def main(ARGS=None):
if ARGS == None:
ARGS = sys.argv[1:]
args = parse_args(ARGS)
"""
convert certain comma delim str args to lists
"""
args.qual_impacts = str_none_split(args.qual_impacts, ",")
args.max_impact_csqs = str_none_split(args.max_impact_csqs, ",")
args.max_csq_scores = str_none_split(args.max_csq_scores, ",")
args.min_csq_scores = str_none_split(args.min_csq_scores, ",")
"""
convert all comma delim args to list, or leave as none.
"""
args_str_none = ("filter_include", "af_max_fields",
"vcf_info_flags_exclude")
for arg in args_str_none:
args.__dict__[arg] = misc.str_none_split(args.__dict__[arg], ",")
"""
read samples from fam file, send basic stats to stdout
"""
samples_i = samples.Samples(args.in_fam)
samples_i.print_stats()
"""
get all trios from samples with male proband
"""
male_trios = {}
for iid in samples_i.trios:
if samples_i.samples[iid].gender == "M":
male_trios[iid] = samples_i.samples[iid]
if len(male_trios) == 0:
print("ERROR" + \
"Can't do hemizygous screen if no " + \
"trios with male proband in cohort.")
sys.exit(1)
"""
read cnds files
"""
var_cnds = None
iid_cnds = None
pid_cnds = None
mid_cnds = None
if args.variant_cnds != None: var_cnds = VcfCnds(args.variant_cnds)
if args.iid_cnds != None: iid_cnds = VcfCnds(args.iid_cnds)
if args.pid_cnds != None: pid_cnds = VcfCnds(args.pid_cnds)
if args.mid_cnds != None: mid_cnds = VcfCnds(args.mid_cnds)
"""
init cyvcf2 VCF obj, get info subfields, header for output
"""
vcf = cyvcf2.VCF(args.in_vcf, strict_gt=True, gts012=True)
cyvcf2_vcf = Cyvcf2Vcf(vcf)
cyvcf2_vcf.get_info_subfields()
cyvcf2_vcf.get_csq_keys(spliton="Format: ", delim="|")
vcf_header_str = cyvcf2_vcf.header_to_list(
gt_varnames=GT_VARNAMES,
max_impact=args.max_impact,
max_impact_csqs=args.max_impact_csqs,
max_csq_scores=args.max_csq_scores,
min_csq_scores=args.min_csq_scores,
delim="\t")
"""
create sample idx
"""
samples_i.get_vcf_idx(vcf.samples)
"""
get case, control idxs
"""
case_idxs = [samples_i.samples[x].idx for x in samples_i.cases]
ctrl_idxs = [samples_i.samples[x].idx for x in samples_i.ctrls]
"""
iterate through all variants, performing newlyhemizygous screen on each one
"""
hemi_counts = defaultdict(int)
prev_chrom = None
linenum = 0
"""
init output file
"""
init_out_file(args.out_tsv,
force_overwrite=args.force_overwrite,
init_line=vcf_header_str + "\n")
"""
only parse X chromosome, since this is only place where hemi vars can happen
"""
for vcf_variant in cyvcf2_vcf.cyvcf2_vcf(args.x_chrom_interval):
"""
assume single allele per site, exclude sites with call as '*'
"""
alt = vcf_variant.ALT[0]
if alt == '*': continue
"""
create new Cyvcf2Variant instance
"""
cyvcf2_variant = Cyvcf2Variant(vcf_variant)
## if no qualifying impact str found in CSQ, skip
if args.qual_impacts != None:
res = cyvcf2_variant.qual_impacts_screen(args.qual_impacts,
csq_subfield="CSQ")
if res == False: continue
## if desired, derive max impact annots from var, along with other
## user defined max or min scores in CSQ for variant
csqs_maximpact_list = []
max_csq_scores = []
min_csq_scores = []
if args.max_impact == True:
cyvcf2_variant.get_annot_txs(cyvcf2_vcf.csq_keys,
csq_subfield="CSQ")
res = cyvcf2_variant.maxmin_csqs(
max_impact_csqs=args.max_impact_csqs,
max_csq_scores=args.max_csq_scores,
min_csq_scores=args.min_csq_scores,
impact_subfield="IMPACT")
(csqs_maximpact_list, max_csq_scores, min_csq_scores) = res
## filter on internal ctrl-only maf, can't do in var cnds file
if args.internal_ctrl_af_max != None:
ctrl_af = cyvcf2_variant.compute_maf(ctrl_idxs)
if ctrl_af > args.internal_ctrl_af_max:
continue
## variant cnds file provided, filter exclusively on that
if var_cnds != None:
if var_cnds.test_variant(vcf_variant) == False: continue
## otherwise, filter on user args
else:
var_pass = screens.variant_screen(
vcf_variant,
min_qual=args.min_qual,
filter_include=args.filter_include,
vcf_info_flags_exclude=args.vcf_info_flags_exclude,
internal_af_max=args.internal_af_max,
af_max=args.af_max,
af_max_fields=args.af_max_fields)
if var_pass == False: continue
hemi_carriers = set()
if iid_cnds != None and pid_cnds != None and mid_cnds != None:
for iid in male_trios:
pid = samples_i.samples[iid].pid
mid = samples_i.samples[iid].mid
iid_idx = samples_i.samples[iid].idx
pid_idx = samples_i.samples[pid].idx
mid_idx = samples_i.samples[mid].idx
trio_idxs = (iid_idx, mid_idx)
## is iid hemi at site?
trio_gts = ([vcf_variant.gt_types[id_x] for id_x in trio_idxs])
if trio_gts[0] not in set([1, 2]): continue
## is father hom ref at site?
if trio_gts[1] not in set([0]): continue
## is mother het at site?
if trio_gts[2] not in set([1]): continue
## test if proband and parents pass conditions in proband and parent
## cnds files, respectively
if iid_cnds.test_gt(vcf_variant, iid_idx) == False: continue
if pid_cnds.test_gt(vcf_variant, pid_idx) == False: continue
if mid_cnds.test_gt(vcf_variant, mid_idx) == False: continue
hemi_carriers.add(iid)
else:
hemi_screen = screens.hemi_screen
hemi_carriers = hemi_screen(vcf_variant,
samples_i,
male_trios,
min_coverage=args.min_coverage,
iid_min_perc_alt=args.iid_min_perc_alt,
pid_max_perc_alt=args.pid_max_perc_alt,
mid_min_perc_alt=args.mid_min_perc_alt,
iid_het_phredmax=args.iid_het_phredmax,
pid_hom_phredmax=args.pid_hom_phredmax,
mid_het_phredmax=args.mid_het_phredmax,
iid_hom_phredmin=args.iid_hom_phredmin,
pid_het_phredmin=args.pid_het_phredmin,
mid_hom_phredmin=args.mid_hom_phredmin)
if len(hemi_carriers) > 0:
iids = list(hemi_carriers)
for iid in iids:
samples_i.samples[iid].varcounts["newlyhemi"] += 1
outs = cyvcf2_variant.variant_to_list(
vcf_variant,
samples_i,
hemi_carriers,
cyvcf2_vcf.info_subfields,
GT_VARNAMES,
csqs_maximpact=csqs_maximpact_list,
max_csq_scores=max_csq_scores,
min_csq_scores=min_csq_scores,
delim="\t")
for out in outs:
append_out_file(args.out_tsv, out)
vcf.close()
print("Screening of VCF for newly hemizygous variants complete.")
samples_i.print_varcount_stats(var_types=["newlyhemi"])
return
def main(ARGS = None):
if ARGS == None:
ARGS = sys.argv[1:]
args = parse_args(ARGS)
"""
convert certain comma delim str args to lists
"""
args.qual_impacts = misc.str_none_split(args.qual_impacts, ",")
args.max_impact_csqs = misc.str_none_split(args.max_impact_csqs, ",")
args.max_csq_scores = misc.str_none_split(args.max_csq_scores, ",")
args.min_csq_scores = misc.str_none_split(args.min_csq_scores, ",")
"""
read samples from fam file, send basic stats to stdout
"""
samples_i = Samples(args.in_fam)
samples_i.print_stats()
n_samples = len(samples_i.samples)
n_males = len(samples_i.males)
n_females = len(samples_i.females)
n_cases = len(samples_i.cases)
n_ctrls = len(samples_i.ctrls)
"""
read cnds files
"""
var_cnds = None
pro_cnds = None
par_cnds = None
if args.variant_cnds != None: var_cnds = VcfCnds(args.variant_cnds)
if args.pro_cnds != None: pro_cnds = VcfCnds(args.pro_cnds)
if args.par_cnds != None: par_cnds = VcfCnds(args.par_cnds)
"""
init cyvcf2 VCF obj, get info subfields, header for output
"""
vcf = cyvcf2.VCF(args.in_vcf, strict_gt=True, gts012=True)
cyvcf2_vcf = Cyvcf2Vcf(vcf)
cyvcf2_vcf.get_info_subfields()
cyvcf2_vcf.get_csq_keys(spliton="Format: ", delim="|")
vcf_header_str = cyvcf2_vcf.header_to_list(gt_varnames=GT_VARNAMES,
max_impact=args.max_impact,
max_impact_csqs=args.max_impact_csqs,
max_csq_scores=args.max_csq_scores,
min_csq_scores=args.min_csq_scores,
delim="\t")
"""
create sample idx
"""
samples_i.get_vcf_idx(vcf.samples)
"""
get case, control idxs
"""
case_idxs = [samples_i.samples[x].idx for x in samples_i.cases]
ctrl_idxs = [samples_i.samples[x].idx for x in samples_i.ctrls]
"""
iterate through all variants, performing de novo screen on each one
"""
hom_counts = defaultdict(int)
prev_chrom = None
linenum=0
"""
if intervals provided, make sure to parse over those, else whole vcf
"""
if args.intervals != None:
if os.path.isfile(args.intervals):
intervals = open(args.intervals, "r").readlines()
intervals = [x.rstrip() for x in intervals]
else:
intervals = [args.intervals]
else:
intervals = [""]
"""
init output file
"""
misc.init_out_file(args.out_tsv,
force_overwrite = args.force_overwrite,
init_line = vcf_header_str)
"""
parse VCF file looking for de novo variant calls
"""
for vcf_variant in cyvcf2_vcf.iterator(intervals):
linenum+=1
#if linenum == 1000000: break
if vcf_variant.CHROM != prev_chrom:
print("Extracting newly homozygous vars from chrom " + vcf_variant.CHROM)
prev_chrom = vcf_variant.CHROM
"""
create new Cyvcf2Variant instance
"""
cyvcf2_variant=Cyvcf2Variant(vcf_variant)
"""
assume single alternate allele per row, exclude sites with call as '*'
since these are by-product of multi-sample calling and don't really
represent a real SNV/indel
"""
alt = vcf_variant.ALT[0]
if alt == '*': continue
## if no qualifying impact str found in CSQ, skip
if args.qual_impacts != None:
res = cyvcf2_variant.qual_impacts_screen(args.qual_impacts,
csq_subfield="CSQ")
if res == False: continue
## if desired, derive max impact annots from var, along with other
## user defined max or min scores in CSQ for variant
csqs_maximpact_list = []
max_csq_scores = []
min_csq_scores = []
if args.max_impact == True:
cyvcf2_variant.get_annot_txs(cyvcf2_vcf.csq_keys,
csq_subfield="CSQ")
res=cyvcf2_variant.maxmin_csqs(max_impact_csqs=args.max_impact_csqs,
max_csq_scores=args.max_csq_scores,
min_csq_scores=args.min_csq_scores,
impact_subfield="IMPACT")
(csqs_maximpact_list, max_csq_scores, min_csq_scores) = res
## filter on internal ctrl-only maf, can't do in var cnds file
if args.internal_ctrl_af_max != None:
ctrl_af = cyvcf2_variant.compute_maf(ctrl_idxs)
if ctrl_af > args.internal_ctrl_af_max:
continue
## variant cnds file provided, filter exclusively on that
if var_cnds != None:
if var_cnds.test_variant(vcf_variant) == False: continue
## otherwise, filter on user args
else:
## filter on FILTER column, default is PASS only, allow for
## user defined FILTER classifs too
if args.filter_include == None and vcf_variant.FILTER != None:
continue
elif args.filter_include != None and vcf_variant.FILTER != None:
filter_include = set(",".split(args.filter_include))
if vcf_variant not in filter_include: continue
## filter on user-defined VCF INFO flags
if args.vcf_info_flags_exclude != None:
vcf_info_flags_fail = False
for vcf_info_flag in args.vcf_info_flags_exclude.split(","):
if vcf_variant.INFO.get(vcf_info_flag) == True:
vcf_info_flags_fail = True
break
if vcf_info_flags_fail == True: continue
## filter on user-defined maximum internal MAF
if args.internal_af_max != None:
if vcf_variant.INFO.get("AF") > args.internal_af_max:
continue
## filter on user-defined maximum external MAF
if args.af_max_fields != None and args.af_max != None:
af_max_fields = args.af_max_fields.split(",")
af_max_fail = False
for af_max_field in af_max_fields:
af = vcf_variant.INFO.get(af_max_field)
if af > args.af_max:
af_max_fail=True
break
if af_max_fail == True: continue
hom_carriers = set()
if pro_cnds != None and par_cnds != None:
hom_carriers = set()
for iid in samples_i.trios:
pid = samples_i.trios[iid].pid
mid = samples_i.trios[iid].mid
iid_idx=samples_i.samples[iid].idx
pid_idx=samples_i.samples[pid].idx
mid_idx=samples_i.samples[mid].idx
trio_idxs=(iid_idx,pid_idx,mid_idx)
## is iid hom alt at site?
trio_gts = ([vcf_variant.gt_types[id_x] for id_x in trio_idxs])
if trio_gts[0] != 2:
continue
## is either parent sample hom alt at site?
if trio_gts[1] != 1 or trio_gts[2] != 1:
continue
## test if proband and parents pass conditions in proband and parent
## cnds files, respectively
if pro_cnds.test_gt(vcf_variant, iid_idx) == False: continue
if par_cnds.test_gt(vcf_variant, pid_idx) == False: continue
if par_cnds.test_gt(vcf_variant, mid_idx) == False: continue
hom_carriers.add(iid)
else:
hom_screen = screens.hom_screen
hom_carriers = hom_screen(vcf_variant, samples_i,
min_coverage = args.min_coverage,
pro_min_perc_alt=args.pro_min_perc_alt,
par_max_perc_alt=args.par_max_perc_alt,
pro_homref_phredmin=args.pro_homref_phredmin,
pro_het_phredmin=args.pro_het_phredmin,
pro_homalt_phredmax=args.pro_homalt_phredmax,
par_homref_phredmin=args.par_homref_phredmin,
par_het_phredmax=args.par_het_phredmax,
par_homalt_phredmin=args.par_homalt_phredmin)
if len(hom_carriers) > 0:
iids = list(hom_carriers)
for iid in iids:
samples_i.samples[iid].varcounts["hom"] += 1
outs = cyvcf2_variant.variant_to_list(samples_i,
hom_carriers,
cyvcf2_vcf.info_subfields,
GT_VARNAMES,
csqs_maximpact=csqs_maximpact_list,
max_csq_scores=max_csq_scores,
min_csq_scores=min_csq_scores,
delim="\t")
for out in outs:
misc.append_out_file(args.out_tsv, out)
vcf.close()
samples_i.print_varcount_stats(var_types=["hom"])
return
def main(ARGS = None):
if ARGS == None:
ARGS = sys.argv[1:]
args = parse_args(ARGS)
"""
set name of gt class
"""
gt_class = "het_trans"
if args.ntrans == True: gt_class = "het_ntrans"
"""
convert certain comma delim str args to lists
"""
args.qual_impacts = misc.str_none_split(args.qual_impacts, ",")
args.max_impact_csqs = misc.str_none_split(args.max_impact_csqs, ",")
args.max_csq_scores = misc.str_none_split(args.max_csq_scores, ",")
args.min_csq_scores = misc.str_none_split(args.min_csq_scores, ",")
"""
read samples from fam file, send basic stats to stdout
"""
samples_i = Samples(args.in_fam)
samples_i.print_stats()
n_samples = len(samples_i.samples)
n_males = len(samples_i.males)
n_females = len(samples_i.females)
n_cases = len(samples_i.cases)
n_ctrls = len(samples_i.ctrls)
"""
read cnds files
"""
var_cnds = None
pro_cnds = None
transpar_cnds = None
ntranspar_cnds = None
if args.variant_cnds != None: var_cnds = VcfCnds(args.variant_cnds)
if args.pro_cnds != None: pro_cnds = VcfCnds(args.pro_cnds)
if args.transpar_cnds != None: transpar_cnds = VcfCnds(args.transpar_cnds)
if args.ntranspar_cnds != None: ntranspar_cnds = VcfCnds(args.ntranspar_cnds)
"""
init cyvcf2 VCF obj, get info subfields, header for output
"""
vcf = cyvcf2.VCF(args.in_vcf, strict_gt=True, gts012=True)
cyvcf2_vcf = Cyvcf2Vcf(vcf)
cyvcf2_vcf.get_info_subfields()
cyvcf2_vcf.get_csq_keys(spliton="Format: ", delim="|")
vcf_header_str = cyvcf2_vcf.header_to_list(main_fields=["PAR_IID","PRO_IID","CHROM",
"POS","ID","REF","ALT",
"QUAL","FILTER"],
gt_varnames=GT_VARNAMES,
max_impact=args.max_impact,
max_impact_csqs=args.max_impact_csqs,
max_csq_scores=args.max_csq_scores,
min_csq_scores=args.min_csq_scores,
delim="\t")
"""
create sample idx
"""
samples_i.get_vcf_idx(vcf.samples)
"""
get case, control idxs
"""
case_idxs = [samples_i.samples[x].idx for x in samples_i.cases]
ctrl_idxs = [samples_i.samples[x].idx for x in samples_i.ctrls]
"""
iterate through all variants, performing de novo screen on each one
"""
trans_counts = defaultdict(int)
prev_chrom = None
linenum=0
"""
if intervals provided, make sure to parse over those, else whole vcf
"""
if args.intervals != None:
if os.path.isfile(args.intervals):
intervals = open(args.intervals, "r").readlines()
intervals = [x.rstrip() for x in intervals]
else:
intervals = [args.intervals]
else:
intervals = [""]
"""
init output file
"""
misc.init_out_file(args.out_tsv,
force_overwrite = args.force_overwrite,
init_line = vcf_header_str)
"""
parse VCF file looking for de novo variant calls
"""
for vcf_variant in cyvcf2_vcf.iterator(intervals):
linenum+=1
#if linenum == 1000000: break
if vcf_variant.CHROM != prev_chrom:
print("Extracting " + gt_class + " from chrom " + vcf_variant.CHROM)
prev_chrom = vcf_variant.CHROM
"""
assume single allele per site, exclude sites with call as '*'
"""
alt = vcf_variant.ALT[0]
if alt == '*': continue
"""
create new Cyvcf2Variant instance
"""
cyvcf2_variant=Cyvcf2Variant(vcf_variant)
## if no qualifying impact str found in CSQ, skip
if args.qual_impacts != None:
res = cyvcf2_variant.qual_impacts_screen(args.qual_impacts,
csq_subfield="CSQ")
if res == False: continue
## if desired, derive max impact annots from var, along with other
## user defined max or min scores in CSQ for variant
csqs_maximpact_list = []
max_csq_scores = []
min_csq_scores = []
if args.max_impact == True:
cyvcf2_variant.get_annot_txs(cyvcf2_vcf.csq_keys,
csq_subfield="CSQ")
res=cyvcf2_variant.maxmin_csqs(max_impact_csqs=args.max_impact_csqs,
max_csq_scores=args.max_csq_scores,
min_csq_scores=args.min_csq_scores,
impact_subfield="IMPACT")
(csqs_maximpact_list, max_csq_scores, min_csq_scores) = res
## filter on internal ctrl-only maf, can't do in var cnds file
if args.internal_ctrl_af_max != None:
ctrl_af = cyvcf2_variant.compute_maf(ctrl_idxs)
if ctrl_af > args.internal_ctrl_af_max:
continue
## variant cnds file provided, filter exclusively on that
if var_cnds != None:
if var_cnds.test_variant(vcf_variant) == False: continue
## otherwise, filter on user args
else:
## filter on FILTER column, default is PASS only, allow for
## user defined FILTER classifs too
if args.filter_include == None and vcf_variant.FILTER != None:
continue
elif args.filter_include != None and vcf_variant.FILTER != None:
filter_include = set(",".split(args.filter_include))
if vcf_variant not in filter_include: continue
## filter on user-defined VCF INFO flags
if args.vcf_info_flags_exclude != None:
vcf_info_flags_fail = False
for vcf_info_flag in args.vcf_info_flags_exclude.split(","):
if vcf_variant.INFO.get(vcf_info_flag) == True:
vcf_info_flags_fail = True
break
if vcf_info_flags_fail == True: continue
## filter on user-defined maximum internal MAF
if args.internal_af_max != None:
if vcf_variant.INFO.get("AF") > args.internal_af_max:
continue
## filter on user-defined maximum external MAF
if args.af_max_fields != None and args.af_max != None:
af_max_fields = args.af_max_fields.split(",")
af_max_fail = False
for af_max_field in af_max_fields:
af = vcf_variant.INFO.get(af_max_field)
if af > args.af_max:
af_max_fail=True
break
if af_max_fail == True: continue
trans_carriers = set()
if pro_cnds != None and transpar_cnds != None and ntranspar_cnds != None:
for iid in samples_i.trios:
pid = samples_i.trios[iid].pid
mid = samples_i.trios[iid].mid
iid_idx=samples_i.samples[iid].idx
pid_idx=samples_i.samples[pid].idx
mid_idx=samples_i.samples[mid].idx
trio_idxs=(iid_idx,pid_idx,mid_idx)
## get trio gts
trio_gts = ([vcf_variant.gt_types[id_x] for id_x in trio_idxs])
## parent with higher % alt reads is transpar,
## other parent is ntranspar
pid_alt_freq = vcf_variant.gt_alt_freqs[pid_idx]
mid_alt_freq = vcf_variant.gt_alt_freqs[mid_idx]
if pid_alt_freq > mid_alt_freq:
transpar = pid
transpar_idx = pid_idx
transpar_gt = trio_gts[1]
ntranspar = mid
ntranspar_idx = mid_idx
ntranspar_gt = trio_gts[2]
else:
transpar = mid
transpar_idx = mid_idx
transpar_gt = trio_gts[2]
ntranspar = pid
ntranspar_idx = pid_idx
ntranspar_gt = trio_gts[1]
## is more likely transmitting parent GT equal to 1?
if transpar_gt not in set([1]): continue
## is likely transmitting parent GT equal to 0?
if ntranspar_gt not in set([0]): continue
## if looking at trans variants, keep if pro is het at site
## if looking at ntnrans variant, keep if pro i homref at site
if args.ntrans == False:
if trio_gts[0] not in set([1]): continue
else:
if trio_gts[0] not in set([0]): continue
## test if proband passes conditions in proband cnds file
if pro_cnds.test_gt(vcf_variant, iid_idx) == False: continue
## test if more likely transmitting parent passes conditions
## in transpar cnds file
if transpar_cnds.test_gt(vcf_variant, transpar_idx) == False:
continue
## test if less likely transmitting parent passes conditions
## in ntranspar cnds file
if ntranspar_cnds.test_gt(vcf_variant, ntranspar_idx) == False:
continue
trans_carriers.add((transpar, iid))
else:
trans_screen = screens.trans_screen
res = trans_screen(vcf_variant, samples_i, ntrans=args.ntrans,
transpar_gts=set([1]), ntranspar_gts=set([0]),
min_coverage=args.min_coverage,
pro_min_perc_alt=args.pro_min_perc_alt,
pro_max_perc_alt=args.pro_max_perc_alt,
transpar_min_perc_alt=args.transpar_min_perc_alt,
transpar_max_perc_alt=args.transpar_max_perc_alt,
ntranspar_max_perc_alt=args.ntranspar_max_perc_alt,
pro_homref_phredmin=args.pro_homref_phredmin,
pro_het_phredmax=args.pro_het_phredmax,
pro_homalt_phredmin=args.pro_homalt_phredmin)
trans_carriers = res
if len(trans_carriers) > 0:
transpars_iids = list(trans_carriers)
for pair in trans_carriers:
transpar = pair[0]
iid = pair[1]
samples_i.samples[iid].varcounts[gt_class] += 1
outs = cyvcf2_variant.variant_to_list(samples_i,
trans_carriers,
cyvcf2_vcf.info_subfields,
GT_VARNAMES,
csqs_maximpact=csqs_maximpact_list,
max_csq_scores=max_csq_scores,
min_csq_scores=min_csq_scores,
delim="\t")
for out in outs:
misc.append_out_file(args.out_tsv, out)
vcf.close()
samples_i.print_varcount_stats(var_types=[gt_class])
return