANSCRIPT) - set(tx)
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if missing:
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raise SystemExit(f"transcripts not found: {sorted(missing)}")
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rows: list[tuple[str, int, int, str, str]] = []
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def exon(gene: str, k: int) -> tuple[int, int]:
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_, strand, s, e = tx[gene]
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i = k - 1 if strand == "+" else len(s) - k
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return s[i], e[i]
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def intron(gene: str, k: int) -> tuple[int, int]:
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strand = tx[gene][1]
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a_, b_ = exon(gene, k), exon(gene, k + 1)
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return (a_[1], b_[0]) if strand == "+" else (b_[1], a_[0])
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for gene in ("CYP2D6", "CYP2A6"):
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chrom, strand, s, e = tx[gene]
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if gene == "CYP2D6":
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p5 = (e[-1], e[-1] + FLANK) if strand == "-" else (s[0] - FLANK, s[0])
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rows += [(chrom, *p5, "CYP2D6.p5", gene), (chrom, *intron(gene, 2), "CYP2D6.intron.2", gene),
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(chrom, *exon(gene, 9), "CYP2D6.exon.9", gene)] # fmt: skip
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else:
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x1 = exon(gene, 1)
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rows += [(chrom, x1[0] - PAD, x1[1] + PAD, "CYP2A6.exon.1", gene),
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(chrom, *intron(gene, 7), "CYP2A6.intron.7", gene)] # fmt: skip
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for gene in ("GSTM1", "GSTT1", "UGT2B17", "SULT1A1", "CYP2E1"):
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chrom, strand, s, e = tx[gene]
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rows.append((chrom, s[0], e[-1], gene, gene))
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order = {f"chr{i}": i for i in range(1, 23)}
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rows.sort(key=lambda r: (order.get(r[0].split("_")[0], 99), r[0], r[1]))
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with a.out.open("w") as fh:
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fh.write(f"# simurg PGx CN regions v{a.version}, GRCh38, from UCSC ncbiRefSeq (PCN-001)\n")
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for r in rows:
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fh.write("\t".join(map(str, r)) + "\n")
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print(a.out.read_text())
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return 0
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if __name__ == "__main__":
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raise SystemExit(main())
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