def test_load_trio(self):
''' test that load_trio() works correctly
'''
def make_vcf(person):
# make a VCF, where one line would pass the default filtering
vcf = make_vcf_header()
vcf.append(make_vcf_line(pos=1, extra='HGNC=TEST;MAX_AF=0.0001'))
vcf.append(make_vcf_line(pos=2, extra='HGNC=ATRX;MAX_AF=0.0001'))
path = os.path.join(self.temp_dir, "{}.vcf.gz".format(person))
self.write_gzipped_vcf(path, vcf)
return path
child_path = make_vcf('child')
mother_path = make_vcf('mother')
father_path = make_vcf('father')
family = Family('fam_id')
family.add_child('sample', 'mother_id', 'father_id', 'female', '2', child_path)
family.add_mother('mother_id', '0', '0', 'female', '1', mother_path)
family.add_father('father_id', '0', '0', 'male', '1', father_path)
family.set_child()
# define the parameters and values for the SNV class
args = {'chrom': "1", 'position': 2, 'id': ".", 'ref': "G", 'alts': "T",
'filter': "PASS", 'info': "CQ=missense_variant;HGNC=ATRX;MAX_AF=0.0001",
'format': "DP:GT", 'sample': "50:0/1", 'gender': "female",
'mnv_code': None}
dad_args = copy.deepcopy(args)
dad_args['gender'] = 'male'
self.assertEqual(self.vcf_loader.load_trio(family),
[TrioGenotypes(chrom="1", pos=2, child=SNV(**args),
mother=SNV(**args), father=SNV(**dad_args)) ])
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 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 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 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 test_load_trio(self):
''' test that load_trio() works correctly
'''
def make_vcf(person):
# make a VCF, where one line would pass the default filtering
vcf = make_vcf_header()
vcf.append(make_vcf_line(pos=1, extra='HGNC=TEST;MAX_AF=0.0001'))
vcf.append(make_vcf_line(pos=2, extra='HGNC=ATRX;MAX_AF=0.0001'))
path = os.path.join(self.temp_dir, "{}.vcf.gz".format(person))
write_gzipped_vcf(path, vcf)
return path
child_path = make_vcf('child')
mother_path = make_vcf('mother')
father_path = make_vcf('father')
family = Family('fam_id')
family.add_child('sample', 'mother_id', 'father_id', 'female', '2',
child_path)
family.add_mother('mother_id', '0', '0', 'female', '1', mother_path)
family.add_father('father_id', '0', '0', 'male', '1', father_path)
family.set_child()
sum_x_lr2_proband = 0
# define the parameters and values for the SNV class
args = {
'chrom': "1",
'position': 2,
'id': ".",
'ref': "G",
'alts': "T",
'filter': "PASS",
'info': "CQ=missense_variant;HGNC=ATRX;MAX_AF=0.0001",
'format': "DP:GT:AD",
'sample': "50:0/1:10,10",
'gender': "female",
'mnv_code': None,
'qual': '1000'
}
dad_args = copy.deepcopy(args)
dad_args['gender'] = 'male'
self.assertEqual(load_trio(family, sum_x_lr2_proband), [
TrioGenotypes(chrom="1",
pos=2,
child=SNV(**args),
mother=SNV(**args),
father=SNV(**dad_args))
])
def test_get_vcf_provenance(self):
""" test that get_vcf_provenance() works correctly
"""
path = os.path.join(self.temp_dir, "temp.vcf")
gz_path = os.path.join(self.temp_dir, "temp.vcf.gz")
date_path = os.path.join(self.temp_dir, "temp.process.2014-02-20.vcf")
family = Family('famid')
family.add_child('child_id', 'mother', 'father', 'f', '2', path)
family.add_mother('mom_id', '0', '0', 'female', '1', gz_path)
family.add_father('dad_id', '0', '0', 'male', '1', date_path)
family.set_child()
vcf = make_minimal_vcf()
vcf_string = "".join(vcf)
if IS_PYTHON3:
vcf_string = vcf_string.encode("utf-8")
ungzipped_hash = hashlib.sha1(vcf_string).hexdigest()
header = vcf[:4]
write_temp_vcf(path, vcf)
# check that the file defs return correctly
(checksum, basename, date) = get_vcf_provenance(family.child)
self.assertEqual(checksum, ungzipped_hash)
self.assertEqual(basename, "temp.vcf")
self.assertEqual(date, "2014-01-01")
# now write a gzip file, and check that we get the correct hash
write_gzipped_vcf(gz_path, vcf)
handle = open(gz_path, "rb")
gzipped_hash = hashlib.sha1(handle.read()).hexdigest()
handle.close()
(checksum, basename, date) = get_vcf_provenance(family.mother)
self.assertEqual(checksum, gzipped_hash)
# check that when a fileDate isn't available in the VCF, we can pick
# the date from the path
vcf.pop(1)
write_temp_vcf(date_path, vcf)
(checksum, basename, date) = get_vcf_provenance(family.father)
self.assertEqual(date, "2014-02-20")
# and check we get null values if the family member is not present
family.father = None
provenance = get_vcf_provenance(family.father)
self.assertEqual(provenance, ('NA', 'NA', 'NA'))
def test_find_variants(self):
""" test that find_variants() works correctly
"""
# define the trio, so that we can know whether the parents are affected.
# The child also needs to be included and set, so that we can get the
# child ID for logging purposes.
family = Family("famID")
family.add_child("child_id", 'dad_id', 'mom_id', 'f', '2', "/vcf/path")
family.add_father("dad_id", '0', '0', 'm', '1', "/vcf/path")
family.add_mother("mom_id", '0', '0', 'f', '1', "/vcf/path")
family.set_child()
# create variants that cover various scenarios
snv1 = create_variant("F", "missense_variant|missense_variant", "TEST1|TEST2")
snv2 = create_variant("F", "missense_variant|synonymous_variant", "OTHER1|OTHER2")
snv3 = create_variant("F", "missense_variant", "")
snv4 = create_variant("F", "missense_variant", "TESTX", chrom="X")
self.finder.known_genes = {"TEST1": {"inh": ["Monoallelic"]},
"OTHER1": {"inh": ["Monoallelic"]},
"OTHER2": {"inh": ["Monoallelic"]},
"TESTX": {"inh": ["X-linked dominant"]}}
# check the simplest case, a variant in a known gene
self.assertEqual(self.finder.find_variants([snv1], "TEST1", family),
[(snv1, ["single_variant"], ["Monoallelic"], ["TEST1"])])
# check that a gene not in a known gene does not pass
self.assertEqual(self.finder.find_variants([snv1], "TEST2", family), [])
# check a variant where the gene is known, but the consequence for that
# gene is not functional, does not pass
self.assertEqual(self.finder.find_variants([snv2], "OTHER2", family), [])
# check that intergenic variants (which lack HGNC symbols) do not pass
self.assertEqual(self.finder.find_variants([snv3], None, family), [])
# check that a variant on chrX passes through the allosomal instance
self.assertEqual(self.finder.find_variants([snv4], "TESTX", family),
[(snv4, ["single_variant"], ["X-linked dominant"], ["TESTX"])])
# remove the known genes, so that the variants in unknown genes pass
self.finder.known_genes = None
self.assertEqual(sorted(self.finder.find_variants([snv1], "TEST2", family)),
[(snv1, ["single_variant"], ["Monoallelic"], ["TEST2"]),
(snv1, ["single_variant"], ["Mosaic"], ["TEST2"])])
# but variants without gene symbols still are excluded
self.assertEqual(self.finder.find_variants([snv3], None, family), [])
def test_get_vcf_provenance(self):
""" test that get_vcf_provenance() works correctly
"""
path = os.path.join(self.temp_dir, "temp.vcf")
gz_path = os.path.join(self.temp_dir, "temp.vcf.gz")
date_path = os.path.join(self.temp_dir, "temp.process.2014-02-20.vcf")
family = Family('famid')
family.add_child('child_id', 'mother', 'father', 'f', '2', path)
family.add_mother('mom_id', '0', '0', 'female', '1', gz_path)
family.add_father('dad_id', '0', '0', 'male', '1', date_path)
family.set_child()
vcf = make_minimal_vcf()
vcf_string = "".join(vcf)
if IS_PYTHON3:
vcf_string = vcf_string.encode("utf-8")
ungzipped_hash = hashlib.sha1(vcf_string).hexdigest()
header = vcf[:4]
write_temp_vcf(path, vcf)
# check that the file defs return correctly
(checksum, basename, date) = get_vcf_provenance(family.child)
self.assertEqual(checksum, ungzipped_hash)
self.assertEqual(basename, "temp.vcf")
self.assertEqual(date, "2014-01-01")
# now write a gzip file, and check that we get the correct hash
write_gzipped_vcf(gz_path, vcf)
handle = open(gz_path, "rb")
gzipped_hash = hashlib.sha1(handle.read()).hexdigest()
handle.close()
(checksum, basename, date) = get_vcf_provenance(family.mother)
self.assertEqual(checksum, gzipped_hash)
# check that when a fileDate isn't available in the VCF, we can pick
# the date from the path
vcf.pop(1)
write_temp_vcf(date_path, vcf)
(checksum, basename, date) = get_vcf_provenance(family.father)
self.assertEqual(date, "2014-02-20")
# and check we get null values if the family member is not present
family.father = None
provenance = get_vcf_provenance(family.father)
self.assertEqual(provenance, ('NA', 'NA', 'NA'))
def test_is_compound_pair_proband_only(self):
""" check that is_compound_pair() includes proband-only pairs
"""
fam = Family("test")
fam.add_child("child", 'dad_id', 'mom_id', 'F', '2', "child_vcf")
fam.set_child()
# set some variants, so we can alter them later
var1 = self.create_variant(chrom="1", position="150", sex="F", cq="stop_gained")
var2 = self.create_variant(chrom="1", position="160", sex="F", cq="stop_gained")
inh = Autosomal([var1, var2], fam, self.known_gene, "TEST")
# check that a proband-only passes, regardless of the parental genotypes
self.assertTrue(inh.is_compound_pair(var1, var2))
def setUp(self):
""" define a default VcfInfo object
"""
family = Family("FamID")
family.add_child("child_id", "/child/path", "2", "M")
family.add_mother("mom_id", "/mother/path", "1", "F")
family.add_father("dad_id", "/father/path", "2", "M")
family.set_child()
variants = []
snv = self.create_var("1", True)
cnv = self.create_var("1", False)
variants.append((snv, ["single_variant"], ["Monoallelic"], ["ATRX"]))
variants.append((cnv, ["single_variant"], ["Monoallelic"], ["ATRX"]))
self.post_filter = PostInheritanceFilter(variants, family)
def setUp(self):
""" define a default variant object
"""
Info.populations = ['AFR_AF']
family = Family('test')
family.add_child('child', 'mother', 'father', 'male', '2', 'child_vcf')
family.add_mother('mother', '0', '0', 'female', '1', 'mother_vcf')
family.add_father('father', '0', '0', 'male', '2', 'father_vcf')
family.set_child()
self.variants = []
snv = self.create_var("1", True)
cnv = self.create_var("1", False)
self.variants.append((snv, ["single_variant"], ["Monoallelic"], ["ATRX"]))
self.variants.append((cnv, ["single_variant"], ["Monoallelic"], ["ATRX"]))
self.post_filter = PostInheritanceFilter(family)
def test_is_compound_pair_proband_only(self):
""" check that is_compound_pair() includes proband-only pairs
"""
fam = Family("test")
fam.add_child("child", 'dad_id', 'mom_id', 'F', '2', "child_vcf")
fam.set_child()
# set some variants, so we can alter them later
var1 = self.create_variant(chrom="1",
position="150",
sex="F",
cq="stop_gained")
var2 = self.create_variant(chrom="1",
position="160",
sex="F",
cq="stop_gained")
inh = Autosomal([var1, var2], fam, self.known_gene, "TEST")
# check that a proband-only passes, regardless of the parental genotypes
self.assertTrue(inh.is_compound_pair(var1, var2))
def setUp(self):
""" define a default variant object
"""
Info.populations = ['AFR_AF']
family = Family('test')
family.add_child('child', 'mother', 'father', 'male', '2', 'child_vcf')
family.add_mother('mother', '0', '0', 'female', '1', 'mother_vcf')
family.add_father('father', '0', '0', 'male', '2', 'father_vcf')
family.set_child()
self.variants = []
snv = self.create_var("1", True)
cnv = self.create_var("1", False)
self.variants.append(
(snv, ["single_variant"], ["Monoallelic"], ["ATRX"]))
self.variants.append(
(cnv, ["single_variant"], ["Monoallelic"], ["ATRX"]))
self.post_filter = PostInheritanceFilter(family)
class TestFamily(unittest.TestCase):
"""
"""
def setUp(self):
""" define a default Person object
"""
ID = "fam_ID"
self.family = Family(ID)
def test__iter__(self):
''' test that __iter__() works correctly
'''
family_id, person_id, mom_id, dad_id = 'fam_ID', 'child', 'dad', 'mom',
path, status, sex = 'child.vcf', '2', 'M'
child = Person(family_id, person_id, dad_id, mom_id, sex, status, path)
self.family.add_child(person_id, dad_id, mom_id, sex, status, path)
self.family.set_child()
# check the Family iterates by getting a list of the Family object
members = list(self.family)
self.assertEqual(members, [child, None, None])
def test_add_father(self):
""" test that add_father() works correctly
"""
person_id = "parent_ID"
path = "/home/parent.vcf"
status = "1"
sex = "1"
dad_id = "0"
mom_id = "0"
# check that adding a male father doesn't raise an error
self.family.add_father(person_id, dad_id, mom_id, sex, status, path)
# check that adding a father for a second time is fine, but adding
# a different father raises an error
self.family.add_father(person_id, dad_id, mom_id, sex, status, path)
with self.assertRaises(ValueError):
self.family.add_father("different_ID", dad_id, mom_id, sex, status,
path)
# check that adding a female father raises an error
self.setUp()
sex = "2"
with self.assertRaises(ValueError):
self.family.add_father(person_id, dad_id, mom_id, sex, status,
path)
def test_add_mother(self):
""" test that add_mother() works correctly
"""
person_id = "parent_ID"
path = "/home/parent.vcf"
status = "1"
sex = "2"
dad_id = "0"
mom_id = "0"
# check that adding a female mother doesn't raise an error
self.family.add_mother(person_id, dad_id, mom_id, sex, status, path)
# check that adding a mother for a second time is fine, but adding
# a different mother raises an error
self.family.add_mother(person_id, dad_id, mom_id, sex, status, path)
with self.assertRaises(ValueError):
self.family.add_mother("different_ID", dad_id, mom_id, sex, status,
path)
# check that adding a male mother raises an error
self.setUp()
sex = "1"
with self.assertRaises(ValueError):
self.family.add_mother(person_id, dad_id, mom_id, sex, status,
path)
def test_add_child(self):
""" check that add_child() works correctly
"""
# check that we can add one child
self.family.add_child("child1", 'dad', 'mom', 'male', '2',
"/home/child1.vcf")
self.assertEqual(len(self.family.children), 1)
# check that adding multiple children works correctly
self.family.add_child("child2", 'dad', 'mom', 'female', '2',
"/home/child2.vcf")
self.family.add_child("child3", 'dad', 'mom', 'male', '2',
"/home/child3.vcf")
self.assertEqual(len(self.family.children), 3)
def test_set_child(self):
""" test that set_child() works correctly
"""
# add one child
self.family.add_child("child1", 'dad', 'mom', 'male', '2',
"/home/child1.vcf")
# check that the child can be set correctly
self.family.set_child()
self.assertEqual(self.family.child, self.family.children[0])
# add more children
self.family.add_child("child2", 'dad', 'mom', 'male', '2',
"/home/child2.vcf")
self.family.add_child("child3", 'dad', 'mom', 'female', '2',
"/home/child3.vcf")
# check that the child can be set correctly with multiple children
self.family.set_child()
self.assertIn(self.family.child, self.family.children)
def test_set_child_examined(self):
""" test that set_child_examined() works correctly
"""
# add one child
self.family.add_child("child1", 'dad', 'mom', 'male', '2',
"/home/child1.vcf")
# check that the child can be set correctly, and can be set as having
# been examined
self.family.set_child()
self.family.set_child_examined()
self.assertTrue(self.family.children[0].is_analysed())
self.assertIsNone(self.family.child)
# add another child, and check that when we set the child, we now pick
# up this child since the other one has previously been examined
self.family.add_child("child2", 'dad', 'mom', 'female', '2',
"/home/child2.vcf")
self.family.set_child()
self.assertEqual(self.family.child, self.family.children[1])
# make sure that set_child_examined() doesn't default to None if we
# have children left to analyse
self.family.add_child("child3", 'dad', 'mom', 'female', '2',
"/home/child3.vcf")
self.family.set_child()
self.family.set_child_examined()
self.assertIsNotNone(self.family.child)
# and set child = None once we have analysed all the children
self.family.set_child()
self.family.set_child_examined()
self.assertIsNone(self.family.child)
def test_find_variants(self):
""" test that find_variants() works correctly
"""
# define the trio, so that we can know whether the parents are affected.
# The child also needs to be included and set, so that we can get the
# child ID for logging purposes.
family = Family("famID")
family.add_child("child_id", 'dad_id', 'mom_id', 'f', '2', "/vcf/path")
family.add_father("dad_id", '0', '0', 'm', '1', "/vcf/path")
family.add_mother("mom_id", '0', '0', 'f', '1', "/vcf/path")
family.set_child()
# create variants that cover various scenarios
snv1 = create_variant("F", "missense_variant|missense_variant",
"TEST1|TEST2")
snv2 = create_variant("F", "missense_variant|synonymous_variant",
"OTHER1|OTHER2")
snv3 = create_variant("F", "missense_variant", "")
snv4 = create_variant("F", "missense_variant", "TESTX", chrom="X")
self.finder.known_genes = {
"TEST1": {
"inh": ["Monoallelic"]
},
"OTHER1": {
"inh": ["Monoallelic"]
},
"OTHER2": {
"inh": ["Monoallelic"]
},
"TESTX": {
"inh": ["X-linked dominant"]
}
}
# check the simplest case, a variant in a known gene
self.assertEqual(
self.finder.find_variants([snv1], "TEST1", family),
[(snv1, ["single_variant"], ["Monoallelic"], ["TEST1"])])
# check that a gene not in a known gene does not pass
self.assertEqual(self.finder.find_variants([snv1], "TEST2", family),
[])
# check a variant where the gene is known, but the consequence for that
# gene is not functional, does not pass
self.assertEqual(self.finder.find_variants([snv2], "OTHER2", family),
[])
# check that intergenic variants (which lack HGNC symbols) do not pass
self.assertEqual(self.finder.find_variants([snv3], None, family), [])
# check that a variant on chrX passes through the allosomal instance
self.assertEqual(
self.finder.find_variants([snv4], "TESTX", family),
[(snv4, ["single_variant"], ["X-linked dominant"], ["TESTX"])])
# remove the known genes, so that the variants in unknown genes pass
self.finder.known_genes = None
self.assertEqual(
sorted(self.finder.find_variants([snv1], "TEST2", family)),
[(snv1, ["single_variant"], ["Monoallelic"], ["TEST2"]),
(snv1, ["single_variant"], ["Mosaic"], ["TEST2"])])
# but variants without gene symbols still are excluded
self.assertEqual(self.finder.find_variants([snv3], None, family), [])
class TestFamily(unittest.TestCase):
"""
"""
def setUp(self):
""" define a default Person object
"""
ID = "fam_ID"
self.family = Family(ID)
def test_add_father(self):
""" test that add_father() works correctly
"""
ID = "parent_ID"
path = "/home/parent.vcf"
affected = "1"
gender = "1"
# check that adding a male father doesn't raise an error
self.family.add_father(ID, path, affected, gender)
# check that adding a father for a second time is fine, but adding
# a different father raises an error
self.family.add_father(ID, path, affected, gender)
with self.assertRaises(ValueError):
self.family.add_father("different_ID", path, affected, gender)
# check that adding a female father raises an error
self.setUp()
gender = "2"
with self.assertRaises(ValueError):
self.family.add_father(ID, path, affected, gender)
def test_add_mother(self):
""" test that add_mother() works correctly
"""
ID = "parent_ID"
path = "/home/parent.vcf"
affected = "1"
gender = "2"
# check that adding a female mother doesn't raise an error
self.family.add_mother(ID, path, affected, gender)
# check that adding a mother for a second time is fine, but adding
# a different mother raises an error
self.family.add_mother(ID, path, affected, gender)
with self.assertRaises(ValueError):
self.family.add_mother("different_ID", path, affected, gender)
# check that adding a male mother raises an error
self.setUp()
gender = "1"
with self.assertRaises(ValueError):
self.family.add_mother(ID, path, affected, gender)
def test_add_child(self):
""" check that add_child() works correctly
"""
# check that we can add one child
self.family.add_child("child1", "/home/child1.vcf", "2", "1")
self.assertEqual(len(self.family.children), 1)
# check that adding multiple children works correctly
self.family.add_child("child2", "/home/child2.vcf", "2", "2")
self.family.add_child("child3", "/home/child3.vcf", "2", "1")
self.assertEqual(len(self.family.children), 3)
def test_set_child(self):
""" test that set_child() works correctly
"""
# add one child
self.family.add_child("child1", "/home/child1.vcf", "2", "1")
# check that the child can be set correctly
self.family.set_child()
self.assertEqual(self.family.child, self.family.children[0])
# add more children
self.family.add_child("child2", "/home/child2.vcf", "2", "1")
self.family.add_child("child3", "/home/child3.vcf", "2", "2")
# check that the child can be set correctly with multiple children
self.family.set_child()
self.assertIn(self.family.child, self.family.children)
def test_set_child_examined(self):
""" test that set_child_examined() works correctly
"""
# add one child
self.family.add_child("child1", "/home/child1.vcf", "2", "1")
# check that the child can be set correctly, and can be set as having
# been examined
self.family.set_child()
self.family.set_child_examined()
self.assertTrue(self.family.children[0].is_analysed())
self.assertIsNone(self.family.child)
# add another child, and check that when we set the child, we now pick
# up this child since the other one has previously been examined
self.family.add_child("child2", "/home/child2.vcf", "2", "2")
self.family.set_child()
self.assertEqual(self.family.child, self.family.children[1])
# make sure that set_child_examined() doesn't default to None if we
# have children left to analyse
self.family.add_child("child3", "/home/child3.vcf", "2", "2")
self.family.set_child()
self.family.set_child_examined()
self.assertIsNotNone(self.family.child)
# and set child = None once we have analysed all the children
self.family.set_child()
self.family.set_child_examined()
self.assertIsNone(self.family.child)