def test_sequence_key_for_variant_on_transcript_insertion_reverse_strand():
# insert 'CCC' after start codon of TP53-001, which on the reverse
# complement means inserting "GGG" between "CTC_CAT"
tp53_insertion = Variant("17", 7676589, "CTC", "CTCGGG", grch38)
tp53_001 = grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around start codon with 10 context nucleotides:
# In [51]: t.sequence[190-10:190+13]
# Out[51]: 'GGTCACTGCC_ATG_GAGGAGCCGC'
eq_(tp53_001.sequence[190 - 10:190 + 13], "GGTCACTGCCATGGAGGAGCCGC")
# The above gives us the cDNA sequence from the transcript, whereas the
# reverse complement genomic sequence is:
# GCGGCTCCTC_CAT_GGCAGTGACC
# get the 5 nucleotides before the variant and 10 nucleotides after
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=tp53_insertion,
transcript=tp53_001,
context_size=10)
expected_sequence_key = ReferenceSequenceKey(
strand="-",
sequence_before_variant_locus="CACTGCCATG",
sequence_at_variant_locus="",
sequence_after_variant_locus="GAGGAGCCGC")
eq_(sequence_key, expected_sequence_key)
def test_reference_sequence_key_hash_and_equality_same_objects():
rsk1 = ReferenceSequenceKey(strand="+",
sequence_before_variant_locus="AAA",
sequence_at_variant_locus="T",
sequence_after_variant_locus="GGG")
rsk2 = ReferenceSequenceKey(strand="+",
sequence_before_variant_locus="AAA",
sequence_at_variant_locus="T",
sequence_after_variant_locus="GGG")
eq_(rsk1, rsk2)
eq_(hash(rsk1), hash(rsk2))
eq_(str(rsk1), str(rsk2))
eq_(repr(rsk1), repr(rsk2))
def test_reference_sequence_key_hash_and_equality_different_objects():
rsk1 = ReferenceSequenceKey(strand="+",
sequence_before_variant_locus="AAA",
sequence_at_variant_locus="T",
sequence_after_variant_locus="GGG")
rsk_different_strand = ReferenceSequenceKey(
strand="-",
sequence_before_variant_locus="AAA",
sequence_at_variant_locus="T",
sequence_after_variant_locus="GGG")
assert rsk1 != rsk_different_strand
assert hash(rsk1) != hash(rsk_different_strand)
assert str(rsk1) != str(rsk_different_strand)
assert repr(rsk1) != repr(rsk_different_strand)
def test_sequence_key_for_variant_on_transcript_insertion_reverse_strand():
# insert 'CCC' after start codon of TP53-001, which on the reverse
# complement means inserting "GGG" between "CTC_CAT"
tp53_insertion = Variant(
"17", 7676589, "CTC", "CTCGGG", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around start codon with 10 context nucleotides:
# In [51]: t.sequence[190-10:190+13]
# Out[51]: 'GGTCACTGCC_ATG_GAGGAGCCGC'
eq_(tp53_001.sequence[190 - 10:190 + 13], "GGTCACTGCCATGGAGGAGCCGC")
# The above gives us the cDNA sequence from the transcript, whereas the
# reverse complement genomic sequence is:
# GCGGCTCCTC_CAT_GGCAGTGACC
# get the 5 nucleotides before the variant and 10 nucleotides after
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=tp53_insertion,
transcript=tp53_001,
context_size=10)
expected_sequence_key = ReferenceSequenceKey(
strand="-",
sequence_before_variant_locus="CACTGCCATG",
sequence_at_variant_locus="",
sequence_after_variant_locus="GAGGAGCCGC")
eq_(sequence_key, expected_sequence_key)
def test_sequence_key_for_variant_on_transcript_deletion():
# Delete the 6th nucleotide of BRCA2-001's 5' UTR
brca2_variant_deletion = Variant("13", 32315479, "T", "", ensembl_grch38)
brca2_001 = ensembl_grch38.transcripts_by_name("BRCA2-001")[0]
# first 50 characters of BRCA2-001:
# "GGGCTTGTGGCGCGAGCTTCTGAAACTAGGCGGCAGAGGCGGAGCCGCTG"
brca2_ref_seq = brca2_001.sequence[:50]
eq_(brca2_ref_seq, "GGGCTTGTGGCGCGAGCTTCTGAAACTAGGCGGCAGAGGCGGAGCCGCTG")
print(brca2_ref_seq)
# get the 5 nucleotides before the variant and 10 nucleotides after
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=brca2_variant_deletion, transcript=brca2_001, context_size=10)
expected_sequence_key = ReferenceSequenceKey(
strand="+",
sequence_before_variant_locus=brca2_ref_seq[:5],
sequence_at_variant_locus="T",
sequence_after_variant_locus=brca2_ref_seq[6:16])
eq_(sequence_key, expected_sequence_key)
def test_reference_sequence_key_from_weird_deletion():
# variant reads into the intron; want to make sure isovar skips over such cases
variant = Variant("11", 106262686, "GTGAAGG", "", grcm38)
transcript = grcm38.transcript_by_id("ENSMUST00000021049")
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=variant,
transcript=transcript,
context_size=10)
assert sequence_key is None, '%s\n%s' % (sequence_key, transcript)
def test_sequence_key_for_variant_on_transcript_substitution_reverse_strand():
# Replace start codon of TP53-001 with 'CCC', however since this is on
# reverse strand the variant becomes "CAT">"GGG"
tp53_substitution = Variant("17", 7676592, "CAT", "GGG", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around start codon with 10 context nucleotides:
# In [51]: t.sequence[190-10:190+13]
# Out[51]: 'GGTCACTGCC_ATG_GAGGAGCCGC'
eq_(tp53_001.sequence[190 - 10:190 + 13], "GGTCACTGCCATGGAGGAGCCGC")
# get the 5 nucleotides before the variant and 10 nucleotides after
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=tp53_substitution, transcript=tp53_001, context_size=10)
expected_sequence_key = ReferenceSequenceKey(
strand="-",
sequence_before_variant_locus="GGTCACTGCC",
sequence_at_variant_locus="ATG",
sequence_after_variant_locus="GAGGAGCCGC")
eq_(sequence_key, expected_sequence_key)
def test_sequence_key_for_variant_on_transcript_deletion_reverse_strand():
# delete start codon of TP53-001, which in reverse complement means
# deleting the sequence "CAT"
tp53_deletion = Variant("17", 7676592, "CAT", "", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around start codon with 10 context nucleotides:
# In [51]: t.sequence[190-10:190+13]
# Out[51]: 'GGTCACTGCC_ATG_GAGGAGCCGC'
eq_(tp53_001.sequence[190 - 10:190 + 13], "GGTCACTGCCATGGAGGAGCCGC")
# get the 5 nucleotides before the variant and 10 nucleotides after
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=tp53_deletion, transcript=tp53_001, context_size=10)
expected_sequence_key = ReferenceSequenceKey(
strand="-",
sequence_before_variant_locus="GGTCACTGCC",
sequence_at_variant_locus="ATG",
sequence_after_variant_locus="GAGGAGCCGC")
eq_(sequence_key, expected_sequence_key)
def test_sequence_key_for_variant_on_transcript_insertion():
# Insert 'CCC' after the 6th nucleotide of BRCA2-001's 5' UTR
brca2_variant_insertion = Variant(
"13", 32315479, "T", "TCCC", grch38)
brca2_001 = grch38.transcripts_by_name("BRCA2-001")[0]
# first 50 characters of BRCA2-001:
# "GGGCTTGTGGCGCGAGCTTCTGAAACTAGGCGGCAGAGGCGGAGCCGCTG"
brca2_ref_seq = brca2_001.sequence[:50]
eq_(brca2_ref_seq, "GGGCTTGTGGCGCGAGCTTCTGAAACTAGGCGGCAGAGGCGGAGCCGCTG")
print(brca2_ref_seq)
# get the 5 nucleotides before the variant and 10 nucleotides after
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=brca2_variant_insertion,
transcript=brca2_001,
context_size=10)
# expecting nothing at the variant locus since we're inserting between
# two reference nucleotides
expected_sequence_key = ReferenceSequenceKey(
strand="+",
sequence_before_variant_locus=brca2_ref_seq[:6],
sequence_at_variant_locus="",
sequence_after_variant_locus=brca2_ref_seq[6:16])
eq_(sequence_key, expected_sequence_key)
def test_sequence_key_for_variant_on_transcript_deletion():
# Delete the 6th nucleotide of BRCA2-001's 5' UTR
brca2_variant_deletion = Variant(
"13", 32315479, "T", "", ensembl_grch38)
brca2_001 = ensembl_grch38.transcripts_by_name("BRCA2-001")[0]
# first 50 characters of BRCA2-001:
# "GGGCTTGTGGCGCGAGCTTCTGAAACTAGGCGGCAGAGGCGGAGCCGCTG"
brca2_ref_seq = brca2_001.sequence[:50]
eq_(brca2_ref_seq, "GGGCTTGTGGCGCGAGCTTCTGAAACTAGGCGGCAGAGGCGGAGCCGCTG")
print(brca2_ref_seq)
# get the 5 nucleotides before the variant and 10 nucleotides after
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=brca2_variant_deletion,
transcript=brca2_001,
context_size=10)
expected_sequence_key = ReferenceSequenceKey(
strand="+",
sequence_before_variant_locus=brca2_ref_seq[:5],
sequence_at_variant_locus="T",
sequence_after_variant_locus=brca2_ref_seq[6:16])
eq_(sequence_key, expected_sequence_key)
def test_sequence_key_for_variant_on_transcript_substitution_reverse_strand():
# Replace start codon of TP53-001 with 'CCC', however since this is on
# reverse strand the variant becomes "CAT">"GGG"
tp53_substitution = Variant(
"17", 7676592, "CAT", "GGG", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around start codon with 10 context nucleotides:
# In [51]: t.sequence[190-10:190+13]
# Out[51]: 'GGTCACTGCC_ATG_GAGGAGCCGC'
eq_(tp53_001.sequence[190 - 10:190 + 13], "GGTCACTGCCATGGAGGAGCCGC")
# get the 5 nucleotides before the variant and 10 nucleotides after
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=tp53_substitution,
transcript=tp53_001,
context_size=10)
expected_sequence_key = ReferenceSequenceKey(
strand="-",
sequence_before_variant_locus="GGTCACTGCC",
sequence_at_variant_locus="ATG",
sequence_after_variant_locus="GAGGAGCCGC")
eq_(sequence_key, expected_sequence_key)
def test_sequence_key_for_variant_on_transcript_deletion_reverse_strand():
# delete start codon of TP53-001, which in reverse complement means
# deleting the sequence "CAT"
tp53_deletion = Variant(
"17", 7676592, "CAT", "", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around start codon with 10 context nucleotides:
# In [51]: t.sequence[190-10:190+13]
# Out[51]: 'GGTCACTGCC_ATG_GAGGAGCCGC'
eq_(tp53_001.sequence[190 - 10:190 + 13], "GGTCACTGCCATGGAGGAGCCGC")
# get the 5 nucleotides before the variant and 10 nucleotides after
sequence_key = ReferenceSequenceKey.from_variant_and_transcript(
variant=tp53_deletion,
transcript=tp53_001,
context_size=10)
expected_sequence_key = ReferenceSequenceKey(
strand="-",
sequence_before_variant_locus="GGTCACTGCC",
sequence_at_variant_locus="ATG",
sequence_after_variant_locus="GAGGAGCCGC")
eq_(sequence_key, expected_sequence_key)
