def setUp(self):
self._braf_classification = AlterationClassification("BRAF", ["missense_variant"], "ENST00000288602", ["p.Val600Glu"], "BRAF_COMMON")
braf = Gene("BRAF")
braf.set_ID("ENSG00000157764")
self._braf_gene = AlteredGene(braf)
self._braf_alteration1 = Alteration(self._braf_gene, "ENST00000288602", "missense_variant", "p.Val600Glu")
self._braf_gene.add_alteration(self._braf_alteration1)
self._kras_classification = AlterationClassification("KRAS", ["missense_variant"], "ENST00000256078", ["12", "13", "60", "61", "117", "146"], "KRAS_COMMON")
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene = AlteredGene(kras)
self._kras_alteration1 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Ala146Pro")
self._kras_gene.add_alteration(self._kras_alteration1)
# A fake mutation whose position is in the set of KRAS mutations:
self._kras_alteration2 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Lys60Pro")
self._kras_gene.add_alteration(self._kras_alteration2)
# A fake mutation that is *not* in the set of KRAS mutations:
self._kras_alteration3 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Lys1Asn")
self._kras_gene.add_alteration(self._kras_alteration3)
self._pik3r1_range_classification = AlterationClassification("PIK3R1", ["inframe_insertion"], "ENST00000521381", ["340:670"], "TEST")
pik3r1 = Gene("PIK3R1")
pik3r1.set_ID("ENSG00000145675")
self._pik3r1_gene = AlteredGene(pik3r1)
# Dummy alteration; position is important, substitution is not:
self._pik3r1_alteration1 = Alteration(self._pik3r1_gene, "ENST00000521381", "inframe_insertion", "p.Val344Lys")
def setUp(self):
self._extractor = AlterationExtractor()
nras = Gene("NRAS")
nras.set_ID("ENSG00000213281")
self._nras_gene = AlteredGene(nras)
test_alteration1 = Alteration(self._nras_gene, "ENST00000369535", "missense_variant", "p.Gln61His")
self._nras_gene.add_alteration(test_alteration1)
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene = AlteredGene(kras)
test_alteration2 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Ala146Pro")
self._kras_gene.add_alteration(test_alteration2)
test_alteration3 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Lys117Asn")
self._kras_gene.add_alteration(test_alteration3)
pten = Gene("PTEN")
pten.set_ID(None)
self._pten_gene_loh = AlteredGene(pten)
test_alteration4 = Alteration(self._pten_gene_loh, None, "loss_of_heterozygosity", None)
self._pten_gene_loh.add_alteration(test_alteration4)
self._pten_gene_hloss = AlteredGene(pten)
test_alteration5 = Alteration(self._pten_gene_hloss, None, "homozygous_loss", None)
self._pten_gene_hloss.add_alteration(test_alteration5)
def setUp(self):
self._extractor = AlterationExtractor()
nras = Gene("NRAS")
nras.set_ID("ENSG00000213281")
self._nras_gene = AlteredGene(nras)
test_alteration1 = Alteration(self._nras_gene, "ENST00000369535",
"missense_variant", "p.Gln61His")
self._nras_gene.add_alteration(test_alteration1)
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene = AlteredGene(kras)
test_alteration2 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Ala146Pro")
self._kras_gene.add_alteration(test_alteration2)
test_alteration3 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Lys117Asn")
self._kras_gene.add_alteration(test_alteration3)
pten = Gene("PTEN")
pten.set_ID(None)
self._pten_gene_loh = AlteredGene(pten)
test_alteration4 = Alteration(self._pten_gene_loh, None,
"loss_of_heterozygosity", None)
self._pten_gene_loh.add_alteration(test_alteration4)
self._pten_gene_hloss = AlteredGene(pten)
test_alteration5 = Alteration(self._pten_gene_hloss, None,
"homozygous_loss", None)
self._pten_gene_hloss.add_alteration(test_alteration5)
def setUp(self):
braf_classification = AlterationClassification("BRAF",
["missense_variant"],
"ENST00000288602",
["p.Val600Glu"],
"BRAF_COMMON")
kras_classification = AlterationClassification(
"KRAS", ["missense_variant"], "ENST00000256078",
["12", "13", "60", "61", "117", "146"], "KRAS_COMMON")
nras_classification = AlterationClassification("NRAS",
["missense_variant"],
"ENST00000369535",
["12", "13", "61"],
"NRAS_COMMON")
self._symbol2classifications = {
"BRAF": [braf_classification],
"KRAS": [kras_classification],
"NRAS": [nras_classification]
}
braf = Gene("BRAF")
braf.set_ID("ENSG00000157764")
self._braf_gene_single_mutation = AlteredGene(braf)
self._braf_alteration3 = Alteration(self._braf_gene_single_mutation,
"ENST00000288602",
"missense_variant", "p.Val600Glu")
self._braf_gene_single_mutation.add_alteration(self._braf_alteration3)
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene_multiple_mutations = AlteredGene(kras)
self._kras_alteration1 = Alteration(self._kras_gene_multiple_mutations,
"ENST00000256078",
"missense_variant", "p.Ala146Pro")
self._kras_gene_multiple_mutations.add_alteration(
self._kras_alteration1)
# Position only specified:
self._kras_alteration2 = Alteration(self._kras_gene_multiple_mutations,
"ENST00000256078",
"missense_variant", "p.Lys117Asn")
self._kras_gene_multiple_mutations.add_alteration(
self._kras_alteration2)
# A fake mutation that is *not* in the set of KRAS mutations:
self._kras_alteration3 = Alteration(self._kras_gene_multiple_mutations,
"ENST00000256078",
"missense_variant", "p.Lys1Asn")
self._kras_gene_multiple_mutations.add_alteration(
self._kras_alteration3)
def setUp(self):
self._braf_classification = AlterationClassification(
"BRAF", ["missense_variant"], "ENST00000288602", ["p.Val600Glu"],
"BRAF_COMMON")
braf = Gene("BRAF")
braf.set_ID("ENSG00000157764")
self._braf_gene = AlteredGene(braf)
self._braf_alteration1 = Alteration(self._braf_gene, "ENST00000288602",
"missense_variant", "p.Val600Glu")
self._braf_gene.add_alteration(self._braf_alteration1)
self._kras_classification = AlterationClassification(
"KRAS", ["missense_variant"], "ENST00000256078",
["12", "13", "60", "61", "117", "146"], "KRAS_COMMON")
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene = AlteredGene(kras)
self._kras_alteration1 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Ala146Pro")
self._kras_gene.add_alteration(self._kras_alteration1)
# A fake mutation whose position is in the set of KRAS mutations:
self._kras_alteration2 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Lys60Pro")
self._kras_gene.add_alteration(self._kras_alteration2)
# A fake mutation that is *not* in the set of KRAS mutations:
self._kras_alteration3 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Lys1Asn")
self._kras_gene.add_alteration(self._kras_alteration3)
self._pik3r1_range_classification = AlterationClassification(
"PIK3R1", ["inframe_insertion"], "ENST00000521381", ["340:670"],
"TEST")
pik3r1 = Gene("PIK3R1")
pik3r1.set_ID("ENSG00000145675")
self._pik3r1_gene = AlteredGene(pik3r1)
# Dummy alteration; position is important, substitution is not:
self._pik3r1_alteration1 = Alteration(self._pik3r1_gene,
"ENST00000521381",
"inframe_insertion",
"p.Val344Lys")
def setUp(self):
braf_classification = AlterationClassification("BRAF", ["missense_variant"], "ENST00000288602", ["p.Val600Glu"], "BRAF_COMMON")
kras_classification = AlterationClassification("KRAS", ["missense_variant"], "ENST00000256078", ["12", "13", "60", "61", "117", "146"], "KRAS_COMMON")
nras_classification = AlterationClassification("NRAS", ["missense_variant"], "ENST00000369535", ["12", "13", "61"], "NRAS_COMMON")
self._symbol2classifications = {"BRAF": [braf_classification], "KRAS": [kras_classification], "NRAS": [nras_classification]}
braf = Gene("BRAF")
braf.set_ID("ENSG00000157764")
self._braf_gene_single_mutation = AlteredGene(braf)
self._braf_alteration3 = Alteration(self._braf_gene_single_mutation, "ENST00000288602", "missense_variant", "p.Val600Glu")
self._braf_gene_single_mutation.add_alteration(self._braf_alteration3)
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene_multiple_mutations = AlteredGene(kras)
self._kras_alteration1 = Alteration(self._kras_gene_multiple_mutations, "ENST00000256078", "missense_variant", "p.Ala146Pro")
self._kras_gene_multiple_mutations.add_alteration(self._kras_alteration1)
# Position only specified:
self._kras_alteration2 = Alteration(self._kras_gene_multiple_mutations, "ENST00000256078", "missense_variant", "p.Lys117Asn")
self._kras_gene_multiple_mutations.add_alteration(self._kras_alteration2)
# A fake mutation that is *not* in the set of KRAS mutations:
self._kras_alteration3 = Alteration(self._kras_gene_multiple_mutations, "ENST00000256078", "missense_variant", "p.Lys1Asn")
self._kras_gene_multiple_mutations.add_alteration(self._kras_alteration3)
class TestAlterationExtractor(unittest.TestCase):
_extractor = None
def setUp(self):
self._extractor = AlterationExtractor()
nras = Gene("NRAS")
nras.set_ID("ENSG00000213281")
self._nras_gene = AlteredGene(nras)
test_alteration1 = Alteration(self._nras_gene, "ENST00000369535",
"missense_variant", "p.Gln61His")
self._nras_gene.add_alteration(test_alteration1)
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene = AlteredGene(kras)
test_alteration2 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Ala146Pro")
self._kras_gene.add_alteration(test_alteration2)
test_alteration3 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Lys117Asn")
self._kras_gene.add_alteration(test_alteration3)
pten = Gene("PTEN")
pten.set_ID(None)
self._pten_gene_loh = AlteredGene(pten)
test_alteration4 = Alteration(self._pten_gene_loh, None,
"loss_of_heterozygosity", None)
self._pten_gene_loh.add_alteration(test_alteration4)
self._pten_gene_hloss = AlteredGene(pten)
test_alteration5 = Alteration(self._pten_gene_hloss, None,
"homozygous_loss", None)
self._pten_gene_hloss.add_alteration(test_alteration5)
def test_gene(self):
self._extractor.extract_mutations(
open("tests/simple_variant_input.vcf"))
output_dict = self._extractor.to_dict()
self.assertEqual(output_dict["NRAS"].get_gene().get_symbol(), "NRAS")
self.assertEqual(output_dict["NRAS"].get_gene().get_ID(),
self._nras_gene.get_gene().get_ID())
def test_extract_mutations_empty_input(self):
self._extractor.extract_mutations(open("tests/empty_input.vcf"))
output_dict = self._extractor.to_dict()
expected_dict = {}
self.assertDictEqual(output_dict, expected_dict)
def test_extract_mutations_empty_input_without_header(self):
self._extractor.extract_mutations(
open("tests/empty_input_without_header.vcf"))
output_dict = self._extractor.to_dict()
expected_dict = {}
self.assertDictEqual(output_dict, expected_dict)
def test_extract_mutations_multiple_mutations(self):
self._extractor.extract_mutations(
open("tests/multiple_mutations_variant_input.vcf"))
output_dict = self._extractor.to_dict()
expected_dict = {"KRAS": self._kras_gene}
self.assertEqual(len(output_dict.keys()), len(expected_dict.keys()))
self.assertEqual(output_dict["KRAS"].get_gene().get_ID(),
expected_dict["KRAS"].get_gene().get_ID())
def test_extract_mutations_multiple_genes(self):
self._extractor.extract_mutations(
open("tests/multiple_genes_variant_input.vcf"))
output_dict = self._extractor.to_dict()
expected_dict = {"KRAS": self._kras_gene, "NRAS": self._nras_gene}
self.assertEqual(len(output_dict.keys()), len(expected_dict.keys()))
self.assertEqual(output_dict["NRAS"].get_gene().get_ID(),
expected_dict["NRAS"].get_gene().get_ID())
def test_extract_cnvs_gene_no_call(self):
self._extractor.extract_cnvs(open("tests/pten_no_call.json"))
output_dict = self._extractor.to_dict()
# Output dictionary should be empty as there is no call:
self.assertDictEqual(output_dict, {})
def test_extract_cnvs_gene_hom_loss(self):
self._extractor.extract_cnvs(open("tests/pten_hom_loss.json"))
output_dict = self._extractor.to_dict()
# Output dictionary should be empty as there is no call:
self.assertEqual(output_dict["PTEN"].get_gene().get_symbol(), "PTEN")
self.assertEqual(len(output_dict["PTEN"].get_alterations()), 1)
self.assertEqual(
output_dict["PTEN"].get_alterations()[0].get_sequence_ontology(),
"homozygous_loss")
def test_extract_cnvs_gene_het_loss(self):
self._extractor.extract_cnvs(open("tests/pten_het_loss.json"))
output_dict = self._extractor.to_dict()
# Output dictionary should be empty as there is no call:
self.assertEqual(output_dict["PTEN"].get_gene().get_symbol(), "PTEN")
self.assertEqual(output_dict["PTEN"].get_gene().get_ID(),
"ENSG00000171862")
self.assertEqual(len(output_dict["PTEN"].get_alterations()), 1)
self.assertEqual(
output_dict["PTEN"].get_alterations()[0].get_sequence_ontology(),
"loss_of_heterozygosity")
self.assertEqual(
output_dict["PTEN"].get_alterations()[0].get_transcript_ID(),
"ENST00000371953")
def test_extract_cnvs_invalid_inputs1(self):
self.assertRaises(ValueError, self._extractor.extract_cnvs,
open("tests/pten_invalid_call.json"))
def setUp(self):
igf2_classification = AlterationClassification("IGF2",
["amplification"], None,
[], "ALASCCA_CLASS_B_1")
pten_classification_b_2 = AlterationClassification(
"PTEN", [
"start_lost", "stop_gained", "frameshift_variant",
"splice_acceptor_variant", "splice_donor_variant",
"loss_of_heterozygosity"
], "ENST00000371953", [], "ALASCCA_CLASS_B_2")
pten_classification_b_1 = AlterationClassification(
"PTEN", ["homozygous_loss"], "ENST00000371953", [],
"ALASCCA_CLASS_B_1")
pten_classification_b_1_missense = AlterationClassification(
"PTEN", ["missense_variant"], "ENST00000371953",
["p.Cys124Ser", "p.Gly129Glu", "p.Arg130Gly", "p.Arg130Gln"],
"ALASCCA_CLASS_B_1")
pik3r1_classification_b_1 = AlterationClassification(
"PIK3R1", [
"frameshift_variant", "inframe_insertion", "inframe_deletion",
"stop_gained", "splice_acceptor_variant",
"splice_donor_variant"
], "ENST00000521381", ["340:670"], "ALASCCA_CLASS_B_1")
pik3r1_classification_b_1_missense = AlterationClassification(
"PIK3R1", ["missense_variant"], "ENST00000521381", [
"376", "379", "452", "464", "503", "560", "564", "567", "573",
"642"
], "ALASCCA_CLASS_B_1")
pik3ca_classification_b_1 = AlterationClassification(
"PIK3CA", ["missense_variant"], "ENST00000263967", [
"38", "81", "88", "106", "111", "118", "344", "345", "378",
"420", "453", "726"
], "ALASCCA_CLASS_B_1")
pik3ca_classification_a = AlterationClassification(
"PIK3CA", ["missense_variant"], "ENST00000263967",
["542", "545", "546", "1021", "1043", "1044", "1047"],
"ALASCCA_CLASS_A")
self._symbol2classifications = {
"IGF2": [igf2_classification],
"PTEN": [
pten_classification_b_2, pten_classification_b_1,
pten_classification_b_1_missense
],
"PIK3R1":
[pik3r1_classification_b_1, pik3r1_classification_b_1_missense],
"PIK3CA": [pik3ca_classification_b_1, pik3ca_classification_a]
}
pten = Gene("PTEN")
pten.set_ID("ENSG00000171862")
self._pten_gene_single_mutation = AlteredGene(pten)
self._pten_hzl = Alteration(self._pten_gene_single_mutation,
"ENST00000371953", "homozygous_loss", None)
self._pten_gene_single_mutation.add_alteration(self._pten_hzl)
self._pten_gene_single_mutation_not_enough = AlteredGene(pten)
self._pten_frameshift = Alteration(
self._pten_gene_single_mutation_not_enough, "ENST00000371953",
"frameshift_variant", None)
self._pten_gene_single_mutation_not_enough.add_alteration(
self._pten_frameshift)
self._pten_gene_double_mutation = AlteredGene(pten)
self._pten_stop_gained = Alteration(self._pten_gene_double_mutation,
"ENST00000371953", "stop_gained",
"p.Gly301Leu")
self._pten_splice_acceptor_variant = Alteration(
self._pten_gene_double_mutation, "ENST00000371953",
"splice_acceptor_variant", "p.Gly10Leu")
self._pten_gene_double_mutation.add_alteration(self._pten_stop_gained)
self._pten_gene_double_mutation.add_alteration(
self._pten_splice_acceptor_variant)
pik3r1 = Gene("PIK3R1")
pik3r1.set_ID("ENSG00000145675")
self._pik3r1_gene_frameshift = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_frameshift = Alteration(self._pik3r1_gene_frameshift,
"ENST00000521381",
"frameshift_variant",
"p.Val351Leu")
self._pik3r1_gene_frameshift.add_alteration(self._pik3r1_frameshift)
self._pik3r1_gene_frameshift_off = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_frameshift_off = Alteration(
self._pik3r1_gene_frameshift_off, "ENST00000521381",
"frameshift_variant", "p.Val10Leu")
self._pik3r1_gene_frameshift_off.add_alteration(
self._pik3r1_frameshift_off)
self._pik3r1_gene_missense = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_missense = Alteration(self._pik3r1_gene_missense,
"ENST00000521381",
"missense_variant", "p.Val376Leu")
self._pik3r1_gene_missense.add_alteration(self._pik3r1_missense)
pik3ca = Gene("PIK3CA")
pik3ca.set_ID("ENSG00000145675")
self._pik3ca_gene_missense1 = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense1 = Alteration(self._pik3ca_gene_missense1,
"ENST00000263967",
"missense_variant", "p.Val38Leu")
self._pik3ca_gene_missense1.add_alteration(self._pik3ca_missense1)
self._pik3ca_gene_missense2 = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense2 = Alteration(self._pik3ca_gene_missense2,
"ENST00000263967",
"missense_variant", "p.Val542Leu")
self._pik3ca_gene_missense2.add_alteration(self._pik3ca_missense2)
self._pik3ca_gene_missense_a_and_b = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense3 = Alteration(self._pik3ca_gene_missense_a_and_b,
"ENST00000263967",
"missense_variant", "p.Val38Leu")
self._pik3ca_missense4 = Alteration(self._pik3ca_gene_missense_a_and_b,
"ENST00000263967",
"missense_variant", "p.Val542Leu")
self._pik3ca_gene_missense_a_and_b.add_alteration(
self._pik3ca_missense3)
self._pik3ca_gene_missense_a_and_b.add_alteration(
self._pik3ca_missense4)
class TestAlasccaClassRule(unittest.TestCase):
def setUp(self):
igf2_classification = AlterationClassification("IGF2",
["amplification"], None,
[], "ALASCCA_CLASS_B_1")
pten_classification_b_2 = AlterationClassification(
"PTEN", [
"start_lost", "stop_gained", "frameshift_variant",
"splice_acceptor_variant", "splice_donor_variant",
"loss_of_heterozygosity"
], "ENST00000371953", [], "ALASCCA_CLASS_B_2")
pten_classification_b_1 = AlterationClassification(
"PTEN", ["homozygous_loss"], "ENST00000371953", [],
"ALASCCA_CLASS_B_1")
pten_classification_b_1_missense = AlterationClassification(
"PTEN", ["missense_variant"], "ENST00000371953",
["p.Cys124Ser", "p.Gly129Glu", "p.Arg130Gly", "p.Arg130Gln"],
"ALASCCA_CLASS_B_1")
pik3r1_classification_b_1 = AlterationClassification(
"PIK3R1", [
"frameshift_variant", "inframe_insertion", "inframe_deletion",
"stop_gained", "splice_acceptor_variant",
"splice_donor_variant"
], "ENST00000521381", ["340:670"], "ALASCCA_CLASS_B_1")
pik3r1_classification_b_1_missense = AlterationClassification(
"PIK3R1", ["missense_variant"], "ENST00000521381", [
"376", "379", "452", "464", "503", "560", "564", "567", "573",
"642"
], "ALASCCA_CLASS_B_1")
pik3ca_classification_b_1 = AlterationClassification(
"PIK3CA", ["missense_variant"], "ENST00000263967", [
"38", "81", "88", "106", "111", "118", "344", "345", "378",
"420", "453", "726"
], "ALASCCA_CLASS_B_1")
pik3ca_classification_a = AlterationClassification(
"PIK3CA", ["missense_variant"], "ENST00000263967",
["542", "545", "546", "1021", "1043", "1044", "1047"],
"ALASCCA_CLASS_A")
self._symbol2classifications = {
"IGF2": [igf2_classification],
"PTEN": [
pten_classification_b_2, pten_classification_b_1,
pten_classification_b_1_missense
],
"PIK3R1":
[pik3r1_classification_b_1, pik3r1_classification_b_1_missense],
"PIK3CA": [pik3ca_classification_b_1, pik3ca_classification_a]
}
pten = Gene("PTEN")
pten.set_ID("ENSG00000171862")
self._pten_gene_single_mutation = AlteredGene(pten)
self._pten_hzl = Alteration(self._pten_gene_single_mutation,
"ENST00000371953", "homozygous_loss", None)
self._pten_gene_single_mutation.add_alteration(self._pten_hzl)
self._pten_gene_single_mutation_not_enough = AlteredGene(pten)
self._pten_frameshift = Alteration(
self._pten_gene_single_mutation_not_enough, "ENST00000371953",
"frameshift_variant", None)
self._pten_gene_single_mutation_not_enough.add_alteration(
self._pten_frameshift)
self._pten_gene_double_mutation = AlteredGene(pten)
self._pten_stop_gained = Alteration(self._pten_gene_double_mutation,
"ENST00000371953", "stop_gained",
"p.Gly301Leu")
self._pten_splice_acceptor_variant = Alteration(
self._pten_gene_double_mutation, "ENST00000371953",
"splice_acceptor_variant", "p.Gly10Leu")
self._pten_gene_double_mutation.add_alteration(self._pten_stop_gained)
self._pten_gene_double_mutation.add_alteration(
self._pten_splice_acceptor_variant)
pik3r1 = Gene("PIK3R1")
pik3r1.set_ID("ENSG00000145675")
self._pik3r1_gene_frameshift = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_frameshift = Alteration(self._pik3r1_gene_frameshift,
"ENST00000521381",
"frameshift_variant",
"p.Val351Leu")
self._pik3r1_gene_frameshift.add_alteration(self._pik3r1_frameshift)
self._pik3r1_gene_frameshift_off = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_frameshift_off = Alteration(
self._pik3r1_gene_frameshift_off, "ENST00000521381",
"frameshift_variant", "p.Val10Leu")
self._pik3r1_gene_frameshift_off.add_alteration(
self._pik3r1_frameshift_off)
self._pik3r1_gene_missense = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_missense = Alteration(self._pik3r1_gene_missense,
"ENST00000521381",
"missense_variant", "p.Val376Leu")
self._pik3r1_gene_missense.add_alteration(self._pik3r1_missense)
pik3ca = Gene("PIK3CA")
pik3ca.set_ID("ENSG00000145675")
self._pik3ca_gene_missense1 = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense1 = Alteration(self._pik3ca_gene_missense1,
"ENST00000263967",
"missense_variant", "p.Val38Leu")
self._pik3ca_gene_missense1.add_alteration(self._pik3ca_missense1)
self._pik3ca_gene_missense2 = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense2 = Alteration(self._pik3ca_gene_missense2,
"ENST00000263967",
"missense_variant", "p.Val542Leu")
self._pik3ca_gene_missense2.add_alteration(self._pik3ca_missense2)
self._pik3ca_gene_missense_a_and_b = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense3 = Alteration(self._pik3ca_gene_missense_a_and_b,
"ENST00000263967",
"missense_variant", "p.Val38Leu")
self._pik3ca_missense4 = Alteration(self._pik3ca_gene_missense_a_and_b,
"ENST00000263967",
"missense_variant", "p.Val542Leu")
self._pik3ca_gene_missense_a_and_b.add_alteration(
self._pik3ca_missense3)
self._pik3ca_gene_missense_a_and_b.add_alteration(
self._pik3ca_missense4)
# def test_init(self):
# rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", {})
# self.assertDictEqual(rule._gene_symbol2classifications, self._symbol2classifications)
def test_apply_single_pten(self):
input_symbol2gene = {"PTEN": self._pten_gene_single_mutation}
rule = AlasccaClassRule(
"reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx",
input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME:
AlasccaClassReport.MUTN_CLASS_B
}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pten_not_enough(self):
input_symbol2gene = {
"PTEN": self._pten_gene_single_mutation_not_enough
}
rule = AlasccaClassRule(
"reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx",
input_symbol2gene)
test_report = rule.apply()
# ALASCCA class definitions changed => This is now Class B.
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME:
AlasccaClassReport.MUTN_CLASS_B
}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3r1_frameshift(self):
input_symbol2gene = {"PIK3R1": self._pik3r1_gene_frameshift}
rule = AlasccaClassRule(
"reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx",
input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME:
AlasccaClassReport.MUTN_CLASS_B
}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3r1_frameshift_off(self):
input_symbol2gene = {"PIK3R1": self._pik3r1_gene_frameshift_off}
rule = AlasccaClassRule(
"reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx",
input_symbol2gene)
test_report = rule.apply()
# ALASCCA class definitions changed => This is now Class B.
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME:
AlasccaClassReport.MUTN_CLASS_B
}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_double_pten(self):
input_symbol2gene = {"PTEN": self._pten_gene_double_mutation}
rule = AlasccaClassRule(
"reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx",
input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME:
AlasccaClassReport.MUTN_CLASS_B
}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3r1_missense(self):
input_symbol2gene = {"PIK3R1": self._pik3r1_gene_missense}
rule = AlasccaClassRule(
"reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx",
input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME:
AlasccaClassReport.MUTN_CLASS_B
}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3ca_class_b(self):
input_symbol2gene = {"PIK3CA": self._pik3ca_gene_missense1}
rule = AlasccaClassRule(
"reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx",
input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME:
AlasccaClassReport.MUTN_CLASS_B
}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3ca_class_a(self):
input_symbol2gene = {"PIK3CA": self._pik3ca_gene_missense2}
rule = AlasccaClassRule(
"reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx",
input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME:
AlasccaClassReport.MUTN_CLASS_A
}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_pik3ca_class_a_test2(self):
input_symbol2gene = {"PIK3CA": self._pik3ca_gene_missense_a_and_b}
rule = AlasccaClassRule(
"reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx",
input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME:
AlasccaClassReport.MUTN_CLASS_A
}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
class TestSimpleSomaticMutationsRule(unittest.TestCase):
def setUp(self):
braf_classification = AlterationClassification("BRAF",
["missense_variant"],
"ENST00000288602",
["p.Val600Glu"],
"BRAF_COMMON")
kras_classification = AlterationClassification(
"KRAS", ["missense_variant"], "ENST00000256078",
["12", "13", "60", "61", "117", "146"], "KRAS_COMMON")
nras_classification = AlterationClassification("NRAS",
["missense_variant"],
"ENST00000369535",
["12", "13", "61"],
"NRAS_COMMON")
self._symbol2classifications = {
"BRAF": [braf_classification],
"KRAS": [kras_classification],
"NRAS": [nras_classification]
}
braf = Gene("BRAF")
braf.set_ID("ENSG00000157764")
self._braf_gene_single_mutation = AlteredGene(braf)
self._braf_alteration3 = Alteration(self._braf_gene_single_mutation,
"ENST00000288602",
"missense_variant", "p.Val600Glu")
self._braf_gene_single_mutation.add_alteration(self._braf_alteration3)
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene_multiple_mutations = AlteredGene(kras)
self._kras_alteration1 = Alteration(self._kras_gene_multiple_mutations,
"ENST00000256078",
"missense_variant", "p.Ala146Pro")
self._kras_gene_multiple_mutations.add_alteration(
self._kras_alteration1)
# Position only specified:
self._kras_alteration2 = Alteration(self._kras_gene_multiple_mutations,
"ENST00000256078",
"missense_variant", "p.Lys117Asn")
self._kras_gene_multiple_mutations.add_alteration(
self._kras_alteration2)
# A fake mutation that is *not* in the set of KRAS mutations:
self._kras_alteration3 = Alteration(self._kras_gene_multiple_mutations,
"ENST00000256078",
"missense_variant", "p.Lys1Asn")
self._kras_gene_multiple_mutations.add_alteration(
self._kras_alteration3)
# def test_classification_is_same(self):
# rule = SimpleSomaticMutationsRule("reportgen/assets/COLORECTAL_MUTATION_TABLE.xlsx", {})
# # FIXME (MAYBE): COULD HAVE THE RIGHT HAND SIDE OF THESE TESTS HARD-CODED INSTEAD OF READ FROM ABOVE.
# # E.g. Test if there are three elements in the first nras gene alteration.
# # XXX CONTINUE HERE: INVESTIGATE THIS APPROACH AS AN ALTERNATIVE TO USING ASSERTDICTEQUAL COMBINED WITH
# # CUSTOM __EQ__ AND __NE__ METHODS.
# self.assertEqual(rule._gene_symbol2classifications["NRAS"][0], self._symbol2classifications["NRAS"][0])
# def test_symbol2classification_is_same(self):
# rule = SimpleSomaticMutationsRule("reportgen/assets/COLORECTAL_MUTATION_TABLE.xlsx", {})
# self.assertDictEqual(rule._gene_symbol2classifications, self._symbol2classifications)
# # Test empty input symbol2gene dictionary:
# def test_apply_empty_input(self):
# # Mock the extract_mutation_spreadsheet_contents function XXX
# rule = SimpleSomaticMutationsRule("dummy_filename", {})
# test_report = rule.apply()
# expected_outdict = {'NRAS': {"status" : 'Not mutated', "alterations": []},
# 'BRAF': {"status" : 'Not mutated', "alterations": []},
# 'KRAS': {"status": 'Not mutated', "alterations" : []}}
# self.assertDictEqual(test_report.to_dict(), expected_outdict)
# Test single mutation symbol2gene input dictionary:
def test_apply_single_mutation_input(self):
input_symbol2gene = {"BRAF": self._braf_gene_single_mutation}
rule = SimpleSomaticMutationsRule(
"reportgen/assets/COLORECTAL_MUTATION_TABLE.xlsx",
input_symbol2gene)
test_report = rule.apply()
expected_outdict = {
'NRAS': {
"status": 'Not mutated',
"alterations": []
},
'BRAF': {
"status": 'Mutated',
"alterations": [{
"hgvsp": 'p.Val600Glu',
"flag": u'BRAF_COMMON'
}]
},
'KRAS': {
"status": 'Not mutated',
"alterations": []
}
}
self.assertDictEqual(test_report.to_dict(), expected_outdict)
# Test multiple genes and multiple mutations symbol2gene input dictionary:
def test_apply_multiple_mutation_input(self):
input_symbol2gene = {
"BRAF": self._braf_gene_single_mutation,
"KRAS": self._kras_gene_multiple_mutations
}
rule = SimpleSomaticMutationsRule(
"reportgen/assets/COLORECTAL_MUTATION_TABLE.xlsx",
input_symbol2gene)
test_report = rule.apply()
expected_outdict = {
'NRAS': {
"status": 'Not mutated',
"alterations": []
},
'BRAF': {
"status": 'Mutated',
"alterations": [{
"hgvsp": 'p.Val600Glu',
"flag": u'BRAF_COMMON'
}]
},
'KRAS': {
"status":
'Mutated',
"alterations": [{
"hgvsp": 'p.Ala146Pro',
"flag": u'KRAS_COMMON'
}, {
"hgvsp": 'p.Lys117Asn',
"flag": u'KRAS_COMMON'
}]
}
}
self.assertDictEqual(test_report.to_dict(), expected_outdict)
def setUp(self):
igf2_classification = AlterationClassification("IGF2", ["amplification"], None, [], "ALASCCA_CLASS_B_1")
pten_classification_b_2 = AlterationClassification("PTEN", ["start_lost", "stop_gained", "frameshift_variant", "splice_acceptor_variant", "splice_donor_variant", "loss_of_heterozygosity"], "ENST00000371953", [], "ALASCCA_CLASS_B_2")
pten_classification_b_1 = AlterationClassification("PTEN", ["homozygous_loss"], "ENST00000371953", [], "ALASCCA_CLASS_B_1")
pten_classification_b_1_missense = AlterationClassification("PTEN", ["missense_variant"], "ENST00000371953", ["p.Cys124Ser", "p.Gly129Glu", "p.Arg130Gly", "p.Arg130Gln"], "ALASCCA_CLASS_B_1")
pik3r1_classification_b_1 = AlterationClassification("PIK3R1", ["frameshift_variant", "inframe_insertion", "inframe_deletion", "stop_gained", "splice_acceptor_variant", "splice_donor_variant"], "ENST00000521381", ["340:670"], "ALASCCA_CLASS_B_1")
pik3r1_classification_b_1_missense = AlterationClassification("PIK3R1", ["missense_variant"], "ENST00000521381", ["376", "379", "452", "464", "503", "560", "564", "567", "573", "642"], "ALASCCA_CLASS_B_1")
pik3ca_classification_b_1 = AlterationClassification("PIK3CA", ["missense_variant"], "ENST00000263967", ["38", "81", "88", "106", "111", "118", "344", "345", "378", "420", "453", "726"], "ALASCCA_CLASS_B_1")
pik3ca_classification_a = AlterationClassification("PIK3CA", ["missense_variant"], "ENST00000263967", ["542", "545", "546", "1021", "1043", "1044", "1047"], "ALASCCA_CLASS_A")
self._symbol2classifications = {"IGF2": [igf2_classification], "PTEN": [pten_classification_b_2, pten_classification_b_1, pten_classification_b_1_missense], "PIK3R1": [pik3r1_classification_b_1, pik3r1_classification_b_1_missense], "PIK3CA": [pik3ca_classification_b_1, pik3ca_classification_a]}
pten = Gene("PTEN")
pten.set_ID("ENSG00000171862")
self._pten_gene_single_mutation = AlteredGene(pten)
self._pten_hzl = Alteration(self._pten_gene_single_mutation, "ENST00000371953", "homozygous_loss", None)
self._pten_gene_single_mutation.add_alteration(self._pten_hzl)
self._pten_gene_single_mutation_not_enough = AlteredGene(pten)
self._pten_frameshift = Alteration(self._pten_gene_single_mutation_not_enough, "ENST00000371953", "frameshift_variant", None)
self._pten_gene_single_mutation_not_enough.add_alteration(self._pten_frameshift)
self._pten_gene_double_mutation = AlteredGene(pten)
self._pten_stop_gained = Alteration(self._pten_gene_double_mutation, "ENST00000371953", "stop_gained", "p.Gly301Leu")
self._pten_splice_acceptor_variant = Alteration(self._pten_gene_double_mutation, "ENST00000371953", "splice_acceptor_variant", "p.Gly10Leu")
self._pten_gene_double_mutation.add_alteration(self._pten_stop_gained)
self._pten_gene_double_mutation.add_alteration(self._pten_splice_acceptor_variant)
pik3r1 = Gene("PIK3R1")
pik3r1.set_ID("ENSG00000145675")
self._pik3r1_gene_frameshift = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_frameshift = Alteration(self._pik3r1_gene_frameshift, "ENST00000521381", "frameshift_variant", "p.Val351Leu")
self._pik3r1_gene_frameshift.add_alteration(self._pik3r1_frameshift)
self._pik3r1_gene_frameshift_off = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_frameshift_off = Alteration(self._pik3r1_gene_frameshift_off, "ENST00000521381", "frameshift_variant", "p.Val10Leu")
self._pik3r1_gene_frameshift_off.add_alteration(self._pik3r1_frameshift_off)
self._pik3r1_gene_missense = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_missense = Alteration(self._pik3r1_gene_missense, "ENST00000521381", "missense_variant", "p.Val376Leu")
self._pik3r1_gene_missense.add_alteration(self._pik3r1_missense)
pik3ca = Gene("PIK3CA")
pik3ca.set_ID("ENSG00000145675")
self._pik3ca_gene_missense1 = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense1 = Alteration(self._pik3ca_gene_missense1, "ENST00000263967", "missense_variant", "p.Val38Leu")
self._pik3ca_gene_missense1.add_alteration(self._pik3ca_missense1)
self._pik3ca_gene_missense2 = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense2 = Alteration(self._pik3ca_gene_missense2, "ENST00000263967", "missense_variant", "p.Val542Leu")
self._pik3ca_gene_missense2.add_alteration(self._pik3ca_missense2)
self._pik3ca_gene_missense_a_and_b = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense3 = Alteration(self._pik3ca_gene_missense_a_and_b, "ENST00000263967", "missense_variant", "p.Val38Leu")
self._pik3ca_missense4 = Alteration(self._pik3ca_gene_missense_a_and_b, "ENST00000263967", "missense_variant", "p.Val542Leu")
self._pik3ca_gene_missense_a_and_b.add_alteration(self._pik3ca_missense3)
self._pik3ca_gene_missense_a_and_b.add_alteration(self._pik3ca_missense4)
class TestAlasccaClassRule(unittest.TestCase):
def setUp(self):
igf2_classification = AlterationClassification("IGF2", ["amplification"], None, [], "ALASCCA_CLASS_B_1")
pten_classification_b_2 = AlterationClassification("PTEN", ["start_lost", "stop_gained", "frameshift_variant", "splice_acceptor_variant", "splice_donor_variant", "loss_of_heterozygosity"], "ENST00000371953", [], "ALASCCA_CLASS_B_2")
pten_classification_b_1 = AlterationClassification("PTEN", ["homozygous_loss"], "ENST00000371953", [], "ALASCCA_CLASS_B_1")
pten_classification_b_1_missense = AlterationClassification("PTEN", ["missense_variant"], "ENST00000371953", ["p.Cys124Ser", "p.Gly129Glu", "p.Arg130Gly", "p.Arg130Gln"], "ALASCCA_CLASS_B_1")
pik3r1_classification_b_1 = AlterationClassification("PIK3R1", ["frameshift_variant", "inframe_insertion", "inframe_deletion", "stop_gained", "splice_acceptor_variant", "splice_donor_variant"], "ENST00000521381", ["340:670"], "ALASCCA_CLASS_B_1")
pik3r1_classification_b_1_missense = AlterationClassification("PIK3R1", ["missense_variant"], "ENST00000521381", ["376", "379", "452", "464", "503", "560", "564", "567", "573", "642"], "ALASCCA_CLASS_B_1")
pik3ca_classification_b_1 = AlterationClassification("PIK3CA", ["missense_variant"], "ENST00000263967", ["38", "81", "88", "106", "111", "118", "344", "345", "378", "420", "453", "726"], "ALASCCA_CLASS_B_1")
pik3ca_classification_a = AlterationClassification("PIK3CA", ["missense_variant"], "ENST00000263967", ["542", "545", "546", "1021", "1043", "1044", "1047"], "ALASCCA_CLASS_A")
self._symbol2classifications = {"IGF2": [igf2_classification], "PTEN": [pten_classification_b_2, pten_classification_b_1, pten_classification_b_1_missense], "PIK3R1": [pik3r1_classification_b_1, pik3r1_classification_b_1_missense], "PIK3CA": [pik3ca_classification_b_1, pik3ca_classification_a]}
pten = Gene("PTEN")
pten.set_ID("ENSG00000171862")
self._pten_gene_single_mutation = AlteredGene(pten)
self._pten_hzl = Alteration(self._pten_gene_single_mutation, "ENST00000371953", "homozygous_loss", None)
self._pten_gene_single_mutation.add_alteration(self._pten_hzl)
self._pten_gene_single_mutation_not_enough = AlteredGene(pten)
self._pten_frameshift = Alteration(self._pten_gene_single_mutation_not_enough, "ENST00000371953", "frameshift_variant", None)
self._pten_gene_single_mutation_not_enough.add_alteration(self._pten_frameshift)
self._pten_gene_double_mutation = AlteredGene(pten)
self._pten_stop_gained = Alteration(self._pten_gene_double_mutation, "ENST00000371953", "stop_gained", "p.Gly301Leu")
self._pten_splice_acceptor_variant = Alteration(self._pten_gene_double_mutation, "ENST00000371953", "splice_acceptor_variant", "p.Gly10Leu")
self._pten_gene_double_mutation.add_alteration(self._pten_stop_gained)
self._pten_gene_double_mutation.add_alteration(self._pten_splice_acceptor_variant)
pik3r1 = Gene("PIK3R1")
pik3r1.set_ID("ENSG00000145675")
self._pik3r1_gene_frameshift = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_frameshift = Alteration(self._pik3r1_gene_frameshift, "ENST00000521381", "frameshift_variant", "p.Val351Leu")
self._pik3r1_gene_frameshift.add_alteration(self._pik3r1_frameshift)
self._pik3r1_gene_frameshift_off = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_frameshift_off = Alteration(self._pik3r1_gene_frameshift_off, "ENST00000521381", "frameshift_variant", "p.Val10Leu")
self._pik3r1_gene_frameshift_off.add_alteration(self._pik3r1_frameshift_off)
self._pik3r1_gene_missense = AlteredGene(pik3r1)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3r1_missense = Alteration(self._pik3r1_gene_missense, "ENST00000521381", "missense_variant", "p.Val376Leu")
self._pik3r1_gene_missense.add_alteration(self._pik3r1_missense)
pik3ca = Gene("PIK3CA")
pik3ca.set_ID("ENSG00000145675")
self._pik3ca_gene_missense1 = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense1 = Alteration(self._pik3ca_gene_missense1, "ENST00000263967", "missense_variant", "p.Val38Leu")
self._pik3ca_gene_missense1.add_alteration(self._pik3ca_missense1)
self._pik3ca_gene_missense2 = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense2 = Alteration(self._pik3ca_gene_missense2, "ENST00000263967", "missense_variant", "p.Val542Leu")
self._pik3ca_gene_missense2.add_alteration(self._pik3ca_missense2)
self._pik3ca_gene_missense_a_and_b = AlteredGene(pik3ca)
# Note: Dummy amino acid change here; the position is important but not
# the actual residue change:
self._pik3ca_missense3 = Alteration(self._pik3ca_gene_missense_a_and_b, "ENST00000263967", "missense_variant", "p.Val38Leu")
self._pik3ca_missense4 = Alteration(self._pik3ca_gene_missense_a_and_b, "ENST00000263967", "missense_variant", "p.Val542Leu")
self._pik3ca_gene_missense_a_and_b.add_alteration(self._pik3ca_missense3)
self._pik3ca_gene_missense_a_and_b.add_alteration(self._pik3ca_missense4)
# def test_init(self):
# rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", {})
# self.assertDictEqual(rule._gene_symbol2classifications, self._symbol2classifications)
def test_apply_single_pten(self):
input_symbol2gene = {"PTEN": self._pten_gene_single_mutation}
rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME: AlasccaClassReport.MUTN_CLASS_B}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pten_not_enough(self):
input_symbol2gene = {"PTEN": self._pten_gene_single_mutation_not_enough}
rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", input_symbol2gene)
test_report = rule.apply()
# ALASCCA class definitions changed => This is now Class B.
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME: AlasccaClassReport.MUTN_CLASS_B}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3r1_frameshift(self):
input_symbol2gene = {"PIK3R1": self._pik3r1_gene_frameshift}
rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME: AlasccaClassReport.MUTN_CLASS_B}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3r1_frameshift_off(self):
input_symbol2gene = {"PIK3R1": self._pik3r1_gene_frameshift_off}
rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", input_symbol2gene)
test_report = rule.apply()
# ALASCCA class definitions changed => This is now Class B.
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME: AlasccaClassReport.MUTN_CLASS_B}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_double_pten(self):
input_symbol2gene = {"PTEN": self._pten_gene_double_mutation}
rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME: AlasccaClassReport.MUTN_CLASS_B}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3r1_missense(self):
input_symbol2gene = {"PIK3R1": self._pik3r1_gene_missense}
rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME: AlasccaClassReport.MUTN_CLASS_B}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3ca_class_b(self):
input_symbol2gene = {"PIK3CA": self._pik3ca_gene_missense1}
rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME: AlasccaClassReport.MUTN_CLASS_B}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_single_pik3ca_class_a(self):
input_symbol2gene = {"PIK3CA": self._pik3ca_gene_missense2}
rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME: AlasccaClassReport.MUTN_CLASS_A}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
def test_apply_pik3ca_class_a_test2(self):
input_symbol2gene = {"PIK3CA": self._pik3ca_gene_missense_a_and_b}
rule = AlasccaClassRule("reportgen/assets/ALASCCA_MUTATION_TABLE_SPECIFIC.xlsx", input_symbol2gene)
test_report = rule.apply()
expected_output_dict = {
AlasccaClassReport.ALASCCA_CLASS_FEATURENAME: AlasccaClassReport.MUTN_CLASS_A}
self.assertDictEqual(test_report.to_dict(), expected_output_dict)
class TestSimpleSomaticMutationsRule(unittest.TestCase):
def setUp(self):
braf_classification = AlterationClassification("BRAF", ["missense_variant"], "ENST00000288602", ["p.Val600Glu"], "BRAF_COMMON")
kras_classification = AlterationClassification("KRAS", ["missense_variant"], "ENST00000256078", ["12", "13", "60", "61", "117", "146"], "KRAS_COMMON")
nras_classification = AlterationClassification("NRAS", ["missense_variant"], "ENST00000369535", ["12", "13", "61"], "NRAS_COMMON")
self._symbol2classifications = {"BRAF": [braf_classification], "KRAS": [kras_classification], "NRAS": [nras_classification]}
braf = Gene("BRAF")
braf.set_ID("ENSG00000157764")
self._braf_gene_single_mutation = AlteredGene(braf)
self._braf_alteration3 = Alteration(self._braf_gene_single_mutation, "ENST00000288602", "missense_variant", "p.Val600Glu")
self._braf_gene_single_mutation.add_alteration(self._braf_alteration3)
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene_multiple_mutations = AlteredGene(kras)
self._kras_alteration1 = Alteration(self._kras_gene_multiple_mutations, "ENST00000256078", "missense_variant", "p.Ala146Pro")
self._kras_gene_multiple_mutations.add_alteration(self._kras_alteration1)
# Position only specified:
self._kras_alteration2 = Alteration(self._kras_gene_multiple_mutations, "ENST00000256078", "missense_variant", "p.Lys117Asn")
self._kras_gene_multiple_mutations.add_alteration(self._kras_alteration2)
# A fake mutation that is *not* in the set of KRAS mutations:
self._kras_alteration3 = Alteration(self._kras_gene_multiple_mutations, "ENST00000256078", "missense_variant", "p.Lys1Asn")
self._kras_gene_multiple_mutations.add_alteration(self._kras_alteration3)
# def test_classification_is_same(self):
# rule = SimpleSomaticMutationsRule("reportgen/assets/COLORECTAL_MUTATION_TABLE.xlsx", {})
# # FIXME (MAYBE): COULD HAVE THE RIGHT HAND SIDE OF THESE TESTS HARD-CODED INSTEAD OF READ FROM ABOVE.
# # E.g. Test if there are three elements in the first nras gene alteration.
# # XXX CONTINUE HERE: INVESTIGATE THIS APPROACH AS AN ALTERNATIVE TO USING ASSERTDICTEQUAL COMBINED WITH
# # CUSTOM __EQ__ AND __NE__ METHODS.
# self.assertEqual(rule._gene_symbol2classifications["NRAS"][0], self._symbol2classifications["NRAS"][0])
# def test_symbol2classification_is_same(self):
# rule = SimpleSomaticMutationsRule("reportgen/assets/COLORECTAL_MUTATION_TABLE.xlsx", {})
# self.assertDictEqual(rule._gene_symbol2classifications, self._symbol2classifications)
# # Test empty input symbol2gene dictionary:
# def test_apply_empty_input(self):
# # Mock the extract_mutation_spreadsheet_contents function XXX
# rule = SimpleSomaticMutationsRule("dummy_filename", {})
# test_report = rule.apply()
# expected_outdict = {'NRAS': {"status" : 'Not mutated', "alterations": []},
# 'BRAF': {"status" : 'Not mutated', "alterations": []},
# 'KRAS': {"status": 'Not mutated', "alterations" : []}}
# self.assertDictEqual(test_report.to_dict(), expected_outdict)
# Test single mutation symbol2gene input dictionary:
def test_apply_single_mutation_input(self):
input_symbol2gene = {"BRAF": self._braf_gene_single_mutation}
rule = SimpleSomaticMutationsRule("reportgen/assets/COLORECTAL_MUTATION_TABLE.xlsx", input_symbol2gene)
test_report = rule.apply()
expected_outdict = {'NRAS': {"status" : 'Not mutated', "alterations": []},
'BRAF': {"status": 'Mutated', "alterations": [{"hgvsp": 'p.Val600Glu', "flag": u'BRAF_COMMON'}]},
'KRAS': {"status": 'Not mutated', "alterations" : []}}
self.assertDictEqual(test_report.to_dict(), expected_outdict)
# Test multiple genes and multiple mutations symbol2gene input dictionary:
def test_apply_multiple_mutation_input(self):
input_symbol2gene = {"BRAF": self._braf_gene_single_mutation, "KRAS": self._kras_gene_multiple_mutations}
rule = SimpleSomaticMutationsRule("reportgen/assets/COLORECTAL_MUTATION_TABLE.xlsx", input_symbol2gene)
test_report = rule.apply()
expected_outdict = {'NRAS': {"status" : 'Not mutated', "alterations": []},
'BRAF': {"status": 'Mutated', "alterations": [{"hgvsp": 'p.Val600Glu', "flag": u'BRAF_COMMON'}]},
'KRAS': {"status": 'Mutated', "alterations" : [{"hgvsp": 'p.Ala146Pro', "flag": u'KRAS_COMMON'},
{"hgvsp": 'p.Lys117Asn', "flag": u'KRAS_COMMON'}]}}
self.assertDictEqual(test_report.to_dict(), expected_outdict)
class TestAlterationClassification(unittest.TestCase):
_single_consequence_classification = None
def setUp(self):
self._braf_classification = AlterationClassification("BRAF", ["missense_variant"], "ENST00000288602", ["p.Val600Glu"], "BRAF_COMMON")
braf = Gene("BRAF")
braf.set_ID("ENSG00000157764")
self._braf_gene = AlteredGene(braf)
self._braf_alteration1 = Alteration(self._braf_gene, "ENST00000288602", "missense_variant", "p.Val600Glu")
self._braf_gene.add_alteration(self._braf_alteration1)
self._kras_classification = AlterationClassification("KRAS", ["missense_variant"], "ENST00000256078", ["12", "13", "60", "61", "117", "146"], "KRAS_COMMON")
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene = AlteredGene(kras)
self._kras_alteration1 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Ala146Pro")
self._kras_gene.add_alteration(self._kras_alteration1)
# A fake mutation whose position is in the set of KRAS mutations:
self._kras_alteration2 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Lys60Pro")
self._kras_gene.add_alteration(self._kras_alteration2)
# A fake mutation that is *not* in the set of KRAS mutations:
self._kras_alteration3 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Lys1Asn")
self._kras_gene.add_alteration(self._kras_alteration3)
self._pik3r1_range_classification = AlterationClassification("PIK3R1", ["inframe_insertion"], "ENST00000521381", ["340:670"], "TEST")
pik3r1 = Gene("PIK3R1")
pik3r1.set_ID("ENSG00000145675")
self._pik3r1_gene = AlteredGene(pik3r1)
# Dummy alteration; position is important, substitution is not:
self._pik3r1_alteration1 = Alteration(self._pik3r1_gene, "ENST00000521381", "inframe_insertion", "p.Val344Lys")
def test_matches_positions_string_vs_string(self):
self.assertTrue(self._braf_classification.matches_positions(self._braf_alteration1))
def test_matches_positions_position_vs_string(self):
self.assertTrue(self._kras_classification.matches_positions(self._kras_alteration1))
def test_matches_positions_position_vs_position(self):
self.assertTrue(self._kras_classification.matches_positions(self._kras_alteration2))
def test_matches_positions_position_vs_string_no_match(self):
self.assertFalse(self._kras_classification.matches_positions(self._kras_alteration3))
def test_match_position_vs_string(self):
self.assertTrue(self._kras_classification.match(self._kras_alteration1))
def test_match_position_vs_string_no_match(self):
self.assertFalse(self._kras_classification.match(self._kras_alteration3))
def test_match_position_in_range(self):
self.assertTrue(self._pik3r1_range_classification.match(self._pik3r1_alteration1))
def test_match_transcript_mismatch(self):
mock_alteration = Mock()
mock_alteration.get_sequence_ontology = Mock(return_value="inframe_insertion")
mock_alteration.get_transcript_ID = Mock(return_value="ENST00000521382")
self.assertFalse(self._pik3r1_range_classification.match(mock_alteration))
def test_matches_positions_no_hgvsp(self):
mock_alteration = Mock()
mock_alteration.get_hgvsp = Mock(return_value=None)
self.assertFalse(self._pik3r1_range_classification.matches_positions(mock_alteration))
class TestAlterationClassification(unittest.TestCase):
_single_consequence_classification = None
def setUp(self):
self._braf_classification = AlterationClassification(
"BRAF", ["missense_variant"], "ENST00000288602", ["p.Val600Glu"],
"BRAF_COMMON")
braf = Gene("BRAF")
braf.set_ID("ENSG00000157764")
self._braf_gene = AlteredGene(braf)
self._braf_alteration1 = Alteration(self._braf_gene, "ENST00000288602",
"missense_variant", "p.Val600Glu")
self._braf_gene.add_alteration(self._braf_alteration1)
self._kras_classification = AlterationClassification(
"KRAS", ["missense_variant"], "ENST00000256078",
["12", "13", "60", "61", "117", "146"], "KRAS_COMMON")
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene = AlteredGene(kras)
self._kras_alteration1 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Ala146Pro")
self._kras_gene.add_alteration(self._kras_alteration1)
# A fake mutation whose position is in the set of KRAS mutations:
self._kras_alteration2 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Lys60Pro")
self._kras_gene.add_alteration(self._kras_alteration2)
# A fake mutation that is *not* in the set of KRAS mutations:
self._kras_alteration3 = Alteration(self._kras_gene, "ENST00000256078",
"missense_variant", "p.Lys1Asn")
self._kras_gene.add_alteration(self._kras_alteration3)
self._pik3r1_range_classification = AlterationClassification(
"PIK3R1", ["inframe_insertion"], "ENST00000521381", ["340:670"],
"TEST")
pik3r1 = Gene("PIK3R1")
pik3r1.set_ID("ENSG00000145675")
self._pik3r1_gene = AlteredGene(pik3r1)
# Dummy alteration; position is important, substitution is not:
self._pik3r1_alteration1 = Alteration(self._pik3r1_gene,
"ENST00000521381",
"inframe_insertion",
"p.Val344Lys")
def test_matches_positions_string_vs_string(self):
self.assertTrue(
self._braf_classification.matches_positions(
self._braf_alteration1))
def test_matches_positions_position_vs_string(self):
self.assertTrue(
self._kras_classification.matches_positions(
self._kras_alteration1))
def test_matches_positions_position_vs_position(self):
self.assertTrue(
self._kras_classification.matches_positions(
self._kras_alteration2))
def test_matches_positions_position_vs_string_no_match(self):
self.assertFalse(
self._kras_classification.matches_positions(
self._kras_alteration3))
def test_match_position_vs_string(self):
self.assertTrue(self._kras_classification.match(
self._kras_alteration1))
def test_match_position_vs_string_no_match(self):
self.assertFalse(
self._kras_classification.match(self._kras_alteration3))
def test_match_position_in_range(self):
self.assertTrue(
self._pik3r1_range_classification.match(self._pik3r1_alteration1))
def test_match_transcript_mismatch(self):
mock_alteration = Mock()
mock_alteration.get_sequence_ontology = Mock(
return_value="inframe_insertion")
mock_alteration.get_transcript_ID = Mock(
return_value="ENST00000521382")
self.assertFalse(
self._pik3r1_range_classification.match(mock_alteration))
def test_matches_positions_no_hgvsp(self):
mock_alteration = Mock()
mock_alteration.get_hgvsp = Mock(return_value=None)
self.assertFalse(
self._pik3r1_range_classification.matches_positions(
mock_alteration))
def setUp(self):
self.test_obj = SimpleSomaticMutationsReport()
self.test_gene_name = "TestGene"
test_gene = Gene(self.test_gene_name)
test_altered_gene = AlteredGene(test_gene)
self.test_mutn = Alteration(test_altered_gene, "TestTranscriptID", "missense_variant", "p.Val1Glu")
class TestAlterationExtractor(unittest.TestCase):
_extractor = None
def setUp(self):
self._extractor = AlterationExtractor()
nras = Gene("NRAS")
nras.set_ID("ENSG00000213281")
self._nras_gene = AlteredGene(nras)
test_alteration1 = Alteration(self._nras_gene, "ENST00000369535", "missense_variant", "p.Gln61His")
self._nras_gene.add_alteration(test_alteration1)
kras = Gene("KRAS")
kras.set_ID("ENSG00000133703")
self._kras_gene = AlteredGene(kras)
test_alteration2 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Ala146Pro")
self._kras_gene.add_alteration(test_alteration2)
test_alteration3 = Alteration(self._kras_gene, "ENST00000256078", "missense_variant", "p.Lys117Asn")
self._kras_gene.add_alteration(test_alteration3)
pten = Gene("PTEN")
pten.set_ID(None)
self._pten_gene_loh = AlteredGene(pten)
test_alteration4 = Alteration(self._pten_gene_loh, None, "loss_of_heterozygosity", None)
self._pten_gene_loh.add_alteration(test_alteration4)
self._pten_gene_hloss = AlteredGene(pten)
test_alteration5 = Alteration(self._pten_gene_hloss, None, "homozygous_loss", None)
self._pten_gene_hloss.add_alteration(test_alteration5)
def test_gene(self):
self._extractor.extract_mutations(open("tests/simple_variant_input.vcf"))
output_dict = self._extractor.to_dict()
self.assertEqual(output_dict["NRAS"].get_gene().get_symbol(), "NRAS")
self.assertEqual(output_dict["NRAS"].get_gene().get_ID(), self._nras_gene.get_gene().get_ID())
def test_extract_mutations_empty_input(self):
self._extractor.extract_mutations(open("tests/empty_input.vcf"))
output_dict = self._extractor.to_dict()
expected_dict = {}
self.assertDictEqual(output_dict, expected_dict)
def test_extract_mutations_empty_input_without_header(self):
self._extractor.extract_mutations(open("tests/empty_input_without_header.vcf"))
output_dict = self._extractor.to_dict()
expected_dict = {}
self.assertDictEqual(output_dict, expected_dict)
def test_extract_mutations_multiple_mutations(self):
self._extractor.extract_mutations(open("tests/multiple_mutations_variant_input.vcf"))
output_dict = self._extractor.to_dict()
expected_dict = {"KRAS": self._kras_gene}
self.assertEqual(len(output_dict.keys()), len(expected_dict.keys()))
self.assertEqual(output_dict["KRAS"].get_gene().get_ID(), expected_dict["KRAS"].get_gene().get_ID())
def test_extract_mutations_multiple_genes(self):
self._extractor.extract_mutations(open("tests/multiple_genes_variant_input.vcf"))
output_dict = self._extractor.to_dict()
expected_dict = {"KRAS": self._kras_gene, "NRAS": self._nras_gene}
self.assertEqual(len(output_dict.keys()), len(expected_dict.keys()))
self.assertEqual(output_dict["NRAS"].get_gene().get_ID(), expected_dict["NRAS"].get_gene().get_ID())
def test_extract_cnvs_gene_no_call(self):
self._extractor.extract_cnvs(open("tests/pten_no_call.json"))
output_dict = self._extractor.to_dict()
# Output dictionary should be empty as there is no call:
self.assertDictEqual(output_dict, {})
def test_extract_cnvs_gene_hom_loss(self):
self._extractor.extract_cnvs(open("tests/pten_hom_loss.json"))
output_dict = self._extractor.to_dict()
# Output dictionary should be empty as there is no call:
self.assertEqual(output_dict["PTEN"].get_gene().get_symbol(), "PTEN")
self.assertEqual(len(output_dict["PTEN"].get_alterations()), 1)
self.assertEqual(output_dict["PTEN"].get_alterations()[0].get_sequence_ontology(), "homozygous_loss")
def test_extract_cnvs_gene_het_loss(self):
self._extractor.extract_cnvs(open("tests/pten_het_loss.json"))
output_dict = self._extractor.to_dict()
# Output dictionary should be empty as there is no call:
self.assertEqual(output_dict["PTEN"].get_gene().get_symbol(), "PTEN")
self.assertEqual(output_dict["PTEN"].get_gene().get_ID(), "ENSG00000171862")
self.assertEqual(len(output_dict["PTEN"].get_alterations()), 1)
self.assertEqual(output_dict["PTEN"].get_alterations()[0].get_sequence_ontology(), "loss_of_heterozygosity")
self.assertEqual(output_dict["PTEN"].get_alterations()[0].get_transcript_ID(), "ENST00000371953")
def test_extract_cnvs_invalid_inputs1(self):
self.assertRaises(ValueError, self._extractor.extract_cnvs, open("tests/pten_invalid_call.json"))