print "Checking sample consistency and creating observation array..."
for line in fin.readlines():
counter += 1
linelist = line.split("\t")
chrom = linelist[headlist.index("CHROM")]
posit = linelist[headlist.index("POS")]
info = linelist[headlist.index("INFO")]
#format = linelist[headlist.index("FORMAT")]
mq, mq0 = vcfUtils.parse_info(info)
if ("#" in line) == 0 and mq >= mapQual and mq0 <= mapQual0 and (
"PASS" in line):
#stat_locations = vcfUtils.stat_grabber(linelist
geno_father = vcfUtils.allele_coder(linelist[father], depth,
altDepth, gtQual, pl,
platform)
geno_mother = vcfUtils.allele_coder(linelist[mother], depth,
altDepth, gtQual, pl,
platform)
geno_offspring = vcfUtils.allele_coder(linelist[offspring],
depth, altDepth, gtQual,
pl, platform)
alleles2 = geno_father + "," + geno_mother + "," + geno_offspring
if ((("3" in alleles2) == 0) and (("4" in alleles2) == 0)):
counter += 1
#checks for paternity, maternity
if geno_father == "0" and geno_mother == "2":
inform_parents += 1
non_maternal = 0
print "Checking sample consistency and creating observation array..."
for line in fin.readlines():
counter+=1
linelist = line.split("\t")
chrom = linelist[headlist.index("CHROM")]
posit = linelist[headlist.index("POS")]
info = linelist[headlist.index("INFO")]
#format = linelist[headlist.index("FORMAT")]
mq, mq0 = vcfUtils.parse_info(info)
if ("#" in line) == 0 and mq >= mapQual and mq0 <= mapQual0 and ("PASS" in line):
#stat_locations = vcfUtils.stat_grabber(linelist
geno_father = vcfUtils.allele_coder(linelist[father], depth, altDepth, gtQual, pl, platform)
geno_mother = vcfUtils.allele_coder(linelist[mother], depth, altDepth, gtQual, pl, platform)
geno_offspring = vcfUtils.allele_coder(linelist[offspring], depth, altDepth, gtQual, pl, platform)
alleles2 = geno_father+","+geno_mother+","+geno_offspring
if ((("3" in alleles2) == 0) and (("4" in alleles2) == 0)):
counter+=1
#checks for paternity, maternity
if geno_father == "0" and geno_mother == "2":
inform_parents += 1
if geno_offspring == "2":
non_paternal += 1
if geno_offspring == "0":
non_maternal += 1
def phase_quartet(fatherID, motherID, offspring1ID, offspring2ID, vcf_in_stem, depth, altDepth, gtQual, mapQual, mapQual0, pl, mat_path, error, compression, mie, selfprob, platform):
nonselfprob = str((1-float(selfprob))/float(5))
#create matrices for HMM, all probabilities in log10 space to avoid underflow from floating point
transmat, emitmat, startp, states, inmap = hmmUtils.make_hmm(mat_path, selfprob, compression, mie, error, "q")
#temp file for inheritance state
phase_out = open(".".join([vcf_in_stem, fatherID, motherID, offspring1ID, offspring2ID, "phase_out.txt"]), "w")
#chrom_arr = ["21", "22"]
chrom_arr = ["1","2","3","4","5","6","7","8","9","10","11","12","13","14","15","16","17","18","19","20","21","22","X"]
start_time=time.clock()
for chromh in chrom_arr:
print "\nWorking on chromosome "+str(chromh)+"\n"
fin = open(vcf_in_stem+"_chr"+chromh+".txt", "r")
header = fin.readline()
#grab proper columns from header for variants
headlist = header.replace("\n", "").split("\t")
try:
offspring1 = headlist.index(offspring1ID)
offspring2 = headlist.index(offspring2ID)
father = headlist.index(fatherID)
mother = headlist.index(motherID)
except ValueError:
return "Error in pedigreeUtils.phase_quartet: Invalid input for quartet "+":".join([fatherID, motherID, offspring1ID, offspring2ID])+" - Specified subject ID does not match vcf file header, consider malformed header or pedigree file"
#arrays for observations and positions
obs_seq = []
position_clean = []
position_all = []
res_dict = {}
#counters for error modes (DN = de novo allele, HZGC = apparent gene conversions/hemizygosity
counterDN1 = 0
counterHZGC1 = 0
counterDN2 = 0
counterHZGC2 = 0
counter = 0
#counters for number of informative allele assortments for determing paternity/maternity
inform_parents = 0
non_paternal1 = 0
non_maternal1 = 0
non_paternal2 = 0
non_maternal2 = 0
for line in fin.readlines():
if ("#" in line) == 0:
linelist = line.replace("\n", "").split("\t")
chrom = linelist[headlist.index("CHROM")]
posit = linelist[headlist.index("POS")]
info = linelist[headlist.index("INFO")]
position_all.append(posit)
#temp variable to flag if line should be used, and also check for unsupported data format (currently supports CG and Illumina GATK-style)
goline = 0
if ((platform == "ILLUMINA") or (platform == "ILL")):
try:
mq, mq0 = vcfUtils.parse_info(info)
if mq >= mapQual and mq0 <= mapQual0 and ("PASS" in line):
goline = 1
except UnboundLocalError:
return "Error in pedigreeUtils.phase_quartet for quartet "+":".join([fatherID, motherID, offspring1ID, offspring2ID])+" - Invalid input format: Data does not appear to be in GATK style from Illumina platform"
elif (platform == "COMPLETE") or (platform == "CG"):
goline = 1
elif (platform == "RTG") or (platform == "rtg"):
goline = 1
elif (platform != "COMPLETE") and (platform != "CG") and (platform != "ILLUMINA") and (platform != "ILL"):
return "Error in pedigreeUtils.phase_quartet for quartet "+":".join([fatherID, motherID, offspring1ID, offspring2ID])+": Invalid input - unknown or unsupported data format: "+platform
if goline == 1:
geno_father = vcfUtils.allele_coder(linelist[father], depth, altDepth, gtQual, pl, platform)
geno_mother = vcfUtils.allele_coder(linelist[mother], depth, altDepth, gtQual, pl, platform)
geno_offspring1 = vcfUtils.allele_coder(linelist[offspring1], depth, altDepth, gtQual, pl, platform)
geno_offspring2 = vcfUtils.allele_coder(linelist[offspring2], depth, altDepth, gtQual, pl, platform)
alleles2 = geno_father+","+geno_mother+","+geno_offspring1+","+geno_offspring2
if ((("3" in alleles2) == 0) and (("4" in alleles2) == 0)):
counter+=1
#checks for paternity, maternity
if geno_father == "0" and geno_mother == "2":
inform_parents += 1
if geno_offspring1 == "2":
non_paternal1 += 1
if geno_offspring1 == "0":
non_maternal1 += 1
if geno_offspring2 == "2":
non_paternal2 += 1
if geno_offspring2 == "0":
non_maternal2 += 1
elif geno_father == "2" and geno_mother == "0":
inform_parents += 1
if geno_offspring1 == "0":
non_paternal1 += 1
if geno_offspring1 == "2":
non_maternal1 += 1
if geno_offspring2 == "0":
non_paternal2 += 1
if geno_offspring2 == "2":
non_maternal2 += 1
#simple de novo case
if alleles2 == "0,0,1,1":
counterDN1+=1
counterDN2+=1
elif alleles2 == "0,0,1,0":
counterDN1+=1
elif alleles2 == "0,0,0,1":
counterDN2+=1
#hemizygosity or gene conversion case
elif (geno_father == "0" and geno_mother == "0" and geno_offspring1 == "2") or (geno_father == "1" and geno_mother == "0" and geno_offspring1 == "2") or (geno_father == "0" and geno_mother == "1" and geno_offspring1 == "2") or (geno_father == "1" and geno_mother == "2" and geno_offspring1 == "0") or (geno_father == "2" and geno_mother == "1" and geno_offspring1 == "0"):
counterHZGC1+=1
elif (geno_father == "0" and geno_mother == "0" and geno_offspring2 == "2") or (geno_father == "1" and geno_mother == "0" and geno_offspring2 == "2") or (geno_father == "0" and geno_mother == "1" and geno_offspring2 == "2") or (geno_father == "1" and geno_mother == "2" and geno_offspring2 == "0") or (geno_father == "2" and geno_mother == "1" and geno_offspring2 == "0"):
counterHZGC2+=1
#creates an array of clean observations for HMM
if inmap.has_key(alleles2):
obs_seq.append(int(inmap[alleles2]))
position_clean.append(posit)
fin.close()
cent_np1 = float(non_paternal1)/float(inform_parents)
cent_nm1 = float(non_maternal1)/float(inform_parents)
cent_DN1 = float(counterDN1+counterHZGC1)/float(counter)
cent_np2 = float(non_paternal2)/float(inform_parents)
cent_nm2 = float(non_maternal2)/float(inform_parents)
cent_DN2 = float(counterDN2+counterHZGC2)/float(counter)
print "\nAllele QC summary for quartet: "+str(":".join([fatherID, motherID, offspring1ID, offspring2ID])+"\n")
print "\nNon-transmitted paternal alleles for child 1 (%): "+str(cent_np1*float(100))
print "Non-transmitted maternal alleles for child 1 (%): "+str(cent_nm1*float(100))
print "Novel alleles for child 1 (%): "+str(cent_DN1*float(100))
print "\nNon-transmitted paternal alleles for child 2 (%): "+str(cent_np2*float(100))
print "Non-transmitted maternal alleles for child 2 (%): "+str(cent_nm2*float(100))
print "Novel alleles for child 2 (%): "+str(cent_DN2*float(100))
#warning for high rates of non-transmission, does not kill process
if (cent_np1) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of non-transmission of paternal alleles in child "+offspring1ID+": consider sample mix-up or non-paternity...\n"
if (cent_np2) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of non-transmission of paternal alleles in child "+offspring2ID+": consider sample mix-up or non-paternity...\n"
if (cent_nm1) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of non-transmission of maternal alleles in child "+offspring1ID+": consider sample mix-up or non-maternity...\n"
if (cent_nm2) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of non-transmission of maternal alleles in child "+offspring2ID+": consider sample mix-up or non-maternity...\n"
if (cent_DN1) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of novel alleles in child "+offspring1ID+": consider sample mix-up or non-maternity or non-paternity...\n"
if (cent_DN2) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of novel alleles in child "+offspring2ID+": consider sample mix-up or non-maternity or non-paternity...\n"
#run Viterbi algorithm on HMM defined above
vit = hmmUtils.viterbi(np.array(obs_seq), states, startp, transmat, emitmat)
vit_path = vit[1]
#bind viterbi path to position dict for annotation
for i in range(0, len(vit_path)):
res_dict[position_clean[i]] = vit_path[i]
#temp variables to allow bridging alleles not used in HMM
firstpath = lastpath = vit_path[0]
#create output dict with state for every position, including those not used in HMM
for i in position_all:
if res_dict.has_key(i):
phase_out.write("chr"+chromh+":"+str(i)+"\t"+str(res_dict[i])+"\n")
lastpath = res_dict[i]
else:
phase_out.write("chr"+chromh+":"+str(i)+"\t"+str(lastpath)+"\n")
end_time = time.clock()
phase_out.close()
return "Normal exit status for quartet "+":".join([fatherID, motherID, offspring1ID, offspring2ID])+". Processing time: "+str((float(end_time)-float(start_time))/float(60))+" minutes"
def phase_quartet(fatherID, motherID, offspring1ID, offspring2ID, vcf_in_stem,
depth, altDepth, gtQual, mapQual, mapQual0, pl, mat_path,
error, compression, mie, selfprob, platform):
nonselfprob = str((1 - float(selfprob)) / float(5))
#create matrices for HMM, all probabilities in log10 space to avoid underflow from floating point
transmat, emitmat, startp, states, inmap = hmmUtils.make_hmm(
mat_path, selfprob, compression, mie, error, "q")
#temp file for inheritance state
phase_out = open(
".".join([
vcf_in_stem, fatherID, motherID, offspring1ID, offspring2ID,
"phase_out.txt"
]), "w")
#chrom_arr = ["21", "22"]
chrom_arr = [
"1", "2", "3", "4", "5", "6", "7", "8", "9", "10", "11", "12", "13",
"14", "15", "16", "17", "18", "19", "20", "21", "22", "X"
]
start_time = time.clock()
for chromh in chrom_arr:
print "\nWorking on chromosome " + str(chromh) + "\n"
fin = open(vcf_in_stem + "_chr" + chromh + ".txt", "r")
header = fin.readline()
#grab proper columns from header for variants
headlist = header.replace("\n", "").split("\t")
try:
offspring1 = headlist.index(offspring1ID)
offspring2 = headlist.index(offspring2ID)
father = headlist.index(fatherID)
mother = headlist.index(motherID)
except ValueError:
return "Error in pedigreeUtils.phase_quartet: Invalid input for quartet " + ":".join(
[fatherID, motherID, offspring1ID, offspring2ID]
) + " - Specified subject ID does not match vcf file header, consider malformed header or pedigree file"
#arrays for observations and positions
obs_seq = []
position_clean = []
position_all = []
res_dict = {}
#counters for error modes (DN = de novo allele, HZGC = apparent gene conversions/hemizygosity
counterDN1 = 0
counterHZGC1 = 0
counterDN2 = 0
counterHZGC2 = 0
counter = 0
#counters for number of informative allele assortments for determing paternity/maternity
inform_parents = 0
non_paternal1 = 0
non_maternal1 = 0
non_paternal2 = 0
non_maternal2 = 0
for line in fin.readlines():
if ("#" in line) == 0:
linelist = line.replace("\n", "").split("\t")
chrom = linelist[headlist.index("CHROM")]
posit = linelist[headlist.index("POS")]
info = linelist[headlist.index("INFO")]
position_all.append(posit)
#temp variable to flag if line should be used, and also check for unsupported data format (currently supports CG and Illumina GATK-style)
goline = 0
if ((platform == "ILLUMINA") or (platform == "ILL")):
try:
mq, mq0 = vcfUtils.parse_info(info)
if mq >= mapQual and mq0 <= mapQual0 and ("PASS"
in line):
goline = 1
except UnboundLocalError:
return "Error in pedigreeUtils.phase_quartet for quartet " + ":".join(
[fatherID, motherID, offspring1ID, offspring2ID]
) + " - Invalid input format: Data does not appear to be in GATK style from Illumina platform"
elif (platform == "COMPLETE") or (platform == "CG"):
goline = 1
elif (platform == "RTG") or (platform == "rtg"):
goline = 1
elif (platform != "COMPLETE") and (platform != "CG") and (
platform != "ILLUMINA") and (platform != "ILL"):
return "Error in pedigreeUtils.phase_quartet for quartet " + ":".join(
[fatherID, motherID, offspring1ID, offspring2ID]
) + ": Invalid input - unknown or unsupported data format: " + platform
if goline == 1:
geno_father = vcfUtils.allele_coder(
linelist[father], depth, altDepth, gtQual, pl,
platform)
geno_mother = vcfUtils.allele_coder(
linelist[mother], depth, altDepth, gtQual, pl,
platform)
geno_offspring1 = vcfUtils.allele_coder(
linelist[offspring1], depth, altDepth, gtQual, pl,
platform)
geno_offspring2 = vcfUtils.allele_coder(
linelist[offspring2], depth, altDepth, gtQual, pl,
platform)
alleles2 = geno_father + "," + geno_mother + "," + geno_offspring1 + "," + geno_offspring2
if ((("3" in alleles2) == 0) and (("4" in alleles2) == 0)):
counter += 1
#checks for paternity, maternity
if geno_father == "0" and geno_mother == "2":
inform_parents += 1
if geno_offspring1 == "2":
non_paternal1 += 1
if geno_offspring1 == "0":
non_maternal1 += 1
if geno_offspring2 == "2":
non_paternal2 += 1
if geno_offspring2 == "0":
non_maternal2 += 1
elif geno_father == "2" and geno_mother == "0":
inform_parents += 1
if geno_offspring1 == "0":
non_paternal1 += 1
if geno_offspring1 == "2":
non_maternal1 += 1
if geno_offspring2 == "0":
non_paternal2 += 1
if geno_offspring2 == "2":
non_maternal2 += 1
#simple de novo case
if alleles2 == "0,0,1,1":
counterDN1 += 1
counterDN2 += 1
elif alleles2 == "0,0,1,0":
counterDN1 += 1
elif alleles2 == "0,0,0,1":
counterDN2 += 1
#hemizygosity or gene conversion case
elif (geno_father == "0" and geno_mother == "0"
and geno_offspring1 == "2") or (
geno_father == "1" and geno_mother == "0"
and geno_offspring1 == "2") or (
geno_father == "0" and geno_mother == "1"
and geno_offspring1 == "2") or (
geno_father == "1"
and geno_mother == "2"
and geno_offspring1 == "0") or (
geno_father == "2"
and geno_mother == "1"
and geno_offspring1 == "0"):
counterHZGC1 += 1
elif (geno_father == "0" and geno_mother == "0"
and geno_offspring2 == "2") or (
geno_father == "1" and geno_mother == "0"
and geno_offspring2 == "2") or (
geno_father == "0" and geno_mother == "1"
and geno_offspring2 == "2") or (
geno_father == "1"
and geno_mother == "2"
and geno_offspring2 == "0") or (
geno_father == "2"
and geno_mother == "1"
and geno_offspring2 == "0"):
counterHZGC2 += 1
#creates an array of clean observations for HMM
if inmap.has_key(alleles2):
obs_seq.append(int(inmap[alleles2]))
position_clean.append(posit)
fin.close()
cent_np1 = float(non_paternal1) / float(inform_parents)
cent_nm1 = float(non_maternal1) / float(inform_parents)
cent_DN1 = float(counterDN1 + counterHZGC1) / float(counter)
cent_np2 = float(non_paternal2) / float(inform_parents)
cent_nm2 = float(non_maternal2) / float(inform_parents)
cent_DN2 = float(counterDN2 + counterHZGC2) / float(counter)
print "\nAllele QC summary for quartet: " + str(
":".join([fatherID, motherID, offspring1ID, offspring2ID]) + "\n")
print "\nNon-transmitted paternal alleles for child 1 (%): " + str(
cent_np1 * float(100))
print "Non-transmitted maternal alleles for child 1 (%): " + str(
cent_nm1 * float(100))
print "Novel alleles for child 1 (%): " + str(cent_DN1 * float(100))
print "\nNon-transmitted paternal alleles for child 2 (%): " + str(
cent_np2 * float(100))
print "Non-transmitted maternal alleles for child 2 (%): " + str(
cent_nm2 * float(100))
print "Novel alleles for child 2 (%): " + str(cent_DN2 * float(100))
#warning for high rates of non-transmission, does not kill process
if (cent_np1) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of non-transmission of paternal alleles in child " + offspring1ID + ": consider sample mix-up or non-paternity...\n"
if (cent_np2) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of non-transmission of paternal alleles in child " + offspring2ID + ": consider sample mix-up or non-paternity...\n"
if (cent_nm1) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of non-transmission of maternal alleles in child " + offspring1ID + ": consider sample mix-up or non-maternity...\n"
if (cent_nm2) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of non-transmission of maternal alleles in child " + offspring2ID + ": consider sample mix-up or non-maternity...\n"
if (cent_DN1) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of novel alleles in child " + offspring1ID + ": consider sample mix-up or non-maternity or non-paternity...\n"
if (cent_DN2) > 0.05 and (chromh != 'X'):
print "\nWARNING! High rate of novel alleles in child " + offspring2ID + ": consider sample mix-up or non-maternity or non-paternity...\n"
#run Viterbi algorithm on HMM defined above
vit = hmmUtils.viterbi(np.array(obs_seq), states, startp, transmat,
emitmat)
vit_path = vit[1]
#bind viterbi path to position dict for annotation
for i in range(0, len(vit_path)):
res_dict[position_clean[i]] = vit_path[i]
#temp variables to allow bridging alleles not used in HMM
firstpath = lastpath = vit_path[0]
#create output dict with state for every position, including those not used in HMM
for i in position_all:
if res_dict.has_key(i):
phase_out.write("chr" + chromh + ":" + str(i) + "\t" +
str(res_dict[i]) + "\n")
lastpath = res_dict[i]
else:
phase_out.write("chr" + chromh + ":" + str(i) + "\t" +
str(lastpath) + "\n")
end_time = time.clock()
phase_out.close()
return "Normal exit status for quartet " + ":".join([
fatherID, motherID, offspring1ID, offspring2ID
]) + ". Processing time: " + str(
(float(end_time) - float(start_time)) / float(60)) + " minutes"