a56d88e05670b759ff3b32829542537ccc790c57 lrnassar Tue Apr 28 19:18:20 2026 -0700 Address CR feedback on insight + tp53 hub scripts. refs #37418 Drop duplicated bash() wrappers in favor of subprocess.run / check_output with list args, eliminating shell=True, embedded-quote concerns, and stderr-into-stdout merging. Centralize common operations as run_sort_bed/run_liftOver in tp53FuncLib alongside existing run_bedToBigBed. Switch HTML escaping to stdlib html.escape() consistently. insightHCIPriors mouseover (previously unescaped) now escapes HGVS fields, addressing the specific c.123A>G case Jonathan flagged. Replace invalid </br> tags with <br> across all five affected mouseover sites. diff --git src/hg/makeDb/scripts/tp53/tp53PVS1Splice.py src/hg/makeDb/scripts/tp53/tp53PVS1Splice.py index 8403d0b88e5..841004e8e93 100644 --- src/hg/makeDb/scripts/tp53/tp53PVS1Splice.py +++ src/hg/makeDb/scripts/tp53/tp53PVS1Splice.py @@ -1,219 +1,219 @@ #!/usr/bin/env python3 """ TP53 VCEP PVS1 Splice Sites subtrack (under PVS1 Evidence composite). Parses Supplementary Table S1 (1,061 rows) from the CSpec GN009 v2.4.0 splicing worksheet. Extracts the 120 canonical +/- 1,2 splice-site SNVs, forward-fills PVS1 strength assignments from the anchor variant to its two sibling variants at the same position, and emits bigBed 9+6. Transcript: NM_000546.6 (chr17 minus strand). """ import argparse import os import re import sys import openpyxl sys.path.insert(0, os.path.dirname(os.path.abspath(__file__))) import tp53FuncLib as lib DEFAULT_OUTDIR = "/hive/users/lrnassar/claude/RM37399/pvs1Splice" DEFAULT_SRC = "/hive/users/lrnassar/claude/RM37399/tp53_downloads/splicing_worksheet.xlsx" VAR_RE = re.compile(r'^c\.(-?\d+)([+-])([12])([ACGT])>([ACGT])$') # (color, points, acmg_for_display). RNA-variants use same color as canonical. STRENGTH_MAP = { "PVS1": ("180,0,0", "+8", "PVS1"), "PVS1 (RNA)": ("180,0,0", "+8", "PVS1 (RNA)"), "PVS1_Strong": ("210,0,0", "+4", "PVS1_Strong"), "PVS1_Strong (RNA)": ("210,0,0", "+4", "PVS1_Strong (RNA)"), "PVS1_Moderate": ("204,102,0","+2", "PVS1_Moderate"), "PVS1_Moderate (RNA)":("204,102,0","+2", "PVS1_Moderate (RNA)"), "PVS1_N/A": ("128,128,128","0", "PVS1_N/A"), } UNASSIGNED = ("200,200,200", "0", "Not yet assigned by VCEP") AUTOSQL = """table TP53PVS1Splice "TP53 VCEP PVS1 splice-site variants (+/- 1,2) from CSpec GN009 v2.4.0 Table S1" ( string chrom; "Reference sequence chromosome or scaffold" uint chromStart; "Start position in chromosome" uint chromEnd; "End position in chromosome" string name; "HGVSc variant" uint score; "Not used, all 0" char[1] strand; "Not used, all ." uint thickStart; "Same as chromStart" uint thickEnd; "Same as chromEnd" uint reserved; "RGB color" string acmgCode; "VCEP-assigned PVS1 strength" string points; "Tavtigian points" string assignSource; "'Assigned' or 'Inherited from site anchor'" lstring rationale; "VCEP rationale text (from Table S1)" uint exonNum; "mRNA exon number" lstring _mouseOver; "HTML mouseover" ) """ def cdna_splice_to_genomic(exon_num, sign, offset, tx): """Return BED (g_start, g_end) for a canonical +/-1/+/-2 splice variant.""" n_exons = len(tx['exonStarts']) if tx['strand'] == '-': idx = n_exons - exon_num else: idx = exon_num - 1 ex_g_start = tx['exonStarts'][idx] ex_g_end = tx['exonEnds'][idx] if tx['strand'] == '-': if sign == '+': g = ex_g_start - offset else: g = ex_g_end + offset - 1 else: if sign == '+': g = ex_g_end + offset - 1 else: g = ex_g_start - offset return (g, g + 1) def load_variants(src_xlsx): wb = openpyxl.load_workbook(src_xlsx, data_only=True) ws = wb["Table S1"] variants = [] for row in ws.iter_rows(min_row=4, values_only=True): if row[0] is None or not row[2] or not isinstance(row[2], str): continue m = VAR_RE.match(row[2].strip()) if not m: continue variants.append({ 'exon': int(row[0]), 'variant': row[2].strip(), 'c_pos': int(m.group(1)), 'sign': m.group(2), 'offset': int(m.group(3)), 'ref': m.group(4), 'alt': m.group(5), 'pvs1_raw': row[15], 'rationale_raw': row[16], }) # Forward-fill within each splice-site position by_site = {} for v in variants: key = (v['c_pos'], v['sign'], v['offset']) by_site.setdefault(key, []).append(v) for _key, vs in by_site.items(): anchor_pvs1 = next((x['pvs1_raw'] for x in vs if x['pvs1_raw']), None) anchor_rat = next((x['rationale_raw'] for x in vs if x['rationale_raw']), None) for x in vs: if x['pvs1_raw']: x['final_pvs1'] = x['pvs1_raw'] x['final_rat'] = x['rationale_raw'] or anchor_rat x['assign_source'] = "Assigned" elif anchor_pvs1: x['final_pvs1'] = anchor_pvs1 x['final_rat'] = anchor_rat x['assign_source'] = "Inherited from site anchor" else: x['final_pvs1'] = None x['final_rat'] = None x['assign_source'] = "Not yet assigned" return variants def mouseover(v, color, pts, acmg): # Build rationale line: assigned variants should not say "not explicitly # assigned" just because the rationale cell is blank. if v['final_rat']: rat_text = v['final_rat'] elif v['final_pvs1']: rat_text = ("VCEP-assigned strength; detailed rationale not populated " "in Table S1 for this position.") else: rat_text = "VCEP has not explicitly assigned a strength for this splice site." return lib.html_ascii_safe(( "<b>PVS1 splice-site variant:</b> {name} ({pts} pts)" "<br><b>ACMG code:</b> {acmg}" "<br><b>Exon:</b> {exon} ({sign_label})" "<br><b>Assignment:</b> {src}" "<br><b>VCEP rationale:</b> {rat}" "<br><b>Source:</b> CSpec GN009 v2.4.0 Supplementary Table S1" ).format( name=v['variant'], pts=pts, acmg=acmg, exon=v['exon'], sign_label="donor ({}{})".format(v['sign'], v['offset']) if v['sign'] == '+' else "acceptor ({}{})".format(v['sign'], v['offset']), src=v['assign_source'], rat=rat_text, )) def generate_bed(variants, tx): lines = [] chrom = tx['chrom'] for v in variants: try: g_start, g_end = cdna_splice_to_genomic(v['exon'], v['sign'], v['offset'], tx) except IndexError: continue if g_start >= g_end: continue final = v['final_pvs1'] if final and final in STRENGTH_MAP: color, pts, acmg = STRENGTH_MAP[final] else: color, pts, acmg = UNASSIGNED lines.append("\t".join([ chrom, str(g_start), str(g_end), v['variant'], "0", ".", str(g_start), str(g_end), color, acmg, pts, v['assign_source'], lib.html_ascii_safe(v['final_rat'] or ""), str(v['exon']), mouseover(v, color, pts, acmg), ])) return lines def build(db, outdir, src_xlsx): print("=== {} ===".format(db)) os.makedirs(outdir, exist_ok=True) tx = lib.get_transcript_info(db) variants = load_variants(src_xlsx) print(" {} splice variants parsed".format(len(variants))) from collections import Counter dist = Counter(v['final_pvs1'] or "Unassigned" for v in variants) print(" Strength distribution:") for k, n in dist.most_common(): print(" {}: {}".format(k, n)) bed_lines = generate_bed(variants, tx) print(" {} BED rows".format(len(bed_lines))) as_file = os.path.join(outdir, "TP53PVS1Splice.as") lib.write_autosql(as_file, AUTOSQL) bed = os.path.join(outdir, "TP53PVS1Splice_{}.bed".format(db)) with open(bed, 'w') as f: f.write("\n".join(bed_lines) + "\n") - lib.bash("sort -k1,1 -k2,2n {0} -o {0}".format(bed)) + lib.run_sort_bed(bed) bb = os.path.join(outdir, "TP53PVS1Splice{}.bb".format(db.capitalize())) lib.run_bedToBigBed(bed, as_file, bb, lib.chrom_sizes_path(db), "bed9+6") print(" wrote {}".format(bb)) def main(): p = argparse.ArgumentParser(description=__doc__) p.add_argument('-o', '--output-dir', default=DEFAULT_OUTDIR) p.add_argument('--db', action='append', help='hg38 or hg19 (repeat). Default hg38.') p.add_argument('--src', default=DEFAULT_SRC, help='Source XLSX (Table S1)') args = p.parse_args() dbs = args.db if args.db else ['hg38'] for db in dbs: build(db, args.output_dir, args.src) if __name__ == "__main__": main()