def test_is_lof(self):
""" test that is_lof() works correctly
"""
# check that known LOF consensequence return True
info = Info('CQ=stop_gained;HGNC=TEST')
info.set_genes_and_consequence('1', 100, ('G'), [])
self.assertTrue(info.is_lof())
# check that known non-LOF consensequence returns False
info = Info('CQ=missense_variant;HGNC=TEST')
info.set_genes_and_consequence('1', 100, ('G'), [])
self.assertFalse(info.is_lof())
# check that null values return False
info = Info('HGNC=TEST')
info.set_genes_and_consequence('1', 100, ('G'), [])
self.assertFalse(info.is_lof())
# check when the variant overlaps multiple genes (so has multiple
# gene symbols and consequences).
info = Info('CQ=stop_gained|missense_variant;HGNC=ATRX|TTN')
info.set_genes_and_consequence('1', 100, ('G'), [])
self.assertTrue(info.is_lof())
self.assertTrue(info.is_lof("ATRX"))
self.assertFalse(info.is_lof("TTN"))
# check that when we have a MNV, we can lose or gain a LOF annotation
info.mnv_code = 'masked_stop_gain_mnv'
self.assertFalse(info.is_lof("ATRX"))
info.mnv_code = 'modified_stop_gained_mnv'
self.assertTrue(info.is_lof("TTN"))
def test_is_lof(self):
""" test that is_lof() works correctly
"""
# check that known LOF consensequence return True
info = Info('CQ=stop_gained;HGNC=TEST')
info.set_genes_and_consequence('1', 100, ('G'), [])
self.assertTrue(info.is_lof())
# check that known non-LOF consensequence returns False
info = Info('CQ=missense_variant;HGNC=TEST')
info.set_genes_and_consequence('1', 100, ('G'), [])
self.assertFalse(info.is_lof())
# check that null values return False
info = Info('HGNC=TEST')
info.set_genes_and_consequence('1', 100, ('G'), [])
self.assertFalse(info.is_lof())
# check when the variant overlaps multiple genes (so has multiple
# gene symbols and consequences).
info = Info('CQ=stop_gained|missense_variant;HGNC=ATRX|TTN')
info.set_genes_and_consequence('1', 100, ('G'), [])
self.assertTrue(info.is_lof())
self.assertTrue(info.is_lof("ATRX"))
self.assertFalse(info.is_lof("TTN"))
# check that when we have a MNV, we can lose or gain a LOF annotation
info.mnv_code = 'masked_stop_gain_mnv'
self.assertFalse(info.is_lof("ATRX"))
info.mnv_code = 'modified_stop_gained_mnv'
self.assertTrue(info.is_lof("TTN"))
class Variant(object):
""" generic functions for variants
"""
# define some codes used in ped files to identify male and female sexes
male_codes = set(["1", "m", "M", "male"])
female_codes = set(["2", "f", "F", "female"])
x_pseudoautosomal_regions = [(60001, 2699520), (154930290, 155260560), \
(88456802, 92375509)]
y_pseudoautosomal_regions = [(10001, 2649520), (59034050, 59363566)]
known_genes = None
@classmethod
def set_known_genes(cls_obj, known_genes):
cls_obj.known_genes = known_genes
def __init__(self, chrom, position, id, ref, alts, qual, filter, info=None,
format=None, sample=None, gender=None, sum_x_lr2=None, parents=None, mnv_code=None):
""" initialise the object with the definition values
"""
self.chrom = chrom
self.position = int(position)
self.variant_id = id
self.mutation_id = "NA"
self.set_mutation_id(self.variant_id)
self.ref_allele = ref
self.alt_alleles = tuple(alts.split(','))
self.mnv_code = mnv_code
self.qual = qual
self.filter = filter
self.sum_x_lr2 = sum_x_lr2
self.has_parents = parents
# intialise variables that will be set later
self.inheritance_type = None
self.gender = None
if gender is not None:
self._set_gender(gender)
self.vcf_line = None
self.format = None
if format is not None and sample is not None:
self.add_format(format, sample)
self.info = Info(info, self.mnv_code)
masked = self.get_low_depth_alleles(self.ref_allele, self.alt_alleles)
self.info.set_genes_and_consequence(self.get_chrom(),
self.get_position(), self.alt_alleles, masked)
self.genotype = None
if self.format is not None and self._get_gender() is not None:
self.set_genotype()
def is_lof(self, gene_symbol=None):
return self.info.is_lof(gene_symbol)
def is_missense(self, is_cnv, gene_symbol=None):
return self.info.is_missense(is_cnv, gene_symbol)
def is_synoymous(self, gene_symbol=None):
return self.info.is_synoymous(gene_symbol)
def __repr__(self):
''' repr function for Variant objects. SNV(...) and CNV(...) also work
'''
def quote(value):
if value is not None:
value = '"{}"'.format(value)
return value
# reprocess the format dictionary back to the original text strings
keys, sample = None, None
if self.format is not None:
keys = quote(':'.join(sorted(self.format)))
sample = quote(':'.join([ self.format[x] for x in sorted(self.format) ]))
info = quote(self.info)
gender = quote(self.gender)
mnv_code = quote(self.mnv_code)
return '{}(chrom="{}", position={}, id="{}", ref="{}", alts="{}", ' \
'qual="{}", filter="{}", info={}, format={}, sample={}, gender={}, ' \
'mnv_code={})'.format(type(self).__name__, self.chrom,
self.position, self.variant_id, self.ref_allele,
','.join(self.alt_alleles), self.qual, self.filter, info, keys, sample,
gender, mnv_code)
def __hash__(self):
return hash(str(self))
def __eq__(self, other):
return hash(self) == hash(other)
def _set_gender(self, gender):
""" sets the gender of the individual for the variant
"""
if gender in self.male_codes:
self.gender = "male"
elif gender in self.female_codes:
self.gender = "female"
else:
raise ValueError("unknown gender code")
self.set_inheritance_type(self.get_position(), self.is_male())
def _get_gender(self):
"""returns the gender for a person (1, M = male, 2, F = female).
"""
return self.gender
def set_mutation_id(self, variant_id):
""" sets the mutation ID based on the VCF ID field
The variant ID can be either "." for null value, an rsID, a HGMD ID,
a COSMIC ID, or any combination of those (including multiple HGMD IDs
for a single variant).
Args:
variant_id: string from the VCF ID field, can be rsID, or a list of
&-separated IDs, which can include COSMIC and HGMD IDs.
"""
if variant_id != ".":
variant_id = variant_id.split("&")
ids = []
for value in variant_id:
# include everything that isn't an rsID
if not value.startswith("rs"):
ids.append(value)
if len(ids) > 0:
self.mutation_id = ",".join(ids)
def get_mutation_id(self):
return self.mutation_id
def is_male(self):
""" returns True/False for whether the person is male
"""
return self._get_gender() in self.male_codes
def add_format(self, keys, values):
"""Parses the FORMAT column from VCF files.
Args:
keys: FORMAT text from a line in a VCF file
values: the values for the format keys
"""
self.format = dict(zip(keys.split(":"), values.split(":")))
def get_low_depth_alleles(self, ref, alts):
''' get a list of alleles with zero counts, or indels with 1 read
Some variants have multiple alts, so we need to select the alt with
the most severe consequence. However, in at least one version of the
VCFs, one of the alts could have zero counts, which I believe resulted
from the population based multi-sample calling. We need to drop the
consequences recorded for zero-count alternate alleles before finding
the most severe.
We also want to avoid indels with only one read, because these are
universally bad calls.
Args:
ref: reference allele
alts: tuple of alt alleles
Returns:
list of alleles with sufficiently low depth
'''
is_indel = lambda x, y: len(x) > 1 or len(y) > 1
allele_counts = ['1'] * len(alts)
if 'AC' in self.info:
allele_counts = self.info['AC'].split(',')
allele_depths = ['10'] * len(alts)
if 'AD' in self.format:
allele_depths = self.format['AD'].split(',')[1:]
counts = list(zip(allele_counts, allele_depths))
assert len(counts) == len(alts)
# find the positions of alleles where the allele count is zero,
# or indels with 1 alt read
pos = set()
for i, (count, depth) in enumerate(counts):
if count == '0':
pos.add(i)
elif depth == '1' and is_indel(ref, alts[i]):
pos.add(i)
# return the alleles with zero-count ,so we can mask them out
return [ alts[i] for i in sorted(pos) ]
def add_vcf_line(self, vcf_line):
self.vcf_line = vcf_line
def get_vcf_line(self):
return self.vcf_line
def set_inheritance_type(self, pos, is_male):
""" sets the chromosome type (eg autosomal, or X chromosome type).
provides the chromosome type for a chromosome (eg Autosomal, or
X-chrom male etc). This only does simple string matching. The
chromosome string is either the chromosome number, or in the case of
the sex-chromosomes, the chromosome character. This doesn't allow for
chromosomes to be specified as "chr1", and sex chromosomes have to be
specified as "X" or "Y", not "23" or "24".
Args:
pos: position on the chromosome
is_male: True/False for whether the individual is male
"""
if self.get_chrom() not in ["chrX", "ChrX", "X", "chrY", "ChrY", "Y"]:
self.inheritance_type = "autosomal"
elif self.get_chrom() in ["chrX", "ChrX", "X"]:
# check if the gene lies within a pseudoautosomal region
for start, end in self.x_pseudoautosomal_regions:
if start < pos < end:
self.inheritance_type = "autosomal"
return
if is_male:
self.inheritance_type = "XChrMale"
else:
self.inheritance_type = "XChrFemale"
elif self.get_chrom() in ["chrY", "ChrY", "Y"]:
# check if the gene lies within a pseudoautosomal region
for start, end in self.y_pseudoautosomal_regions:
if start < pos < end:
self.inheritance_type = "autosomal"
return
if is_male:
self.inheritance_type = "YChrMale"
else:
self.inheritance_type = "YChrFemale"
def get_inheritance_type(self):
""" return the variant chromosomal inheritance type
"""
return self.inheritance_type
def get_chrom(self):
""" return the variant chromosome
"""
return self.chrom
def get_position(self):
""" return the variant chromosomal position
"""
return self.position
def get_genotype(self):
""" return the genotype value
"""
return self.genotype
def get_sum_x_lr2(self):
""" return the sum of mean l2r on x chromsome
"""
return self.sum_x_lr2
def get_has_parents(self):
"""returns false for singletons, true for trios
"""
return self.has_parents
class Variant(object):
""" generic functions for variants
"""
# define some codes used in ped files to identify male and female sexes
male_codes = set(["1", "m", "M", "male"])
female_codes = set(["2", "f", "F", "female"])
x_pseudoautosomal_regions = [(60001, 2699520), (154930290, 155260560), \
(88456802, 92375509)]
y_pseudoautosomal_regions = [(10001, 2649520), (59034050, 59363566)]
known_genes = None
@classmethod
def set_known_genes(cls_obj, known_genes):
cls_obj.known_genes = known_genes
def __init__(self,
chrom,
position,
id,
ref,
alts,
qual,
filter,
info=None,
format=None,
sample=None,
gender=None,
sum_x_lr2=None,
parents=None,
mnv_code=None):
""" initialise the object with the definition values
"""
self.chrom = chrom
self.position = int(position)
self.variant_id = id
self.mutation_id = "NA"
self.set_mutation_id(self.variant_id)
self.ref_allele = ref
self.alt_alleles = tuple(alts.split(','))
self.mnv_code = mnv_code
self.qual = qual
self.filter = filter
self.sum_x_lr2 = sum_x_lr2
self.has_parents = parents
# intialise variables that will be set later
self.inheritance_type = None
self.gender = None
if gender is not None:
self._set_gender(gender)
self.vcf_line = None
self.format = None
if format is not None and sample is not None:
self.add_format(format, sample)
self.info = Info(info, self.mnv_code)
masked = self.get_low_depth_alleles(self.ref_allele, self.alt_alleles)
self.info.set_genes_and_consequence(self.get_chrom(),
self.get_position(),
self.alt_alleles, masked)
self.genotype = None
if self.format is not None and self._get_gender() is not None:
self.set_genotype()
def is_lof(self, gene_symbol=None):
return self.info.is_lof(gene_symbol)
def is_missense(self, is_cnv, gene_symbol=None):
return self.info.is_missense(is_cnv, gene_symbol)
def is_synoymous(self, gene_symbol=None):
return self.info.is_synoymous(gene_symbol)
def __repr__(self):
''' repr function for Variant objects. SNV(...) and CNV(...) also work
'''
def quote(value):
if value is not None:
value = '"{}"'.format(value)
return value
# reprocess the format dictionary back to the original text strings
keys, sample = None, None
if self.format is not None:
keys = quote(':'.join(sorted(self.format)))
sample = quote(':'.join(
[self.format[x] for x in sorted(self.format)]))
info = quote(self.info)
gender = quote(self.gender)
mnv_code = quote(self.mnv_code)
return '{}(chrom="{}", position={}, id="{}", ref="{}", alts="{}", ' \
'qual="{}", filter="{}", info={}, format={}, sample={}, gender={}, ' \
'mnv_code={})'.format(type(self).__name__, self.chrom,
self.position, self.variant_id, self.ref_allele,
','.join(self.alt_alleles), self.qual, self.filter, info, keys, sample,
gender, mnv_code)
def __hash__(self):
return hash(str(self))
def __eq__(self, other):
return hash(self) == hash(other)
def _set_gender(self, gender):
""" sets the gender of the individual for the variant
"""
if gender in self.male_codes:
self.gender = "male"
elif gender in self.female_codes:
self.gender = "female"
else:
raise ValueError("unknown gender code")
self.set_inheritance_type(self.get_position(), self.is_male())
def _get_gender(self):
"""returns the gender for a person (1, M = male, 2, F = female).
"""
return self.gender
def set_mutation_id(self, variant_id):
""" sets the mutation ID based on the VCF ID field
The variant ID can be either "." for null value, an rsID, a HGMD ID,
a COSMIC ID, or any combination of those (including multiple HGMD IDs
for a single variant).
Args:
variant_id: string from the VCF ID field, can be rsID, or a list of
&-separated IDs, which can include COSMIC and HGMD IDs.
"""
if variant_id != ".":
variant_id = variant_id.split("&")
ids = []
for value in variant_id:
# include everything that isn't an rsID
if not value.startswith("rs"):
ids.append(value)
if len(ids) > 0:
self.mutation_id = ",".join(ids)
def get_mutation_id(self):
return self.mutation_id
def is_male(self):
""" returns True/False for whether the person is male
"""
return self._get_gender() in self.male_codes
def add_format(self, keys, values):
"""Parses the FORMAT column from VCF files.
Args:
keys: FORMAT text from a line in a VCF file
values: the values for the format keys
"""
self.format = dict(zip(keys.split(":"), values.split(":")))
def get_low_depth_alleles(self, ref, alts):
''' get a list of alleles with zero counts, or indels with 1 read
Some variants have multiple alts, so we need to select the alt with
the most severe consequence. However, in at least one version of the
VCFs, one of the alts could have zero counts, which I believe resulted
from the population based multi-sample calling. We need to drop the
consequences recorded for zero-count alternate alleles before finding
the most severe.
We also want to avoid indels with only one read, because these are
universally bad calls.
Args:
ref: reference allele
alts: tuple of alt alleles
Returns:
list of alleles with sufficiently low depth
'''
is_indel = lambda x, y: len(x) > 1 or len(y) > 1
allele_counts = ['1'] * len(alts)
if 'AC' in self.info:
allele_counts = self.info['AC'].split(',')
allele_depths = ['10'] * len(alts)
if 'AD' in self.format:
allele_depths = self.format['AD'].split(',')[1:]
counts = list(zip(allele_counts, allele_depths))
assert len(counts) == len(alts)
# find the positions of alleles where the allele count is zero,
# or indels with 1 alt read
pos = set()
for i, (count, depth) in enumerate(counts):
if count == '0':
pos.add(i)
elif depth == '1' and is_indel(ref, alts[i]):
pos.add(i)
# return the alleles with zero-count ,so we can mask them out
return [alts[i] for i in sorted(pos)]
def add_vcf_line(self, vcf_line):
self.vcf_line = vcf_line
def get_vcf_line(self):
return self.vcf_line
def set_inheritance_type(self, pos, is_male):
""" sets the chromosome type (eg autosomal, or X chromosome type).
provides the chromosome type for a chromosome (eg Autosomal, or
X-chrom male etc). This only does simple string matching. The
chromosome string is either the chromosome number, or in the case of
the sex-chromosomes, the chromosome character. This doesn't allow for
chromosomes to be specified as "chr1", and sex chromosomes have to be
specified as "X" or "Y", not "23" or "24".
Args:
pos: position on the chromosome
is_male: True/False for whether the individual is male
"""
if self.get_chrom() not in ["chrX", "ChrX", "X", "chrY", "ChrY", "Y"]:
self.inheritance_type = "autosomal"
elif self.get_chrom() in ["chrX", "ChrX", "X"]:
# check if the gene lies within a pseudoautosomal region
for start, end in self.x_pseudoautosomal_regions:
if start < pos < end:
self.inheritance_type = "autosomal"
return
if is_male:
self.inheritance_type = "XChrMale"
else:
self.inheritance_type = "XChrFemale"
elif self.get_chrom() in ["chrY", "ChrY", "Y"]:
# check if the gene lies within a pseudoautosomal region
for start, end in self.y_pseudoautosomal_regions:
if start < pos < end:
self.inheritance_type = "autosomal"
return
if is_male:
self.inheritance_type = "YChrMale"
else:
self.inheritance_type = "YChrFemale"
def get_inheritance_type(self):
""" return the variant chromosomal inheritance type
"""
return self.inheritance_type
def get_chrom(self):
""" return the variant chromosome
"""
return self.chrom
def get_position(self):
""" return the variant chromosomal position
"""
return self.position
def get_genotype(self):
""" return the genotype value
"""
return self.genotype
def get_sum_x_lr2(self):
""" return the sum of mean l2r on x chromsome
"""
return self.sum_x_lr2
def get_has_parents(self):
"""returns false for singletons, true for trios
"""
return self.has_parents
