def construct_variant(self, line, gender):
""" constructs a Variant object for a VCF line, specific to the variant type
Args:
line: list of elements of a single sample VCF line:
[chrom, position, snp_id, ref_allele, alt_allele, quality,
filter_value, info, format_keys, format_values]
gender: gender of the individual to whom the variant line belongs
(eg "1" or "M" for male, "2", or "F" for female).
Returns:
returns a Variant object
"""
# CNVs are found by their alt_allele values, as either <DUP>, or <DEL>
if line[4] == "<DUP>" or line[4] == "<DEL>":
var = CNV(line[0], line[1], line[2], line[3], line[4], line[6])
var.add_info(line[7])
# CNVs require the format values for filtering
var.set_gender(gender)
var.add_format(line[8], line[9])
if self.known_genes is not None:
var.fix_gene_IDs()
else:
var = SNV(line[0], line[1], line[2], line[3], line[4], line[6])
var.add_info(line[7])
return var
def construct_variant(self, line, gender):
""" constructs a Variant object for a VCF line, specific to the variant type
Args:
line: list of elements of a single sample VCF line:
[chrom, position, snp_id, ref_allele, alt_allele, quality,
filter_value, info, format_keys, format_values]
gender: gender of the individual to whom the variant line belongs
(eg "1" or "M" for male, "2", or "F" for female).
Returns:
returns a Variant object
"""
# CNVs are found by their alt_allele values, as either <DUP>, or <DEL>
if line[4] == "<DUP>" or line[4] == "<DEL>":
var = CNV(line[0], line[1], line[2], line[3], line[4], line[6])
var.add_info(line[7])
# CNVs require the format values for filtering
var.set_gender(gender)
var.add_format(line[8], line[9])
if self.known_genes is not None:
var.fix_gene_IDs()
else:
var = SNV(line[0], line[1], line[2], line[3], line[4], line[6])
var.add_info(line[7])
return var
def create_cnv(self, gender, inh, chrom, pos, cq=None):
""" create a default variant
"""
snp_id = "."
ref = "A"
alt = "<DEL>"
filt = "PASS"
if cq is None:
cq = "transcript_ablation"
# set up a SNV object, since SNV inherits VcfInfo
var = CNV(chrom, pos, snp_id, ref, alt, filt)
info = "CQ={};HGNC=TEST;HGNC_ALL=TEST;END=16000000;SVLEN=5000".format(
cq)
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_cnv(self, chrom):
pos = "15000000"
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,OR5A1;CQ=missense_variant;CNSOLIDATE;WSCORE=0.5;CALLP=0.000;COMMONFORWARDS=0.000;MEANLR2=0.5;MADL2R=0.02;END=16000000;SVLEN=1000000"
format_keys = "inheritance:DP"
sample_values = "deNovo:50"
var.add_info(info)
var.add_format(format_keys, sample_values)
var.set_gender("F")
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_cnv(self, gender, inh, cifer, 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;CNS=3"
format_keys = "CIFER:INHERITANCE:DP"
sample_values = cifer + ":" + inh + ":50"
var.add_info(info)
var.add_format(format_keys, sample_values)
var.set_gender(gender)
var.set_genotype()
return var
def get_parental_var(self, var, parental_vars, gender, matcher):
""" get the corresponding parental variant to a childs variant, or
create a default variant with reference genotype.
Args:
var: childs var, as Variant object
parental_vars: list of parental variants
gender: gender of the parent
matcher: cnv matcher for parent
Returns:
returns a Variant object, matched to the proband's variant
"""
key = var.get_key()
# if the variant is a CNV, the corresponding variant might not match
# the start site, so we look a variant that overlaps
if isinstance(var, CNV) and matcher.has_match(var):
key = matcher.get_overlap_key(key)
for parental in parental_vars:
if key == parental.get_key():
return parental
# if the childs variant does not exist in the parents VCF, then we
# create a default variant for the parent
if isinstance(var, CNV):
parental = CNV(var.chrom, var.position, var.variant_id,
var.ref_allele, var.alt_allele, var.filter)
else:
parental = SNV(var.chrom, var.position, var.variant_id,
var.ref_allele, var.alt_allele, var.filter)
parental.set_gender(gender)
parental.set_default_genotype()
return parental
def get_parental_var(self, var, parental_vars, gender, matcher):
""" get the corresponding parental variant to a childs variant, or
create a default variant with reference genotype.
Args:
var: childs var, as Variant object
parental_vars: list of parental variants
gender: gender of the parent
matcher: cnv matcher for parent
Returns:
returns a Variant object, matched to the proband's variant
"""
key = var.get_key()
# if the variant is a CNV, the corresponding variant might not match
# the start site, so we look a variant that overlaps
if isinstance(var, CNV) and matcher.has_match(var):
key = matcher.get_overlap_key(key)
for parental in parental_vars:
if key == parental.get_key():
return parental
# if the childs variant does not exist in the parents VCF, then we
# create a default variant for the parent
if isinstance(var, CNV):
parental = CNV(var.chrom, var.position, var.variant_id, var.ref_allele, var.alt_allele, var.filter)
else:
parental = SNV(var.chrom, var.position, var.variant_id, var.ref_allele, var.alt_allele, var.filter)
parental.set_gender(gender)
parental.set_default_genotype()
return parental
class TestVariantCnvPy(unittest.TestCase):
"""
"""
def setUp(self):
""" define a default VcfInfo object
"""
chrom = "1"
pos = "15000000"
snp_id = "."
ref = "A"
alt = "<DUP>"
filt = "PASS"
# set up a SNV object, since SNV inherits VcfInfo
self.var = CNV(chrom, pos, snp_id, ref, alt, filt)
info = "HGNC=TEST;HGNC_ALL=TEST,OR5A1;CQ=missense_variant;CNSOLIDATE;WSCORE=0.5;CALLP=0.000;COMMONFORWARDS=0.000;MEANLR2=0.5;MADL2R=0.02;END=16000000;SVLEN=1000000"
format_keys = "inheritance:DP"
sample_values = "deNovo:50"
self.var.add_info(info)
self.var.add_format(format_keys, sample_values)
self.var.set_gender("F")
def test_set_genotype(self):
""" test that set_genotype() operates correctly
"""
# check that DUPs are set correctly
self.var.alt_allele = "<DUP>"
self.var.set_genotype()
self.assertEqual(self.var.genotype, "DUP")
# check that DELs are set correctly
self.var.alt_allele = "<DEL>"
self.var.set_genotype()
self.assertEqual(self.var.genotype, "DEL")
# check that other genotypes raise an error
self.var.alt_allele = "G"
with self.assertRaises(ValueError):
self.var.set_genotype()
# and check that we raise an error for female Y chrom CNVs
self.var.chrom = "Y"
self.var.set_gender("F")
with self.assertRaises(ValueError):
self.var.set_genotype()
def test_set_genotype_pseudoautosomal(self):
""" test that set_genotype() works correctly in pseudoautosomal regions
"""
pseudoautosomal_region_start = 60002
pseudoautosomal_region_end = 2699520
# set a CNV that lies within a pseudoautosomal region
self.var.chrom = "X"
self.var.position = pseudoautosomal_region_start + 1000
self.var.info["END"] = pseudoautosomal_region_end - 1000
self.var.set_gender("F")
self.var.alt_allele = "<DUP>"
self.var.set_genotype()
self.assertEqual(self.var.genotype, "DUP")
self.assertEqual(self.var.get_inheritance_type(), "autosomal")
def test_get_range(self):
""" test that get_range() operates correctly
"""
# check that range is set correctly under normal function
self.var.position = 1000
self.var.info["END"] = "2000"
self.assertEqual(self.var.get_range(), (1000, 2000))
# check that range is set correctly when no info available
self.var.info = {}
self.assertEqual(self.var.get_range(), (1000, 11000))
def test_fix_gene_IDs(self):
""" test that fix_gene_IDs() works correctly
"""
self.var.known_genes = {"TEST": {"start": 1000, "end": 2000, "chrom": "5"}}
# make a CNV that will overlap with the known gene set
self.var.genes = ["TEST"]
self.var.position = 1000
self.var.info["END"] = "1500"
# check that fixing gene names does not alter anything for a CNV in a
# single known gene
self.var.fix_gene_IDs()
self.assertEqual(self.var.genes, ["TEST"])
# check that fixing gene names does not alter names not in the gene dict
self.var.genes = ["TEST", "TEST2"]
self.var.fix_gene_IDs()
self.assertEqual(self.var.genes, ["TEST", "TEST2"])
# check that fixing gene names drop name of genes where the name is in
# the known genes dict, and the CNV and gene do not overlap
self.var.position = 900
self.var.info["END"] = "950"
self.var.fix_gene_IDs()
self.assertEqual(self.var.genes, [".", "TEST2"])
# check that when we do not have any known genes, the gene names are
# unaltered
self.var.genes = ["TEST", "TEST2"]
self.var.known_genes = None
self.var.fix_gene_IDs()
self.assertEqual(self.var.genes, ["TEST", "TEST2"])
def test_set_gene_from_info_cnv(self):
""" test that set_add_gene_from_info() works correctly
"""
# make sure the known genes are None, otherwise sometimes the values
# from test_variant_info.py unit tests can bleed through. I'm not sure
# why!
self.var.known_genes = None
# check that HGNC takes precedence
self.var.info["HGNC"] = "A"
self.var.info["HGNC_ALL"] = "B"
self.var.set_gene_from_info()
self.assertEqual(self.var.genes, ["A"])
# check that HGNC is used in the absence of HGNC_ALL
del self.var.info["HGNC"]
self.var.set_gene_from_info()
self.assertEqual(self.var.genes, ["B"])
# check that when HGNC and HGNC_ALL are undefined, we can still include
# CNVs overlapping genes through NUMBERGENES > 0.
del self.var.info["HGNC_ALL"]
# first test for NUMBERGENES = 0
self.var.info["NUMBERGENES"] = 0
self.var.set_gene_from_info()
self.assertIsNone(self.var.genes)
# and then make sure we are correct for NUMBERGENES > 0
self.var.info["NUMBERGENES"] = 1
self.var.set_gene_from_info()
self.assertEqual(self.var.genes, ["."])
# finally check for no HGNC, HGNC_ALL, or NUMBERGENES
del self.var.info["NUMBERGENES"]
self.var.set_gene_from_info()
self.assertEqual(self.var.genes, "1:15000000")
def test_get_genes(self):
""" test that get_genes() works correctly
"""
self.var.genes = None
self.assertEqual(self.var.get_genes(), [])
self.var.genes = ["TEST"]
self.assertEqual(self.var.get_genes(), ["TEST"])
self.var.genes = ["TEST1", "TEST2"]
self.assertEqual(self.var.get_genes(), ["TEST1", "TEST2"])
self.var.genes = ["."]
self.assertEqual(self.var.get_genes(), ["."])
def test_fails_y_chrom_female(self):
""" test that passes_filters() works correctly for female Y chrom CNVs
"""
self.var.chrom = "Y"
self.var.set_gender("F")
self.assertFalse(self.var.passes_filters())