def get_header(vcf_file_path):
"""Parse the header and return a header object
Args:
vcf_file_path(str): Path to vcf
Returns:
head: A HeaderParser object
"""
logger.info("Parsing header of file {0}".format(vcf_file_path))
head = HeaderParser()
handle = get_vcf_handle(infile=vcf_file_path)
# Parse the header
for line in handle:
line = line.rstrip()
if line.startswith('#'):
if line.startswith('##'):
head.parse_meta_data(line)
else:
head.parse_header_line(line)
else:
break
handle.close()
return head
def cli(ctx, variant_file, family_file, family_type, gq_treshold, to_json,
outfile, verbose):
"""Check for pedigree inconsistensies."""
# configure root logger to print to STDERR
loglevel = LEVELS.get(min(verbose, 3))
configure_stream(level=loglevel)
if not family_file:
logger.error("Please provide a family file with -f/--family_file")
logger.info("Exiting")
sys.exit(1)
logger.info("Setting up a family parser")
family_parser = FamilyParser(family_file, family_type)
logger.debug("Family parser done")
# The individuals in the ped file must be present in the variant file:
families = family_parser.families
logger.info("Families used in analysis: {0}".format(
','.join(list(families.keys()))))
ctx.gq_treshold = gq_treshold
ctx.to_json = to_json
ctx.outfile = outfile
ctx.families = families
ctx.individuals = family_parser.individuals
head = HeaderParser()
for line in variant_file:
line = line.rstrip()
if line.startswith('#'):
if line.startswith('##'):
head.parse_meta_data(line)
else:
head.parse_header_line(line)
else:
break
#Add the first variant to the iterator
if line:
variant_file = itertools.chain([line], variant_file)
try:
check_individuals(family_parser.individuals, head.individuals)
except IOError as e:
logger.error(e)
logger.info("Individuals in PED file: {0}".format(
', '.join(family_parser.individuals)))
logger.info("Individuals in VCF file: {0}".format(', '.join(vcf_individuals)))
logger.info("Exiting...")
ctx.abort()
ctx.variant_file = variant_file
ctx.header_line = head.header
def get_header(vcf_lines):
"""Parse the vcf lines and return a header object"""
head = HeaderParser()
for line in vcf_lines:
if line.startswith('#'):
if line.startswith('##'):
head.parse_meta_data(line)
else:
head.parse_header_line(line)
return head
def test_vep_columns():
"""
Test how the vep columns are parsed
"""
header_parser = HeaderParser()
vep_info_line = '##INFO=<ID=CSQ,Number=.,Type=String,Description="Consequence'\
' type as predicted by VEP. Format: Allele|Gene|Feature|Feature_type|Consequence">'
header_parser.parse_meta_data(vep_info_line)
assert header_parser.vep_columns == ['Allele','Gene','Feature','Feature_type','Consequence']
def test_vep_columns():
"""
Test how the vep columns are parsed
"""
header_parser = HeaderParser()
vep_info_line = '##INFO=<ID=CSQ,Number=.,Type=String,Description="Consequence'\
' type as predicted by VEP. Format: Allele|Gene|Feature|Feature_type|Consequence">'
header_parser.parse_meta_data(vep_info_line)
assert header_parser.vep_columns == [
'Allele', 'Gene', 'Feature', 'Feature_type', 'Consequence'
]
def test_parse_vcf_lines():
"""
Test how the header parser behaves with simple vcf lines
"""
header_parser = HeaderParser()
header_lines = [
'##fileformat=VCFv4.2',
'##FILTER=<ID=LowQual,Description="Low quality">',
'##INFO=<ID=MQ,Number=1,Type=Float,Description="RMS Mapping Quality">',
'##INFO=<ID=CNT,Number=A,Type=Integer,Description="Number of times '\
'this allele was found in external db">',
'##contig=<ID=1,length=249250621,assembly=b37>',
'##INFO=<ID=DP_HIST,Number=R,Type=String,Description="Histogram for '\
'DP; Mids: 2.5|7.5|12.5|17.5|22.5|27.5|32.5|37.5|42.5|47.5|52.5|57.5|'\
'62.5|67.5|72.5|77.5|82.5|87.5|92.5|97.5">',
'##FORMAT=<ID=AD,Number=.,Type=Integer,Description="Allelic depths for'\
' the ref and alt alleles in the order listed">',
'##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth">',
'##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">',
'##FORMAT=<ID=GQ,Number=1,Type=String,Description="GenotypeQuality">'
'##reference=file:///human_g1k_v37.fasta',
'#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT\tfather\tmother\tproband'
]
for line in header_lines:
if line.startswith('##'):
header_parser.parse_meta_data(line)
elif line.startswith('#'):
header_parser.parse_header_line(line)
assert header_parser.fileformat == "VCFv4.2"
assert header_parser.individuals == ['father','mother','proband']
assert header_parser.vep_columns == []
assert "MQ" in header_parser.extra_info
assert header_parser.extra_info["MQ"]['Description'] == "RMS Mapping Quality"
assert header_parser.extra_info["CNT"]['Number'] == "A"
assert header_parser.extra_info["CNT"]['Type'] == "Integer"
assert "CNT" in header_parser.extra_info
assert "DP_HIST" in header_parser.extra_info
assert "LowQual" in header_parser.filter_dict
assert "1" in header_parser.contig_dict
assert header_parser.header == [
'CHROM','POS','ID','REF','ALT','QUAL','FILTER','INFO','FORMAT',
'father','mother','proband'
]
def get_header(vcf_file_path):
"""Parse the header and return a header object
Args:
vcf_file_path(str): Path to vcf
Returns:
head: A HeaderParser object
"""
logger.info("Parsing header of file {0}".format(vcf_file_path))
head = HeaderParser()
handle = get_vcf_handle(infile=vcf_file_path)
# Parse the header
for line in handle:
line = line.rstrip()
if line.startswith('#'):
if line.startswith('##'):
head.parse_meta_data(line)
else:
head.parse_header_line(line)
else:
break
handle.close()
return head
def get_header(vcf_lines):
"""Parse the vcf lines and return a header object"""
head = HeaderParser()
for line in vcf_lines:
if line.startswith('#'):
if line.startswith('##'):
head.parse_meta_data(line)
else:
head.parse_header_line(line)
return head
def test_malformed_lines():
"""
Test how the header parser behaves with simple vcf lines
"""
header_parser = HeaderParser()
malformed_fileformat = '##fileformat'
malformed_info_line = '##INFO=<ID=MQ,Number=1,Description="RMS Mapping Quality">'
malformed_contig_line = '##contig=<assembly=b37>'
with pytest.raises(SyntaxError):
header_parser.parse_meta_data(malformed_fileformat)
with pytest.raises(SyntaxError):
header_parser.parse_meta_data(malformed_info_line)
with pytest.raises(SyntaxError):
header_parser.parse_meta_data(malformed_contig_line)
def test_parse_vcf_lines():
"""
Test how the header parser behaves with simple vcf lines
"""
header_parser = HeaderParser()
header_lines = [
'##fileformat=VCFv4.2',
'##FILTER=<ID=LowQual,Description="Low quality">',
'##INFO=<ID=MQ,Number=1,Type=Float,Description="RMS Mapping Quality">',
'##INFO=<ID=CNT,Number=A,Type=Integer,Description="Number of times '\
'this allele was found in external db">',
'##contig=<ID=1,length=249250621,assembly=b37>',
'##INFO=<ID=DP_HIST,Number=R,Type=String,Description="Histogram for '\
'DP; Mids: 2.5|7.5|12.5|17.5|22.5|27.5|32.5|37.5|42.5|47.5|52.5|57.5|'\
'62.5|67.5|72.5|77.5|82.5|87.5|92.5|97.5">',
'##FORMAT=<ID=AD,Number=.,Type=Integer,Description="Allelic depths for'\
' the ref and alt alleles in the order listed">',
'##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Read Depth">',
'##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">',
'##FORMAT=<ID=GQ,Number=1,Type=String,Description="GenotypeQuality">'
'##reference=file:///human_g1k_v37.fasta',
'#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT\tfather\tmother\tproband'
]
for line in header_lines:
if line.startswith('##'):
header_parser.parse_meta_data(line)
elif line.startswith('#'):
header_parser.parse_header_line(line)
assert header_parser.fileformat == "VCFv4.2"
assert header_parser.individuals == ['father', 'mother', 'proband']
assert header_parser.vep_columns == []
assert "MQ" in header_parser.extra_info
assert header_parser.extra_info["MQ"][
'Description'] == "RMS Mapping Quality"
assert header_parser.extra_info["CNT"]['Number'] == "A"
assert header_parser.extra_info["CNT"]['Type'] == "Integer"
assert "CNT" in header_parser.extra_info
assert "DP_HIST" in header_parser.extra_info
assert "LowQual" in header_parser.filter_dict
assert "1" in header_parser.contig_dict
assert header_parser.header == [
'CHROM', 'POS', 'ID', 'REF', 'ALT', 'QUAL', 'FILTER', 'INFO', 'FORMAT',
'father', 'mother', 'proband'
]
def test_malformed_lines():
"""
Test how the header parser behaves with simple vcf lines
"""
header_parser = HeaderParser()
malformed_fileformat = '##fileformat'
malformed_info_line = '##INFO=<ID=MQ,Number=1,Description="RMS Mapping Quality">'
malformed_contig_line = '##contig=<assembly=b37>'
with pytest.raises(SyntaxError):
header_parser.parse_meta_data(malformed_fileformat)
with pytest.raises(SyntaxError):
header_parser.parse_meta_data(malformed_info_line)
with pytest.raises(SyntaxError):
header_parser.parse_meta_data(malformed_contig_line)
def _formated_variants(self, raw_variants, case_obj):
"""Return variant objects
Args:
raw_variants (Iterable): An iterable with variant lines
case_obj (puzzle.nodels.Case): A case object
"""
vcf_file_path = case_obj.variant_source
logger.info("Parsing file {0}".format(vcf_file_path))
head = HeaderParser()
handle = get_vcf_handle(infile=vcf_file_path)
# Parse the header
for line in handle:
line = line.rstrip()
if line.startswith("#"):
if line.startswith("##"):
head.parse_meta_data(line)
else:
head.parse_header_line(line)
else:
break
handle.close()
header_line = head.header
# Get the individual ids for individuals in vcf file
vcf_individuals = set([ind_id for ind_id in head.individuals])
variant_columns = ["CHROM", "POS", "ID", "REF", "ALT", "QUAL", "FILTER"]
vep_header = head.vep_columns
snpeff_header = head.snpeff_columns
index = 0
for variant_line in raw_variants:
if not variant_line.startswith("#"):
index += 1
# Create a variant dict:
variant_dict = get_variant_dict(variant_line=variant_line, header_line=header_line)
variant_dict["CHROM"] = variant_dict["CHROM"].lstrip("chrCHR")
# Crreate a info dict:
info_dict = get_info_dict(info_line=variant_dict["INFO"])
# Check if vep annotation:
vep_string = info_dict.get("CSQ")
# Check if snpeff annotation:
snpeff_string = info_dict.get("ANN")
if vep_string:
# Get the vep annotations
vep_info = get_vep_info(vep_string=vep_string, vep_header=vep_header)
elif snpeff_string:
# Get the vep annotations
snpeff_info = get_snpeff_info(snpeff_string=snpeff_string, snpeff_header=snpeff_header)
variant = Variant(**{column: variant_dict.get(column, ".") for column in variant_columns})
logger.debug("Creating a variant object of variant {0}".format(variant.get("variant_id")))
variant["index"] = index
logger.debug("Updating index to: {0}".format(index))
variant["start"] = int(variant_dict["POS"])
if self.variant_type == "sv":
other_chrom = variant["CHROM"]
# If we have a translocation:
if ":" in variant_dict["ALT"] and not "<" in variant_dict["ALT"]:
other_coordinates = variant_dict["ALT"].strip("ACGTN[]").split(":")
other_chrom = other_coordinates[0].lstrip("chrCHR")
other_position = other_coordinates[1]
variant["stop"] = other_position
# Set 'infinity' to length if translocation
variant["sv_len"] = float("inf")
else:
variant["stop"] = int(info_dict.get("END", variant_dict["POS"]))
variant["sv_len"] = variant["stop"] - variant["start"]
variant["stop_chrom"] = other_chrom
else:
variant["stop"] = int(variant_dict["POS"]) + (len(variant_dict["REF"]) - len(variant_dict["ALT"]))
variant["sv_type"] = info_dict.get("SVTYPE")
variant["cytoband_start"] = get_cytoband_coord(chrom=variant["CHROM"], pos=variant["start"])
if variant.get("stop_chrom"):
variant["cytoband_stop"] = get_cytoband_coord(chrom=variant["stop_chrom"], pos=variant["stop"])
# It would be easy to update these keys...
thousand_g = info_dict.get("1000GAF")
if thousand_g:
logger.debug("Updating thousand_g to: {0}".format(thousand_g))
variant["thousand_g"] = float(thousand_g)
variant.add_frequency("1000GAF", variant.get("thousand_g"))
# SV specific tag for number of occurances
occurances = info_dict.get("OCC")
if occurances:
logger.debug("Updating occurances to: {0}".format(occurances))
variant["occurances"] = float(occurances)
variant.add_frequency("OCC", occurances)
cadd_score = info_dict.get("CADD")
if cadd_score:
logger.debug("Updating cadd_score to: {0}".format(cadd_score))
variant["cadd_score"] = float(cadd_score)
rank_score_entry = info_dict.get("RankScore")
if rank_score_entry:
for family_annotation in rank_score_entry.split(","):
rank_score = family_annotation.split(":")[-1]
logger.debug("Updating rank_score to: {0}".format(rank_score))
variant["rank_score"] = float(rank_score)
genetic_models_entry = info_dict.get("GeneticModels")
if genetic_models_entry:
genetic_models = []
for family_annotation in genetic_models_entry.split(","):
for genetic_model in family_annotation.split(":")[-1].split("|"):
genetic_models.append(genetic_model)
logger.debug("Updating rank_score to: {0}".format(rank_score))
variant["genetic_models"] = genetic_models
# Add genotype calls:
for individual in case_obj.individuals:
sample_id = individual.ind_id
if sample_id in vcf_individuals:
raw_call = dict(zip(variant_dict["FORMAT"].split(":"), variant_dict[sample_id].split(":")))
variant.add_individual(
Genotype(
sample_id=sample_id,
genotype=raw_call.get("GT", "./."),
case_id=individual.case_name,
phenotype=individual.phenotype,
ref_depth=raw_call.get("AD", ",").split(",")[0],
alt_depth=raw_call.get("AD", ",").split(",")[1],
genotype_quality=raw_call.get("GQ", "."),
depth=raw_call.get("DP", "."),
supporting_evidence=raw_call.get("SU", "0"),
pe_support=raw_call.get("PE", "0"),
sr_support=raw_call.get("SR", "0"),
)
)
# Add transcript information:
gmaf = None
if vep_string:
for transcript_info in vep_info:
transcript = self._get_vep_transcripts(transcript_info)
gmaf_raw = transcript_info.get("GMAF")
if gmaf_raw:
gmaf = float(gmaf_raw.split(":")[-1])
variant.add_transcript(transcript)
if gmaf:
variant.add_frequency("GMAF", gmaf)
if not variant.thousand_g:
variant.thousand_g = gmaf
elif snpeff_string:
for transcript_info in snpeff_info:
transcript = self._get_snpeff_transcripts(transcript_info)
variant.add_transcript(transcript)
variant["most_severe_consequence"] = get_most_severe_consequence(variant["transcripts"])
for gene in self._get_genes(variant):
variant.add_gene(gene)
self._add_compounds(variant=variant, info_dict=info_dict)
yield variant
def cli(variant_file, thousand_g, exac, treshold, outfile, annotate, keyword,
verbose, logfile):
"""
Filter vcf variants based on their frequency.
One can use different sources by addind --keyword multiple times.
Variants and frequency sources should be splitted and normalized(with vt).
"""
loglevel = LEVELS.get(min(verbose,2), "WARNING")
init_log(root_logger, logfile, loglevel)
logger = logging.getLogger(__name__)
#For testing
logger = logging.getLogger("filter_variants.cli.root")
logger.info("Running filter_variants version {0}".format(__version__))
logger.info("Initializing a Header Parser")
head = HeaderParser()
for line in variant_file:
line = line.rstrip()
if line.startswith('#'):
if line.startswith('##'):
head.parse_meta_data(line)
else:
head.parse_header_line(line)
else:
break
if line:
variant_file = itertools.chain([line], variant_file)
if thousand_g:
logger.info("Opening 1000G frequency file with tabix open")
try:
thousand_g_handle = get_tabix_handle(thousand_g)
except OSError as e:
logger.critical(e.message)
logger.info("Exiting")
sys.exit(1)
logger.debug("1000G frequency file opened")
if annotate:
head.add_info(
"1000GAF",
"1",
'Float',
"Frequency in the 1000G database."
)
if exac:
logger.info("Opening ExAC frequency file with tabix open")
try:
exac_handle = get_tabix_handle(exac)
except OSError as e:
logger.critical(e.message)
logger.info("Exiting")
sys.exit(1)
logger.debug("ExAC frequency file opened")
if annotate:
head.add_info(
"ExACAF",
"1",
'Float',
"Frequency in the ExAC database."
)
plugins = []
for key in keyword:
if key not in head.info_dict:
logger.error("{0} is not defined in vcf header.".format(key))
logger.info("Exiting")
sys.exit(1)
plugins.append(Plugin(
name=key,
field='INFO',
data_type='float',
separators=[','],
info_key=key,
record_rule='max',
))
print_headers(head, outfile)
for line in variant_file:
max_freq = 0
line = line.rstrip()
variant_line = line.split('\t')
chrom = variant_line[0].strip('chr')
position = int(variant_line[1])
ref = variant_line[3]
alternative = variant_line[4]
logger.debug("Checking variant {0}".format(
'_'.join([chrom, str(position), ref, alternative])
))
for plugin in plugins:
logger.debug("Getting frequency for {0}".format(
plugin.name))
frequency = plugin.get_value(variant_line=line)
logger.debug("Found frequency {0}".format(
frequency))
if frequency:
if float(frequency) > max_freq:
logger.debug("Updating max freq")
max_freq = float(frequency)
if thousand_g:
logger.debug("Getting thousand g frequency")
frequency = get_frequency(
chrom = chrom,
pos = position,
alt = alternative,
tabix_reader = thousand_g_handle
)
logger.debug("Found frequency {0}".format(
frequency))
if frequency:
if annotate:
line = add_vcf_info(
keyword='1000GAF',
variant_line=line,
annotation=frequency
)
if float(frequency) > max_freq:
logger.debug("Updating max freq")
max_freq = float(frequency)
if exac:
logger.debug("Getting ExAC frequency")
frequency = get_frequency(
chrom = chrom,
pos = position,
alt = alternative,
tabix_reader = exac_handle
)
logger.debug("Found frequency {0}".format(
frequency))
if frequency:
if annotate:
line = add_vcf_info(
keyword='ExACAF',
variant_line=line,
annotation=frequency
)
if float(frequency) > max_freq:
logger.debug("Updating max freq")
max_freq = float(frequency)
if max_freq < treshold:
print_variant(line, outfile)
else:
logger.debug("Frequency {0} is higher than treshold"\
" {1}. Skip printing variant".format(max_freq, treshold))
def export(ctx, outfile):
"""Export the variants of a loqus db
The variants are exported to a vcf file
"""
adapter = ctx.obj['adapter']
logger.info("Export the variants from {0}".format(adapter))
nr_cases = 0
existing_chromosomes = set(adapter.get_chromosomes())
ordered_chromosomes = []
for chrom in CHROMOSOME_ORDER:
if chrom in existing_chromosomes:
ordered_chromosomes.append(chrom)
existing_chromosomes.remove(chrom)
for chrom in existing_chromosomes:
ordered_chromosomes.append(chrom)
nr_cases = adapter.cases().count()
logger.info("Found {0} cases in database".format(nr_cases))
head = HeaderParser()
head.add_fileformat("VCFv4.3")
head.add_meta_line("NrCases", nr_cases)
head.add_info("Obs", '1', 'Integer',
"The number of observations for the variant")
head.add_info("Hom", '1', 'Integer', "The number of observed homozygotes")
head.add_info("Hem", '1', 'Integer', "The number of observed hemizygotes")
head.add_version_tracking("loqusdb", __version__,
datetime.now().strftime("%Y-%m-%d %H:%M"))
for chrom in ordered_chromosomes:
length = adapter.get_max_position(chrom)
head.add_contig(contig_id=chrom, length=str(length))
print_headers(head, outfile=outfile)
for chrom in ordered_chromosomes:
for variant in adapter.get_variants(chromosome=chrom):
chrom = variant['chrom']
pos = variant['start']
ref = variant['ref']
alt = variant['alt']
observations = variant['observations']
homozygotes = variant['homozygote']
hemizygotes = variant['hemizygote']
info = "Obs={0}".format(observations)
if homozygotes:
info += ";Hom={0}".format(homozygotes)
if hemizygotes:
info += ";Hem={0}".format(hemizygotes)
variant_line = "{0}\t{1}\t.\t{2}\t{3}\t.\t.\t{4}\n".format(
chrom, pos, ref, alt, info)
print_variant(variant_line=variant_line, outfile=outfile)
def export(ctx, outfile, variant_type):
"""Export the variants of a loqus db
The variants are exported to a vcf file
"""
adapter = ctx.obj['adapter']
version = ctx.obj['version']
LOG.info("Export the variants from {0}".format(adapter))
nr_cases = 0
is_sv = variant_type == 'sv'
existing_chromosomes = set(adapter.get_chromosomes(sv=is_sv))
ordered_chromosomes = []
for chrom in CHROMOSOME_ORDER:
if chrom in existing_chromosomes:
ordered_chromosomes.append(chrom)
existing_chromosomes.remove(chrom)
for chrom in existing_chromosomes:
ordered_chromosomes.append(chrom)
nr_cases = adapter.cases().count()
LOG.info("Found {0} cases in database".format(nr_cases))
head = HeaderParser()
head.add_fileformat("VCFv4.3")
head.add_meta_line("NrCases", nr_cases)
head.add_info("Obs", '1', 'Integer', "The number of observations for the variant")
head.add_info("Hom", '1', 'Integer', "The number of observed homozygotes")
head.add_info("Hem", '1', 'Integer', "The number of observed hemizygotes")
head.add_version_tracking("loqusdb", version, datetime.now().strftime("%Y-%m-%d %H:%M"))
if variant_type == 'sv':
head.add_info("END", '1', 'Integer', "End position of the variant")
head.add_info("SVTYPE", '1', 'String', "Type of structural variant")
head.add_info("SVLEN", '1', 'Integer', "Length of structural variant")
for chrom in ordered_chromosomes:
length = adapter.get_max_position(chrom)
head.add_contig(contig_id=chrom, length=str(length))
print_headers(head, outfile=outfile)
for chrom in ordered_chromosomes:
if variant_type == 'snv':
LOG.info("Collecting all SNV variants")
variants = adapter.get_variants(chromosome=chrom)
else:
LOG.info("Collecting all SV variants")
variants = adapter.get_sv_variants(chromosome=chrom)
LOG.info("{} variants found".format(variants.count()))
for variant in variants:
variant_line = format_variant(variant, variant_type=variant_type)
# chrom = variant['chrom']
# pos = variant['start']
# ref = variant['ref']
# alt = variant['alt']
# observations = variant['observations']
# homozygotes = variant['homozygote']
# hemizygotes = variant['hemizygote']
# info = "Obs={0}".format(observations)
# if homozygotes:
# info += ";Hom={0}".format(homozygotes)
# if hemizygotes:
# info += ";Hem={0}".format(hemizygotes)
# variant_line = "{0}\t{1}\t.\t{2}\t{3}\t.\t.\t{4}\n".format(
# chrom, pos, ref, alt, info)
print_variant(variant_line=variant_line, outfile=outfile)
def export(ctx, outfile):
"""Export the variants of a loqus db
The variants are exported to a vcf file
"""
adapter = ctx.obj['adapter']
logger.info("Export the variants from {0}".format(adapter))
nr_cases = 0
for nr_cases, case in enumerate(adapter.cases()):
nr_cases += 1
logger.info("Found {0} cases in database".format(nr_cases))
head = HeaderParser()
head.add_fileformat("##fileformat=VCFv4.1")
head.add_meta_line("NrCases", nr_cases)
head.add_info("Obs", '1', 'Integer',
"The number of observations for the variant")
head.add_info("Hom", '1', 'Integer', "The number of observed homozygotes")
head.add_version_tracking("loqusdb", __version__,
datetime.now().strftime("%Y-%m-%d %H:%M"))
logger.debug("Create tempfile to print variants from database")
variants = tempfile.TemporaryFile()
logger.debug("Printing headers")
print_headers(head, outfile=outfile)
try:
for variant in adapter.get_variants():
variant_id = variant['_id'].split('_')
chrom = variant_id[0]
pos = variant_id[1]
ref = variant_id[2]
alt = variant_id[3]
observations = variant['observations']
homozygotes = variant['homozygote']
info = "Obs={0};Hom={1}".format(observations, homozygotes)
variant_line = "{0}\t{1}\t.\t{2}\t{3}\t.\t.\t{4}\n".format(
chrom, pos, ref, alt, info)
variants.write(variant_line)
variants.seek(0)
for line in sort_variants(variants):
print_variant(variant_line=line, outfile=outfile)
finally:
variants.close()
def get_individuals(vcf=None, case_lines=None, case_type='ped'):
"""Get the individuals from a vcf file, and/or a ped file.
Args:
vcf (str): Path to a vcf
case_lines(Iterable): Ped like lines
case_type(str): Format of ped lines
Returns:
individuals (generator): generator with Individuals
"""
individuals = []
if case_lines:
# read individuals from ped file
family_parser = FamilyParser(case_lines, family_type=case_type)
families = family_parser.families
logger.info("Found families {0}".format(
','.join(list(families.keys()))))
if len(families) != 1:
logger.error("Only one family can be used with vcf adapter")
raise IOError
case_id = list(families.keys())[0]
logger.info("Family used in analysis: {0}".format(case_id))
for ind_id in family_parser.individuals:
ind = family_parser.individuals[ind_id]
logger.info("Found individual {0}".format(ind.individual_id))
individual = Individual(
ind_id=ind.individual_id,
case_id=case_id,
mother=ind.mother,
father=ind.father,
sex=str(ind.sex),
phenotype=str(ind.phenotype),
variant_source=vcf,
)
individuals.append(individual)
elif vcf:
# read individuals from vcf file
case_id = os.path.basename(vcf)
head = HeaderParser()
handle = get_vcf_handle(infile=vcf)
for line in handle:
line = line.rstrip()
if line.startswith('#'):
if line.startswith('##'):
head.parse_meta_data(line)
else:
head.parse_header_line(line)
else:
break
for index, ind in enumerate(head.individuals):
# If we only have a vcf file we can not get metadata about the
# individuals
individual = Individual(
ind_id=ind,
case_id=case_id,
variant_source=vcf,
)
individuals.append(individual)
logger.debug("Found individual {0} in {1}".format(
ind, vcf))
return individuals
def export(ctx, outfile):
"""Export the variants of a loqus db
The variants are exported to a vcf file
"""
adapter = ctx.obj['adapter']
logger.info("Export the variants from {0}".format(adapter))
nr_cases = 0
for nr_cases, case in enumerate(adapter.cases()):
nr_cases += 1
logger.info("Found {0} cases in database".format(nr_cases))
head = HeaderParser()
head.add_fileformat("##fileformat=VCFv4.1")
head.add_meta_line("NrCases", nr_cases)
head.add_info("Obs", '1', 'Integer', "The number of observations for the variant")
head.add_info("Hom", '1', 'Integer', "The number of observed homozygotes")
head.add_version_tracking("loqusdb", __version__, datetime.now().strftime("%Y-%m-%d %H:%M"))
logger.debug("Create tempfile to print variants from database")
variants = tempfile.TemporaryFile()
logger.debug("Printing headers")
print_headers(head, outfile=outfile)
try:
for variant in adapter.get_variants():
variant_id = variant['_id'].split('_')
chrom = variant_id[0]
pos = variant_id[1]
ref = variant_id[2]
alt = variant_id[3]
observations = variant['observations']
homozygotes = variant['homozygote']
info = "Obs={0};Hom={1}".format(observations, homozygotes)
variant_line = "{0}\t{1}\t.\t{2}\t{3}\t.\t.\t{4}\n".format(
chrom, pos, ref, alt, info)
variants.write(variant_line)
variants.seek(0)
for line in sort_variants(variants):
print_variant(variant_line=line, outfile=outfile)
finally:
variants.close()
def _formated_variants(self, raw_variants, case_obj):
"""Return variant objects
Args:
raw_variants (Iterable): An iterable with variant lines
case_obj (puzzle.nodels.Case): A case object
"""
vcf_file_path = case_obj.variant_source
logger.info("Parsing file {0}".format(vcf_file_path))
head = HeaderParser()
handle = get_vcf_handle(infile=vcf_file_path)
# Parse the header
for line in handle:
line = line.rstrip()
if line.startswith('#'):
if line.startswith('##'):
head.parse_meta_data(line)
else:
head.parse_header_line(line)
else:
break
handle.close()
header_line = head.header
# Get the individual ids for individuals in vcf file
vcf_individuals = set([ind_id for ind_id in head.individuals])
variant_columns = ['CHROM', 'POS', 'ID', 'REF', 'ALT', 'QUAL', 'FILTER']
vep_header = head.vep_columns
snpeff_header = head.snpeff_columns
index = 0
for variant_line in raw_variants:
if not variant_line.startswith('#'):
index += 1
#Create a variant dict:
variant_dict = get_variant_dict(
variant_line = variant_line,
header_line = header_line
)
variant_dict['CHROM'] = variant_dict['CHROM'].lstrip('chrCHR')
#Crreate a info dict:
info_dict = get_info_dict(
info_line = variant_dict['INFO']
)
#Check if vep annotation:
vep_string = info_dict.get('CSQ')
#Check if snpeff annotation:
snpeff_string = info_dict.get('ANN')
if vep_string:
#Get the vep annotations
vep_info = get_vep_info(
vep_string = vep_string,
vep_header = vep_header
)
elif snpeff_string:
#Get the vep annotations
snpeff_info = get_snpeff_info(
snpeff_string = snpeff_string,
snpeff_header = snpeff_header
)
variant = Variant(
**{column: variant_dict.get(column, '.')
for column in variant_columns}
)
logger.debug("Creating a variant object of variant {0}".format(
variant.get('variant_id')))
variant['index'] = index
logger.debug("Updating index to: {0}".format(
index))
variant['start'] = int(variant_dict['POS'])
if self.variant_type == 'sv':
other_chrom = variant['CHROM']
# If we have a translocation:
if ':' in variant_dict['ALT']:
other_coordinates = variant_dict['ALT'].strip('ACGTN[]').split(':')
other_chrom = other_coordinates[0].lstrip('chrCHR')
other_position = other_coordinates[1]
variant['stop'] = other_position
#Set 'infinity' to length if translocation
variant['sv_len'] = float('inf')
else:
variant['stop'] = int(info_dict.get('END', variant_dict['POS']))
variant['sv_len'] = variant['stop'] - variant['start']
variant['stop_chrom'] = other_chrom
else:
variant['stop'] = int(variant_dict['POS']) + \
(len(variant_dict['REF']) - len(variant_dict['ALT']))
variant['sv_type'] = info_dict.get('SVTYPE')
variant['cytoband_start'] = get_cytoband_coord(
chrom=variant['CHROM'],
pos=variant['start'])
if variant.get('stop_chrom'):
variant['cytoband_stop'] = get_cytoband_coord(
chrom=variant['stop_chrom'],
pos=variant['stop'])
# It would be easy to update these keys...
thousand_g = info_dict.get('1000GAF')
if thousand_g:
logger.debug("Updating thousand_g to: {0}".format(
thousand_g))
variant['thousand_g'] = float(thousand_g)
variant.add_frequency('1000GAF', variant.get('thousand_g'))
#SV specific tag for number of occurances
occurances = info_dict.get('OCC')
if occurances:
logger.debug("Updating occurances to: {0}".format(
occurances))
variant['occurances'] = float(occurances)
variant.add_frequency('OCC', occurances)
cadd_score = info_dict.get('CADD')
if cadd_score:
logger.debug("Updating cadd_score to: {0}".format(
cadd_score))
variant['cadd_score'] = float(cadd_score)
rank_score_entry = info_dict.get('RankScore')
if rank_score_entry:
for family_annotation in rank_score_entry.split(','):
rank_score = family_annotation.split(':')[-1]
logger.debug("Updating rank_score to: {0}".format(
rank_score))
variant['rank_score'] = float(rank_score)
genetic_models_entry = info_dict.get('GeneticModels')
if genetic_models_entry:
genetic_models = []
for family_annotation in genetic_models_entry.split(','):
for genetic_model in family_annotation.split(':')[-1].split('|'):
genetic_models.append(genetic_model)
logger.debug("Updating rank_score to: {0}".format(
rank_score))
variant['genetic_models'] = genetic_models
#Add genotype calls:
for individual in case_obj.individuals:
sample_id = individual.ind_id
if sample_id in vcf_individuals:
raw_call = dict(zip(
variant_dict['FORMAT'].split(':'),
variant_dict[sample_id].split(':'))
)
variant.add_individual(Genotype(
sample_id = sample_id,
genotype = raw_call.get('GT', './.'),
case_id = individual.case_name,
phenotype = individual.phenotype,
ref_depth = raw_call.get('AD', ',').split(',')[0],
alt_depth = raw_call.get('AD', ',').split(',')[1],
genotype_quality = raw_call.get('GQ', '.'),
depth = raw_call.get('DP', '.'),
supporting_evidence = raw_call.get('SU', '0'),
pe_support = raw_call.get('PE', '0'),
sr_support = raw_call.get('SR', '0'),
))
# Add transcript information:
if vep_string:
for transcript in self._get_vep_transcripts(variant, vep_info):
variant.add_transcript(transcript)
elif snpeff_string:
for transcript in self._get_snpeff_transcripts(variant, snpeff_info):
variant.add_transcript(transcript)
variant['most_severe_consequence'] = get_most_severe_consequence(
variant['transcripts']
)
for gene in self._get_genes(variant):
variant.add_gene(gene)
self._add_compounds(variant=variant, info_dict=info_dict)
yield variant
