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# here we are at gene level, must iterate over all variants in this gene
# iterate over variants in this gene
for kkk in GENE_KEY_GT[g]: # this the second key: chr:start:end:ref:alt
CHILD_GT = CHILD_DICT['biallelic_autosomal'][kkk][0]
CHILD_GENE = CHILD_DICT['biallelic_autosomal'][kkk][1]
CHILD_TRANS = CHILD_DICT['biallelic_autosomal'][kkk][2]
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# if a non-normalized INDEL in child G2P - must adjust (should not happen really, we split, normalized and left-aligned the family VCF before sending it to VEP+G2P)
chr,start,end,ref,alt = kkk.split(":")
if len(ref) > 1 and len(alt) > 1: # an INDEL - not normalized
if len(ref) < len(alt): # an INS
orig_start = start
orig_ref = ref
orig_alt = alt
start = orig_start
ref = '-'
alt = orig_alt[len(orig_ref):]
print " WARNING: original INS = %s:%s:%s:%s:%s --> replaced with INS = %s:%s:%s:%s" % (chr,orig_start,end,orig_ref,orig_alt,chr,start,ref,alt)
else: # a DEL
print "ERROR: At the momemnt, cannot deal with this non-normalized deletion"
print line
raise SystemExit
new_key = '%s:%s:%s:%s' % (chr,start,ref,alt)
# record the data for CHILD G2P variants (for OBS=biallelic)
if new_key not in G2P_DICT:
G2P_DICT[new_key] = 0
else:
# print "ERROR: duplicate G2P variant new_key = %s" % (new_key)
# raise SystemExit
# this will happen if a gene is e.g. hemizygous,x-linked dominant - there will be two separate lines in the output for each req
pass
# and record the required data (CHILD_TRANS,CHILD_GENE,CHILD_GT) in G2P_DATA
if new_key not in G2P_DATA:
G2P_DATA[new_key] = (CHILD_TRANS,CHILD_GENE,CHILD_GT)
else:
# print "ERROR: duplicate G2P variant new_key = %s" % (new_key)
# raise SystemExit
# this will happen if a gene is e.g. hemizygous,x-linked dominant - there will be two separate lines in the output for each req
pass
NUM_UNIQ_G2P_VARS = len(G2P_DICT)
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print "Found %s unique G2P variants in CHILD (%s) after considering MONOALLELIC and BIALLELIC genes" % (NUM_UNIQ_G2P_VARS,CHILD_ID)
sys.stdout.flush()
print ""
####################################################################################################################
#### X-linked filtering ####
#.# #### under the x-linked model (OBS == hemizygous or x-linked dominant, but NOT x-linked over-dominance) ####
#### under the chrX model (OBS == monoallelic_X_hem or monoallelic_X_het) ####
#### exclude child HET variants if seen as HOM in UNAFFECTED father ####
#### ####
#### Note 18/01/2022 ####
#### This is a temporary solution, since x-linked dominant and x-linked over-dominance -> monoallelic_X_het ####
#### and we should filter x-linked dominant and monoallelic_X_hem, but not x-linked over-dominance ####
#### the code below treats x-linked over-dominance as the others (i.e. filters, while it should not) ####
#### Issue flagged to G2P plug-in team, awaiting their fix ####
#### for now manually scan the output of G2P for the proband (both for boys and girls) ####
#### to check if any variant has been called in PCDH19 and EFNB1 ####
#### also for all the variants filtered out from monoallelic_X_het we will print in the log the gene name ####
####################################################################################################################
print ""
print "=== X-linked filtering ==="
#######################################
### process monoallelic_X_hem genes ###
#######################################
for key in CHILD_DICT['monoallelic_X_hem']: # this the second key: chr:start:end:ref:alt; value: (ZYG,gene,trans)
CHILD_GT = CHILD_DICT['monoallelic_X_hem'][key][0]
CHILD_GENE = CHILD_DICT['monoallelic_X_hem'][key][1]
CHILD_TRANS = CHILD_DICT['monoallelic_X_hem'][key][2]
if CHILD_GT == 'HOM': # do NOT filter HOM variants in proband (i.e., hemizygous in boy or HOM in girl)
pass
else:
if (key in DAD_DICT['monoallelic_X_hem']) and (DAD_STAT == "UNAFFECTED"):
DAD_GT = DAD_DICT['monoallelic_X_hem'][key][0]
if DAD_GT == 'HOM': # i.e., hemizygous variant in unaffected father
print "***[monoallelic_X_hem]*** Excluded CHILD var %s in gene = %s, CHILD_GT = %s, DAD_GT = %s, DAD_STAT = %s" % (key,CHILD_GENE,CHILD_GT,DAD_GT,DAD_STAT)
continue
# if a non-normalized INDEL in child G2P - must adjust (should not happen really, we split, normalized and left-aligned the family VCF before sending it to VEP+G2P)
chr,start,end,ref,alt = key.split(":")
if len(ref) > 1 and len(alt) > 1: # an INDEL - not normalized
if len(ref) < len(alt): # an INS
orig_start = start
orig_ref = ref
orig_alt = alt
start = orig_start
ref = '-'
alt = orig_alt[len(orig_ref):]
print " WARNING: original INS = %s:%s:%s:%s:%s --> replaced with INS = %s:%s:%s:%s" % (chr,orig_start,end,orig_ref,orig_alt,chr,start,ref,alt)
else: # a DEL
print "ERROR: At the momemnt, cannot deal with this non-normalized deletion"
print line
raise SystemExit
new_key = '%s:%s:%s:%s' % (chr,start,ref,alt)
# record the data for CHILD G2P variants (for OBS=monoallelic_X_hem)
if new_key not in G2P_DICT:
G2P_DICT[new_key] = 0
else:
# print "ERROR: duplicate G2P variant new_key = %s" % (new_key)
# raise SystemExit
# this will happen if a gene is e.g. hemizygous,x-linked dominant - there will be two separate lines in the output for each req
pass
# and record the required data (CHILD_TRANS,CHILD_GENE,CHILD_GT) in G2P_DATA
if new_key not in G2P_DATA:
G2P_DATA[new_key] = (CHILD_TRANS,CHILD_GENE,CHILD_GT)
else:
# print "ERROR: duplicate G2P variant new_key = %s" % (new_key)
# raise SystemExit
# this will happen if a gene is e.g. hemizygous,x-linked dominant - there will be two separate lines in the output for each req
pass
#######################################
### process monoallelic_X_het genes ###
#######################################
for key in CHILD_DICT['monoallelic_X_het']: # this the second key: chr:start:end:ref:alt; value: (ZYG,gene,trans)
CHILD_GT = CHILD_DICT['monoallelic_X_het'][key][0]
CHILD_GENE = CHILD_DICT['monoallelic_X_het'][key][1]
CHILD_TRANS = CHILD_DICT['monoallelic_X_het'][key][2]
if CHILD_GT == 'HOM': # do NOT filter HOM variants (i.e., hemizygous in boy or HOM in girl)
pass
else:
if (key in DAD_DICT['monoallelic_X_het']) and (DAD_STAT == "UNAFFECTED"):
DAD_GT = DAD_DICT['monoallelic_X_het'][key][0]
if DAD_GT == 'HOM': # i.e., x-linked dominant variant in unnafected father
print "***[monoallelic_X_het]*** Excluded CHILD var %s in gene = %s, CHILD_GT = %s, DAD_GT = %s, DAD_STAT = %s" % (key,CHILD_GENE,CHILD_GT,DAD_GT,DAD_STAT)
continue
# if a non-normalized INDEL in child G2P - must adjust (should not happen really, we split, normalized and left-aligned the family VCF before sending it to VEP+G2P)
chr,start,end,ref,alt = key.split(":")
if len(ref) > 1 and len(alt) > 1: # an INDEL - not normalized
if len(ref) < len(alt): # an INS
orig_start = start
orig_ref = ref
orig_alt = alt
start = orig_start
ref = '-'
alt = orig_alt[len(orig_ref):]
print " WARNING: original INS = %s:%s:%s:%s:%s --> replaced with INS = %s:%s:%s:%s" % (chr,orig_start,end,orig_ref,orig_alt,chr,start,ref,alt)
else: # a DEL
print "ERROR: At the momemnt, cannot deal with this non-normalized deletion"
print line
raise SystemExit
new_key = '%s:%s:%s:%s' % (chr,start,ref,alt)
# record the data for CHILD G2P variants (for OBS=monoallelic_X_het)
if new_key not in G2P_DICT:
G2P_DICT[new_key] = 0
else:
# print "ERROR: duplicate G2P variant new_key = %s" % (new_key)
# raise SystemExit
# this will happen if a gene is e.g. hemizygous,x-linked dominant - there will be two separate lines in the output for each req
pass
# and record the required data (CHILD_TRANS,CHILD_GENE,CHILD_GT) in G2P_DATA
if new_key not in G2P_DATA:
G2P_DATA[new_key] = (CHILD_TRANS,CHILD_GENE,CHILD_GT)
else:
# print "ERROR: duplicate G2P variant new_key = %s" % (new_key)
# raise SystemExit
# this will happen if a gene is e.g. hemizygous,x-linked dominant - there will be two separate lines in the output for each req
pass
NUM_UNIQ_G2P_VARS = len(G2P_DICT)
print "Found %s unique G2P variants in CHILD (%s) after considering MONOALLELIC, BIALLELIC and X-LINKED genes" % (NUM_UNIQ_G2P_VARS,CHILD_ID)
sys.stdout.flush()
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print ""
print ""
def read_ped(in_file):
global CHILD_ID
global CHILD_SEX
global DEC_CHILD_SEX
global MOM_ID
global MOM_STAT
global DAD_ID
global DAD_STAT
CHILD_ID = 0
CHILD_SEX = 0
MOM_ID = 0
MOM_STAT = 0
DAD_ID = 0
DAD_STAT = 0
in_han = open(in_file,'r')
for line in in_han:
data = [x.strip() for x in line.strip().split('\t')]
if data[2] != '0' and data[3] != '0': # this is the child in the trio
if CHILD_ID == 0:
CHILD_ID = data[1]
else: # seen another child
print "ERROR: already have seen a child (possibly a quad) - cannot handle at the moment"
raise SystemExit
if DAD_ID == 0:
DAD_ID = data[2]
else:
if data[2] != DAD_ID:
print "ERROR: DAD_ID mismatch - from child line dad_id = %s, from dad line dad_id = %s" % (data[2],DAD_ID)
raise SystemExit
if MOM_ID == 0:
MOM_ID = data[3]
else:
if data[3] != MOM_ID:
print "ERROR: MOM_ID mismatch - from child line mom_id = %s, from mom line mom_id = %s" % (data[3],MOM_ID)
raise SystemExit
CHILD_SEX = int(data[4])
if CHILD_SEX == 1: # boy
DEC_CHILD_SEX = '46XY'
elif CHILD_SEX == 2: # girl
DEC_CHILD_SEX = '46XX'
else:
print "ERROR: proband sex unknown"
print line
raise SystemExit
if int(data[5]) != 2:
print "ERROR: child not affected"
print line
raise SystemExit
elif int(data[2]) == 0 and int(data[3]) == 0: # this is a parent record
if int(data[4]) == 1: # this is the dad
if int(data[5]) == 1:
DAD_STAT = "UNAFFECTED"
elif int(data[5]) == 2:
DAD_STAT = "AFFECTED"
else:
print "ERROR: cannot establish the dad's status"
print line
raise SystemExit
if DAD_ID == 0:
DAD_ID = data[1]
else:
if data[1] != DAD_ID:
print "ERROR: DAD_ID mismatch - from dad line dad_id = %s, from child line dad_id = %s" % (data[1],DAD_ID)
raise SystemExit
if int(data[4]) == 2: # this is the mom
if int(data[5]) == 1:
MOM_STAT = "UNAFFECTED"
elif int(data[5]) == 2:
MOM_STAT = "AFFECTED"
else:
print "ERROR: cannot establish mom's status"
print line
raise SystemExit
if MOM_ID == 0:
MOM_ID = data[1]
else:
if data[1] != MOM_ID:
print "ERROR: MOM_ID mismatch - from mom line mom_id = %s, from child line mom_id = %s" % (data[1],MOM_ID)
raise SystemExit
else:
print "ERROR: problematic PED line"
print line
raise SystemExit
def read_map_file(in_file):
in_han = open(in_file,'r')
for line in in_han:
data = [x.strip() for x in line.strip().split('\t')]
dec_id = data[0]
int_id = data[1]
if dec_id not in MAP_DICT:
MAP_DICT[dec_id] = int_id
else:
print "ERROR: duplicate DECIPHER/family ID = %s" % (dec_id)
raise SystemExit
in_han.close()
def read_trans_map(in_file):
in_han = open(in_file,'r')
for line in in_han:
data = [x.strip() for x in line.strip().split('\t')]
old_trans_id = data[0]
new_trans_id = data[1]
if old_trans_id not in TRANS_DICT:
TRANS_DICT[old_trans_id] = new_trans_id
else:
print "ERROR: duplicate old transcript ID = %s" % (old_trans_id)
raise SystemExit
in_han.close()
if __name__ == '__main__':
if len(sys.argv) == 12:
go(sys.argv[1],sys.argv[2],sys.argv[3],sys.argv[4],sys.argv[5],sys.argv[6],sys.argv[7],sys.argv[8],sys.argv[9],sys.argv[10],sys.argv[11])
else:
print "Suggested use: time python /home/u035/u035/shared/scripts/NHS_WES_generate_DEC_IGV.py \
dec_map_file,trans_map_file,ped_file,in_g2p_file,in_vase_file,fam_igv_dir,vcf_dir,plate_id,fam_id,dec_dir,fam_bam_dir"
raise SystemExit