class TestAllosomalPy(unittest.TestCase):
""" test the Allosomal class
"""
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_var = self.create_snv(child_gender, "0/1")
mom_var = self.create_snv("F", "0/0")
dad_var = self.create_snv("M", "0/0")
var = TrioGenotypes(child_var)
var.add_mother_variant(mom_var)
var.add_father_variant(dad_var)
self.variants = [var]
# make sure we've got known genes data
self.known_genes = {"TEST": {"inh": ["Monoallelic"], "confirmed_status": ["Confirmed DD Gene"]}}
self.inh = Allosomal(self.variants, self.trio, self.known_genes, "TEST")
self.inh.is_lof = var.child.is_lof()
def create_snv(self, gender, genotype):
""" create a default variant
"""
chrom = "X"
pos = "15000000"
snp_id = "."
ref = "A"
alt = "G"
filt = "PASS"
# set up a SNV object, since SNV inherits VcfInfo
var = SNV(chrom, pos, snp_id, ref, alt, filt)
info = "HGNC=TEST;CQ=missense_variant;random_tag"
format_keys = "GT:DP"
sample_values = genotype + ":50"
var.add_info(info)
var.add_format(format_keys, sample_values)
var.set_gender(gender)
var.set_genotype()
return var
def create_cnv(self, gender, inh, chrom, pos):
""" create a default variant
"""
snp_id = "."
ref = "A"
alt = "<DUP>"
filt = "PASS"
# set up a SNV object, since SNV inherits VcfInfo
var = CNV(chrom, pos, snp_id, ref, alt, filt)
info = "HGNC=TEST;HGNC_ALL=TEST;END=16000000;SVLEN=5000"
format_keys = "INHERITANCE:DP"
sample_values = inh + ":50"
var.add_info(info)
var.add_format(format_keys, sample_values)
var.set_gender(gender)
var.set_genotype()
return var
def create_family(self, child_gender, mom_aff, dad_aff):
""" create a default family, with optional gender and parental statuses
"""
fam = Family("test")
fam.add_child("child", "child_vcf", "2", child_gender)
fam.add_mother("mother", "mother_vcf", mom_aff, "2")
fam.add_father("father", "father_vcf", dad_aff, "1")
fam.set_child()
return fam
def set_trio_genos(self, var, geno):
""" convenience function to set the trio genotypes for a variant
"""
genos = {"0": "0/0", "1": "0/1", "2": "1/1"}
# convert the geno codes to allele codes
child = genos[geno[0]]
mom = genos[geno[1]]
dad = genos[geno[2]]
# set the genotype field for each individual
var.child.format["GT"] = child
var.mother.format["GT"] = mom
var.father.format["GT"] = dad
# and set th genotype for each individual
var.child.set_genotype()
var.mother.set_genotype()
var.father.set_genotype()
# set the trio genotypes for the inheritance object
self.inh.set_trio_genotypes(var)
def test_check_variant_without_parents_female(self):
""" test that check_variant_without_parents() works correctly for female
"""
var = self.variants[0]
var.child.set_gender("F")
self.set_trio_genos(var, "100")
# remove the parents, so it appears the var lacks parental information
self.inh.trio.mother = None
self.inh.trio.father = None
# 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")
self.set_trio_genos(var, "200")
self.assertEqual(self.inh.check_variant_without_parents("X-linked dominant"), "single_variant")
# and check for hemizygous inheritance
self.set_trio_genos(var, "100")
self.assertEqual(self.inh.check_variant_without_parents("Hemizygous"), "hemizygous")
self.set_trio_genos(var, "200")
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 = self.variants[0]
var.child.set_gender("M")
self.set_trio_genos(var, "200")
# remove the parents, so it appears the var lacks parental information
self.inh.trio.mother = None
self.inh.trio.father = None
# 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 = self.variants[0]
self.set_trio_genos(var, "100")
# 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")
with self.assertRaises(ValueError):
self.inh.check_heterozygous("X-linked over-dominance")
for geno in ["102", "110", "112", "122"]:
self.set_trio_genos(var, geno)
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
"""
var = self.variants[0]
# check that trio = 110, with het affected mother is captured
self.set_trio_genos(var, "110")
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
self.set_trio_genos(var, "112")
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 test_check_heterozygous_affected_father(self):
""" test that check_heterozygous() works correctly for affected fathers
"""
var = self.variants[0]
# set the father as non-ref genotype and affected
self.set_trio_genos(var, "102")
# 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
self.set_trio_genos(var, "112")
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_homozygous_male(self):
""" test that check_homozygous() works correctly for males
"""
var = self.variants[0]
self.trio.child.gender = "M"
# check for trio = 200, which is de novo on male X chrom
self.set_trio_genos(var, "200")
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
self.set_trio_genos(var, "210")
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 not pass
self.inh.mother_affected = True
self.assertEqual(self.inh.check_homozygous("X-linked dominant"), "nothing")
self.assertEqual(self.inh.log_string, "variant not compatible with being causal")
# check for trio = 220, with affected mother
self.set_trio_genos(var, "220")
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.set_trio_genos(var, "220")
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 non-standard inheritance modes raise errors
with self.assertRaises(ValueError):
self.inh.check_homozygous("X-linked over-dominance")
def test_check_homozygous_female(self):
""" test that check_homozygous() works correctly for females
"""
var = self.variants[0]
# check for trio = 200, which is non-mendelian
self.set_trio_genos(var, "200")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# check for trio = 210, which is non-mendelian
self.set_trio_genos(var, "210")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# check for trio = 202, which is non-mendelian
self.set_trio_genos(var, "202")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# and check for trio = 212, without affected parents
self.set_trio_genos(var, "212")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "variant not compatible with being causal")
# and check for trio = 212, with affected father
self.set_trio_genos(var, "212")
self.inh.father_affected = True
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "single_variant")
self.assertEqual(self.inh.log_string, "testing")
# and check for trio = 212, with affected mother
self.set_trio_genos(var, "212")
self.inh.mother_affected = True
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "single_variant")
self.assertEqual(self.inh.log_string, "testing")
# and check for trio = 222, with affected mother
self.set_trio_genos(var, "222")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "single_variant")
self.assertEqual(self.inh.log_string, "testing")
# and check for trio = 222, with affected mother
self.set_trio_genos(var, "222")
self.inh.mother_affected = False
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "variant not compatible with being causal")
def test_check_homozygous_with_cnv(self):
""" test that check_homozygous() works correctly for variant lists with CNVs
"""
# generate a test variant
chrom = "X"
position = "60000"
child_var = self.create_cnv("F", "unknown", chrom, position)
mom_var = self.create_cnv("F", "unknown", chrom, position)
dad_var = self.create_cnv("M", "unknown", chrom, position)
cnv_var = TrioGenotypes(child_var)
cnv_var.add_mother_variant(mom_var)
cnv_var.add_father_variant(dad_var)
var = self.variants[0]
# check for trio = 200, which is non-mendelian
self.set_trio_genos(var, "200")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# check when a CNV is in the variants list
self.inh.variants.append(cnv_var)
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "compound_het")
self.assertEqual(self.inh.log_string, "non-mendelian, but CNV might affect call")
class TestAllosomalPy(unittest.TestCase):
""" test the Allosomal class
"""
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 create_family(self, child_gender, mom_aff, dad_aff):
""" create a default family, with optional gender and parental statuses
"""
fam = Family('test')
fam.add_child('child', 'mother', 'father', child_gender, '2', 'child_vcf')
fam.add_mother('mother', '0', '0', 'female', mom_aff, 'mother_vcf')
fam.add_father('father', '0', '0', 'male', dad_aff, 'father_vcf')
fam.set_child()
return fam
def set_trio_genos(self, var, geno):
""" convenience function to set the trio genotypes for a variant
"""
genos = {"0": "0/0", "1": "0/1", "2": "1/1"}
# convert the geno codes to allele codes
child = genos[geno[0]]
mom = genos[geno[1]]
dad = genos[geno[2]]
# set the genotype field for each individual
var.child.format["GT"] = child
var.mother.format["GT"] = mom
var.father.format["GT"] = dad
# and set th genotype for each individual
var.child.set_genotype()
var.mother.set_genotype()
var.father.set_genotype()
# set the trio genotypes for the inheritance object
self.inh.set_trio_genotypes(var)
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_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")
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 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_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_homozygous_female(self):
""" test that check_homozygous() works correctly for females
"""
var = self.variants[0]
# check for trio = 200, which is non-mendelian
self.set_trio_genos(var, "200")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# check for trio = 210, which is non-mendelian
self.set_trio_genos(var, "210")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# check for trio = 202, which is non-mendelian
self.set_trio_genos(var, "202")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# and check for trio = 212, without affected parents
self.set_trio_genos(var, "212")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "variant not compatible with being causal")
# and check for trio = 212, with affected father
self.set_trio_genos(var, "212")
self.inh.father_affected = True
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "single_variant")
self.assertEqual(self.inh.log_string, "testing")
# and check for trio = 212, with affected mother
self.set_trio_genos(var, "212")
self.inh.mother_affected = True
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "single_variant")
self.assertEqual(self.inh.log_string, "testing")
# and check for trio = 222, with affected mother
self.set_trio_genos(var, "222")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "single_variant")
self.assertEqual(self.inh.log_string, "testing")
# and check for trio = 222, with affected mother
self.set_trio_genos(var, "222")
self.inh.mother_affected = False
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "variant not compatible with being causal")
def test_check_homozygous_with_cnv(self):
""" test that check_homozygous() works correctly for variant lists with CNVs
"""
# generate a test variant
chrom = "X"
pos = '160'
child = create_cnv('F', 'unknown', chrom=chrom, pos=pos)
mom = create_cnv('F', 'unknown', chrom=chrom, pos=pos)
dad = create_cnv('F', 'unknown', chrom=chrom, pos=pos)
cnv = TrioGenotypes(chrom, pos, child, mom, dad)
var = self.variants[0]
# check for trio = 200, which is non-mendelian
self.set_trio_genos(var, "200")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# check when a CNV is in the variants list
self.inh.variants.append(cnv)
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "compound_het")
self.assertEqual(self.inh.log_string, "non-mendelian, but CNV might affect call")
class TestAllosomalPy(unittest.TestCase):
""" test the Allosomal class
"""
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 create_family(self, child_gender, mom_aff, dad_aff):
""" create a default family, with optional gender and parental statuses
"""
fam = Family('test')
fam.add_child('child', 'mother', 'father', child_gender, '2',
'child_vcf')
fam.add_mother('mother', '0', '0', 'female', mom_aff, 'mother_vcf')
fam.add_father('father', '0', '0', 'male', dad_aff, 'father_vcf')
fam.set_child()
return fam
def set_trio_genos(self, var, geno):
""" convenience function to set the trio genotypes for a variant
"""
genos = {"0": "0/0", "1": "0/1", "2": "1/1"}
# convert the geno codes to allele codes
child = genos[geno[0]]
mom = genos[geno[1]]
dad = genos[geno[2]]
# set the genotype field for each individual
var.child.format["GT"] = child
var.mother.format["GT"] = mom
var.father.format["GT"] = dad
# and set th genotype for each individual
var.child.set_genotype()
var.mother.set_genotype()
var.father.set_genotype()
# set the trio genotypes for the inheritance object
self.inh.set_trio_genotypes(var)
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_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")
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 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_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_homozygous_female(self):
""" test that check_homozygous() works correctly for females
"""
var = self.variants[0]
# check for trio = 200, which is non-mendelian
self.set_trio_genos(var, "200")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# check for trio = 210, which is non-mendelian
self.set_trio_genos(var, "210")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# check for trio = 202, which is non-mendelian
self.set_trio_genos(var, "202")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# and check for trio = 212, without affected parents
self.set_trio_genos(var, "212")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string,
"variant not compatible with being causal")
# and check for trio = 212, with affected father
self.set_trio_genos(var, "212")
self.inh.father_affected = True
self.assertEqual(self.inh.check_homozygous("Hemizygous"),
"single_variant")
self.assertEqual(self.inh.log_string, "testing")
# and check for trio = 212, with affected mother
self.set_trio_genos(var, "212")
self.inh.mother_affected = True
self.assertEqual(self.inh.check_homozygous("Hemizygous"),
"single_variant")
self.assertEqual(self.inh.log_string, "testing")
# and check for trio = 222, with affected mother
self.set_trio_genos(var, "222")
self.assertEqual(self.inh.check_homozygous("Hemizygous"),
"single_variant")
self.assertEqual(self.inh.log_string, "testing")
# and check for trio = 222, with affected mother
self.set_trio_genos(var, "222")
self.inh.mother_affected = False
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string,
"variant not compatible with being causal")
def test_check_homozygous_with_cnv(self):
""" test that check_homozygous() works correctly for variant lists with CNVs
"""
# generate a test variant
chrom = "X"
pos = '160'
child = create_cnv('F', 'unknown', chrom=chrom, pos=pos)
mom = create_cnv('F', 'unknown', chrom=chrom, pos=pos)
dad = create_cnv('F', 'unknown', chrom=chrom, pos=pos)
cnv = TrioGenotypes(chrom, pos, child, mom, dad)
var = self.variants[0]
# check for trio = 200, which is non-mendelian
self.set_trio_genos(var, "200")
self.assertEqual(self.inh.check_homozygous("Hemizygous"), "nothing")
self.assertEqual(self.inh.log_string, "non-mendelian trio")
# check when a CNV is in the variants list
self.inh.variants.append(cnv)
self.assertEqual(self.inh.check_homozygous("Hemizygous"),
"compound_het")
self.assertEqual(self.inh.log_string,
"non-mendelian, but CNV might affect call")
