def test_get_parental_var_snv(self):
''' check that get_parental_var() works correctly for SNVs
'''
sex = 'F'
var = create_snv(sex, '0/1')
mom = Person('fam_id', 'mom', '0', '0', 'F', '1', '/PATH')
parental = []
# try to get a matching variant for a mother. This will create a default
# variant for a missing parental genotype
self.assertEqual(
get_parental_var(var, parental, mom),
SNV(chrom="1",
position=150,
id=".",
ref="A",
alts="G",
qual='1000',
filter="PASS",
info=str(var.info),
format="GT",
sample="0/0",
gender="female",
mnv_code=None))
# now see if we can pick up a variant where it does exist
mother_var = create_snv(sex, '0/0')
self.assertEqual(get_parental_var(var, [mother_var], mom), mother_var)
def setUp(self):
""" define a family and variant, and start the Autosomal class
"""
# generate a test family
sex = "F"
mom_aff = "1"
dad_aff = "1"
self.trio = self.create_family(sex, mom_aff, dad_aff)
# generate a test variant
child = create_snv(sex, "0/1")
mom = create_snv("F", "0/0")
dad = create_snv("M", "0/0")
var = TrioGenotypes(child.get_chrom(), child.get_position(), child,
mom, dad)
self.variants = [var]
# make sure we've got known genes data
self.known_gene = {
"inh": ["Monoallelic"],
"confirmed_status": ["confirmed dd gene"]
}
self.inh = Autosomal(self.variants, self.trio, self.known_gene, "1001")
self.inh.is_lof = var.child.is_lof()
def test_check_variant_without_parents_female(self):
""" test that check_variant_without_parents() works correctly for female
"""
var = TrioGenotypes('X', 100, create_snv('F', "1/0"), None, None)
self.inh.set_trio_genotypes(var)
# check for X-linked dominant inheritance
self.assertEqual(self.inh.check_variant_without_parents("X-linked dominant"), "single_variant")
self.assertEqual(self.inh.log_string, "allosomal without parents")
var = TrioGenotypes('X', 100, create_snv('F', "1/1"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_variant_without_parents("X-linked dominant"), "single_variant")
# and check for hemizygous inheritance
var = TrioGenotypes('X', 100, create_snv('F', "1/0"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_variant_without_parents("Hemizygous"), "hemizygous")
var = TrioGenotypes('X', 100, create_snv('F', "1/1"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_variant_without_parents("Hemizygous"), "single_variant")
def test_check_variant_without_parents_female(self):
""" test that check_variant_without_parents() works correctly for female
"""
var = TrioGenotypes('X', 100, create_snv('F', "1/0"), None, None)
self.inh.set_trio_genotypes(var)
# check for X-linked dominant inheritance
self.assertEqual(
self.inh.check_variant_without_parents("X-linked dominant"),
"single_variant")
self.assertEqual(self.inh.log_string, "allosomal without parents")
var = TrioGenotypes('X', 100, create_snv('F', "1/1"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(
self.inh.check_variant_without_parents("X-linked dominant"),
"single_variant")
# and check for hemizygous inheritance
var = TrioGenotypes('X', 100, create_snv('F', "1/0"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_variant_without_parents("Hemizygous"),
"hemizygous")
var = TrioGenotypes('X', 100, create_snv('F', "1/1"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_variant_without_parents("Hemizygous"),
"single_variant")
def setUp(self):
""" define a family and variant, and start the Allosomal class
"""
# generate a test family
child_gender = "F"
mom_aff = "1"
dad_aff = "1"
self.trio = self.create_family(child_gender, mom_aff, dad_aff)
# generate a test variant
child = create_snv(child_gender,
"0/1",
chrom='X',
pos=150,
extra_info='HGNC=TEST;MAX_AF=0.0005')
mom = create_snv("F", "0/0", chrom='X', pos=150)
dad = create_snv("M", "0/0", chrom='X', pos=150)
self.variants = [TrioGenotypes('X', '150', child, mom, dad)]
self.report = Report(None, None, None)
Info.set_populations([
"AFR_AF", "AMR_AF", "ASN_AF", "DDD_AF", "EAS_AF", "ESP_AF",
"EUR_AF", "MAX_AF", "SAS_AF", "UK10K_cohort_AF"
])
def create_var(self, chrom='1', position='150', sex='F', child_geno='0/1'):
''' generate a test variant
'''
child = create_snv(sex, child_geno, chrom=chrom, pos=position)
mom = create_snv("F", "0/0", chrom=chrom, pos=position)
dad = create_snv("M", "0/0", chrom=chrom, pos=position)
return TrioGenotypes(child.get_chrom(), child.get_position(), child,
mom, dad)
def create_var(self, chrom='1', position='150', sex='F', child_geno='0/1'):
''' generate a test variant
'''
child = create_snv(sex, child_geno, chrom=chrom, pos=position)
mom = create_snv("F", "0/0", chrom=chrom, pos=position)
dad = create_snv("M", "0/0", chrom=chrom, pos=position)
return TrioGenotypes(child.get_chrom(), child.get_position(),
child, mom, dad)
def create_variant(self, chrom="1", position="150", sex='F', cq=None,
geno=['0/1', '0/0', '0/0']):
""" creates a TrioGenotypes variant
"""
# generate a test variant
child = create_snv(sex, geno[0], cq, chrom=chrom, pos=position)
mom = create_snv("F", geno[1], cq, chrom=chrom, pos=position)
dad = create_snv("M", geno[2], cq, chrom=chrom, pos=position)
return TrioGenotypes(chrom, position, child, mom, dad)
def test_check_homozygous_male(self):
""" test that check_homozygous() works correctly for males
"""
# check for trio with de novo on male X chrom
var = TrioGenotypes('X', 100, create_snv('M', "1/1"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
trio = self.create_family('male', '1', '1')
self.inh = Allosomal([var], trio, self.known_gene, "TEST")
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_homozygous("X-linked dominant"),
"single_variant")
self.assertEqual(self.inh.log_string, "male X chrom de novo")
# check for trio = 210, with unaffected mother
var = TrioGenotypes('X', 100, create_snv('M', "1/1"),
create_snv('F', "1/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_homozygous("X-linked dominant"),
"single_variant")
self.assertEqual(
self.inh.log_string,
"male X chrom inherited from het mother or hom affected mother")
# check for trio = 210, with affected mother, which should also pass
self.inh.mother_affected = True
self.assertEqual(self.inh.check_homozygous("X-linked dominant"),
"single_variant")
self.assertEqual(
self.inh.log_string,
"male X chrom inherited from het mother or hom affected mother")
# check for trio = 220, with affected mother
var = TrioGenotypes('X', 100, create_snv('M', "1/1"),
create_snv('F', "1/1"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_homozygous("X-linked dominant"),
"single_variant")
self.assertEqual(
self.inh.log_string,
"male X chrom inherited from het mother or hom affected mother")
# check for trio = 220, with unaffected mother, which should not pass
self.inh.mother_affected = False
self.assertEqual(self.inh.check_homozygous("X-linked dominant"),
"nothing")
self.assertEqual(self.inh.log_string,
"variant not compatible with being causal")
# check that homozygous X-linked over-dominance doesn't pass
self.assertEqual(self.inh.check_homozygous("X-linked over-dominance"),
'nothing')
# check we raise errors with unknown inheritance modes
with self.assertRaises(ValueError):
self.inh.check_homozygous("Digenic")
def create_variant(self,
chrom="1",
position="150",
sex='F',
cq=None,
geno=['0/1', '0/0', '0/0']):
""" creates a TrioGenotypes variant
"""
# generate a test variant
child = create_snv(sex, geno[0], cq, chrom=chrom, pos=position)
mom = create_snv("F", geno[1], cq, chrom=chrom, pos=position)
dad = create_snv("M", geno[2], cq, chrom=chrom, pos=position)
return TrioGenotypes(chrom, position, child, mom, dad)
def test_get_parental_var_snv(self):
''' check that get_parental_var() works correctly for SNVs
'''
sex = 'F'
var = create_snv(sex, '0/1')
mom = Person('fam_id', 'mom', '0', '0', 'F', '1', '/PATH')
parental = []
# try to get a matching variant for a mother. This will create a default
# variant for a missing parental genotype
self.assertEqual(self.vcf_loader.get_parental_var(var, parental, mom),
SNV(chrom="1", position=150, id=".", ref="A", alts="G",
filter="PASS", info=var.get_info_as_string(), format="GT", sample="0/0",
gender="female", mnv_code=None))
# now see if we can pick up a variant where it does exist
mother_var = create_snv(sex, '0/0')
self.assertEqual(self.vcf_loader.get_parental_var(var, [mother_var],
mom), mother_var)
def test_check_homozygous_male(self):
""" test that check_homozygous() works correctly for males
"""
# check for trio with de novo on male X chrom
var = TrioGenotypes('X', 100, create_snv('M', "1/1"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
trio = self.create_family('male', '1', '1')
self.inh = Allosomal([var], trio, self.known_gene, "TEST")
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_homozygous("X-linked dominant"), "single_variant")
self.assertEqual(self.inh.log_string, "male X chrom de novo")
# check for trio = 210, with unaffected mother
var = TrioGenotypes('X', 100, create_snv('M', "1/1"),
create_snv('F', "1/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_homozygous("X-linked dominant"), "single_variant")
self.assertEqual(self.inh.log_string, "male X chrom inherited from het mother or hom affected mother")
# check for trio = 210, with affected mother, which should also pass
self.inh.mother_affected = True
self.assertEqual(self.inh.check_homozygous("X-linked dominant"), "single_variant")
self.assertEqual(self.inh.log_string, "male X chrom inherited from het mother or hom affected mother")
# check for trio = 220, with affected mother
var = TrioGenotypes('X', 100, create_snv('M', "1/1"),
create_snv('F', "1/1"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_homozygous("X-linked dominant"), "single_variant")
self.assertEqual(self.inh.log_string, "male X chrom inherited from het mother or hom affected mother")
# check for trio = 220, with unaffected mother, which should not pass
self.inh.mother_affected = False
self.assertEqual(self.inh.check_homozygous("X-linked dominant"), "nothing")
self.assertEqual(self.inh.log_string, "variant not compatible with being causal")
# check that homozygous X-linked over-dominance doesn't pass
self.assertEqual(self.inh.check_homozygous("X-linked over-dominance"), 'nothing')
# check we raise errors with unknown inheritance modes
with self.assertRaises(ValueError):
self.inh.check_homozygous("Digenic")
def test_check_heterozygous_affected_father(self):
""" test that check_heterozygous() works correctly for affected fathers
"""
# set the father as non-ref genotype and unaffected
var = TrioGenotypes('X', 100, create_snv('F', "1/0"),
create_snv('F', "0/0"), create_snv('M', "1/1"))
self.inh.set_trio_genotypes(var)
# check that the het proband, with het unaffected father is passes
self.assertEqual(self.inh.check_heterozygous("X-linked dominant"), "nothing")
self.assertEqual(self.inh.log_string, "variant not compatible with being causal")
# check that the het proband, with het affected father is captured
self.inh.father_affected = True
self.assertEqual(self.inh.check_heterozygous("X-linked dominant"), "single_variant")
self.assertEqual(self.inh.log_string, "x chrom transmitted from aff, other parent non-carrier or aff")
# check that when the other parent is also non-ref, the variant is no
# longer captured, unless the parent is affected
var = TrioGenotypes('X', 100, create_snv('F', "1/0"),
create_snv('F', "1/0"), create_snv('M', "1/1"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_heterozygous("X-linked dominant"), "nothing")
self.assertEqual(self.inh.log_string, "variant not compatible with being causal")
self.inh.mother_affected = True
self.inh.check_heterozygous("X-linked dominant")
self.assertEqual(self.inh.log_string, "x chrom transmitted from aff, other parent non-carrier or aff")
def test_check_heterozygous_de_novo(self):
""" test that check_heterozygous() works correctly for de novos
"""
# all of these tests are run for female X chrom de novos, since male
# X chrom hets don't exist
var = TrioGenotypes('X', 100, create_snv('F', "1/0"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
# check for X-linked dominant inheritance
self.assertEqual(self.inh.check_heterozygous("X-linked dominant"), "single_variant")
self.assertEqual(self.inh.log_string, "female x chrom de novo")
# check for biallelic inheritance
self.assertEqual(self.inh.check_heterozygous("Hemizygous"), "single_variant")
# check for X-linked over dominance
self.assertEqual(self.inh.check_heterozygous("X-linked over-dominance"), 'single_variant')
# check we raise errors with unknown inheritance modes
with self.assertRaises(ValueError):
self.inh.check_heterozygous("Digenic")
genos = {'0': '0/0', '1': '1/0', '2': '1/1'}
for (child, mom, dad) in ["102", "110", "112", "122"]:
var = TrioGenotypes('X', 100, create_snv('F', genos[child]),
create_snv('F', genos[mom]), create_snv('M', genos[dad]))
self.inh.set_trio_genotypes(var)
self.inh.check_heterozygous("X-linked dominant")
self.assertNotEqual(self.inh.log_string, "female x chrom de novo")
def test_check_heterozygous_affected_mother(self):
""" test that check_heterozygous() works correctly for affected mothers
"""
# check that trio with het affected mother is captured
var = TrioGenotypes('X', 100, create_snv('F', "1/0"),
create_snv('F', "1/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
self.inh.mother_affected = True
self.assertEqual(self.inh.check_heterozygous("X-linked dominant"),
"single_variant")
self.assertEqual(
self.inh.log_string,
"x chrom transmitted from aff, other parent non-carrier or aff")
# check that when the other parent is also non-ref, the variant is no
# longer captured, unless the parent is affected
var = TrioGenotypes('X', 100, create_snv('F', "1/0"),
create_snv('F', "1/0"), create_snv('M', "1/1"))
self.inh.set_trio_genotypes(var)
self.assertEqual(self.inh.check_heterozygous("X-linked dominant"),
"nothing")
self.assertEqual(self.inh.log_string,
"variant not compatible with being causal")
self.inh.father_affected = True
self.inh.check_heterozygous("X-linked dominant")
self.assertEqual(
self.inh.log_string,
"x chrom transmitted from aff, other parent non-carrier or aff")
# and check that hemizgygous vars return as "compound_het"
self.assertEqual(self.inh.check_heterozygous("Hemizygous"),
"compound_het")
def setUp(self):
""" define a family and variant, and start the Allosomal class
"""
# generate a test family
child_gender = "F"
mom_aff = "1"
dad_aff = "1"
self.trio = self.create_family(child_gender, mom_aff, dad_aff)
# generate a test variant
child = create_snv(child_gender, "0/1", chrom='X', pos=150,
extra_info='HGNC=TEST;MAX_AF=0.0005')
mom = create_snv("F", "0/0", chrom='X', pos=150)
dad = create_snv("M", "0/0", chrom='X', pos=150)
self.variants = [TrioGenotypes('X', '150', child, mom, dad)]
self.report = Report(None, None, None)
Info.set_populations(["AFR_AF", "AMR_AF", "ASN_AF", "DDD_AF",
"EAS_AF", "ESP_AF", "EUR_AF", "MAX_AF", "SAS_AF", "UK10K_cohort_AF"])
def setUp(self):
""" define a family and variant, and start the Allosomal class
"""
# generate a test family
child_gender = "F"
mom_aff = "1"
dad_aff = "1"
self.trio = self.create_family(child_gender, mom_aff, dad_aff)
# generate a test variant
child = create_snv(child_gender, "0/1")
mom = create_snv("F", "0/0")
dad = create_snv("M", "0/0")
var = TrioGenotypes(child.get_chrom(), child.get_position(), child, mom, dad)
self.variants = [var]
# make sure we've got known genes data
self.known_gene = {"inh": ["Monoallelic"], "confirmed_status": ["confirmed dd gene"]}
self.inh = Allosomal(self.variants, self.trio, self.known_gene, "1001")
self.inh.is_lof = var.child.is_lof()
def test_check_variant_without_parents_male(self):
""" test that check_variant_without_parents() works correctly for males
"""
var = TrioGenotypes('X', 100, create_snv('M', "1/1"), None, None)
trio = self.create_family('male', '1', '1')
self.inh = Allosomal([var], trio, self.known_gene, "TEST")
self.inh.set_trio_genotypes(var)
# check for X-linked dominant inheritance
self.assertEqual(self.inh.check_variant_without_parents("X-linked dominant"), "single_variant")
# and check for hemizygous inheritance
self.assertEqual(self.inh.check_variant_without_parents("Hemizygous"), "single_variant")
def test_check_variant_without_parents_male(self):
""" test that check_variant_without_parents() works correctly for males
"""
var = TrioGenotypes('X', 100, create_snv('M', "1/1"), None, None)
trio = self.create_family('male', '1', '1')
self.inh = Allosomal([var], trio, self.known_gene, "TEST")
self.inh.set_trio_genotypes(var)
# check for X-linked dominant inheritance
self.assertEqual(
self.inh.check_variant_without_parents("X-linked dominant"),
"single_variant")
# and check for hemizygous inheritance
self.assertEqual(self.inh.check_variant_without_parents("Hemizygous"),
"single_variant")
def test_check_heterozygous_de_novo(self):
""" test that check_heterozygous() works correctly for de novos
"""
# all of these tests are run for female X chrom de novos, since male
# X chrom hets don't exist
var = TrioGenotypes('X', 100, create_snv('F', "1/0"),
create_snv('F', "0/0"), create_snv('M', "0/0"))
self.inh.set_trio_genotypes(var)
# check for X-linked dominant inheritance
self.assertEqual(self.inh.check_heterozygous("X-linked dominant"),
"single_variant")
self.assertEqual(self.inh.log_string, "female x chrom de novo")
# check for biallelic inheritance
self.assertEqual(self.inh.check_heterozygous("Hemizygous"),
"single_variant")
# check for X-linked over dominance
self.assertEqual(
self.inh.check_heterozygous("X-linked over-dominance"),
'single_variant')
# check we raise errors with unknown inheritance modes
with self.assertRaises(ValueError):
self.inh.check_heterozygous("Digenic")
genos = {'0': '0/0', '1': '1/0', '2': '1/1'}
for (child, mom, dad) in ["102", "110", "112", "122"]:
var = TrioGenotypes('X', 100, create_snv('F', genos[child]),
create_snv('F', genos[mom]),
create_snv('M', genos[dad]))
self.inh.set_trio_genotypes(var)
self.inh.check_heterozygous("X-linked dominant")
self.assertNotEqual(self.inh.log_string, "female x chrom de novo")
