def setUp(self):
""" create a default ClinicalFilter object to test
"""
class opts:
ped = None
child, mother, father = None, None, None
gender = None
mom_aff, dad_aff = None, None
regions = None
genes, genes_date = None, None
alternate_ids = None
output, export_vcf = None, None
loglevel = "debug"
debug_chrom, debug_pos = None, None
pp_filter = 0.9
self.finder = ClinicalFilter(opts)
class TestClinicalFilterPy(unittest.TestCase):
""" test the ClinicalFilter class
"""
def setUp(self):
""" create a default ClinicalFilter object to test
"""
class opts:
ped = None
child, mother, father = None, None, None
gender = None
mom_aff, dad_aff = None, None
regions = None
genes, genes_date = None, None
alternate_ids = None
output, export_vcf = None, None
loglevel = "debug"
debug_chrom, debug_pos = None, None
pp_filter = 0.9
self.finder = ClinicalFilter(opts)
def create_snv(self, sex, genotype, cq="missense_variant", hgnc="TEST", chrom="1"):
""" create a default variant
"""
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={0};CQ={1};DENOVO-SNP;PP_DNM=0.99".format(hgnc, cq)
keys = "GT:DP:TEAM29_FILTER:PP_DNM"
values = genotype + ":50:PASS:0.99"
var.add_info(info)
var.add_format(keys, values)
var.set_gender(sex)
var.set_genotype()
return var
def create_trio_variant(self, child_gender, cq, hgnc, chrom="1"):
""" create a default TrioGenotypes variant
"""
# generate a test variant
child_var = self.create_snv(child_gender, "0/1", cq, hgnc, chrom)
mom_var = self.create_snv("F", "0/0", cq, hgnc, chrom)
dad_var = self.create_snv("M", "0/0", cq, hgnc, chrom)
var = TrioGenotypes(child_var)
var.add_mother_variant(mom_var)
var.add_father_variant(dad_var)
return var
def test_create_gene_dict(self):
""" test that create_gene_dict works correctly
"""
# create variants that share genes, or not
snv1 = self.create_trio_variant("F", "missense_variant|missense_variant", "TEST1|TEST2")
snv2 = self.create_trio_variant("F", "missense_variant", "TEST1")
snv3 = self.create_trio_variant("F", "missense_variant", "OTHER1")
# the variants that share a gene should be grouped in lists indexed by
# the gene key
self.assertEqual(self.finder.create_gene_dict([snv1, snv2, snv3]),
{"TEST1": [snv1, snv2], "TEST2": [snv1], "OTHER1": [snv3]})
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.
self.finder.family = Family("famID")
self.finder.family.add_child("child_id", "/vcf/path", "2", "F")
self.finder.family.add_father("dad_id", "/vcf/path", "1", "M")
self.finder.family.add_mother("mom_id", "/vcf/path", "1", "F")
self.finder.family.set_child()
# create variants that cover various scenarios
snv1 = self.create_trio_variant("F", "missense_variant|missense_variant", "TEST1|TEST2")
snv2 = self.create_trio_variant("F", "missense_variant|synonymous_variant", "OTHER1|OTHER2")
snv3 = self.create_trio_variant("F", "missense_variant", "")
snv4 = self.create_trio_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"),
[(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"), [])
# 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"), [])
# check that intergenic variants (which lack HGNC symbols) do not pass
self.assertEqual(self.finder.find_variants([snv3], None), [])
# check that a variant on chrX passes through the allosomal instance
self.assertEqual(self.finder.find_variants([snv4], "TESTX"),
[(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(self.finder.find_variants([snv1], "TEST2"),
[(snv1, ["single_variant"], ["Monoallelic"], ["TEST2"])])
# but variants without gene symbols still are excluded
self.assertEqual(self.finder.find_variants([snv3], None), [])
def test_exclude_duplicates(self):
""" test that exclude duplicates works correctly
"""
# create a variant that is within two genes
snv1 = self.create_trio_variant("F", "missense_variant|missense_variant", "TEST1|TEST2")
# two variants that lie in different genes on different chromosomes
# should not be merged
snv2 = self.create_trio_variant("F", "missense_variant", "OTHER1", chrom="2")
variants = [(snv1, ["single_variant"], ["Monoallelic"], ["TEST1"]),
((snv2, ["single_variant"], ["Monoallelic"], ["OTHER1"]))]
self.assertEqual(sorted(self.finder.exclude_duplicates(variants)), sorted(variants))
# create a list of variant tuples that passed filtering for two
# different gene symbols
variants = [(snv1, ["single_variant"], ["Monoallelic"], ["TEST1"]),
((snv1, ["compound_het"], ["Biallelic"], ["TEST1"])),
((snv1, ["compound_het"], ["Biallelic"], ["TEST1"]))]
self.assertEqual(self.finder.exclude_duplicates(variants),
[(snv1, ["single_variant", "compound_het"], ["Monoallelic", "Biallelic"], ["TEST1"])])
# create a list of variant tuples that passed filtering for two
# different gene symbols
variants = [(snv1, ["single_variant"], ["Monoallelic"], ["TEST1"]),
((snv1, ["single_variant"], ["Monoallelic"], ["TEST2"]))]
# the same variant passing for two gene symbols should be collapsed
# into a single entry, where the entry contains a list ofall the gene
# symbols
self.assertEqual(self.finder.exclude_duplicates(variants),
[(snv1, ["single_variant"], ["Monoallelic"], ["TEST1", "TEST2"])])