def test_mitochondrial_MTND5_translation_from_cdna():
mtnd5_001 = ensembl_grch38.transcripts_by_name("MT-ND5-201")[0]
cdna = mtnd5_001.coding_sequence
amino_acids, ends_with_stop_codon = translate_cdna(
cdna, first_codon_is_start=True, mitochondrial=True)
assert ends_with_stop_codon
eq_(amino_acids, mtnd5_001.protein_sequence)
def test_sequence_key_with_reading_frame_deletion_with_five_prime_utr():
# Delete second codon of TP53-001, the surrounding context
# includes nucleotides from the 5' UTR. Since TP53 is on the negative
# strand we have to take the reverse complement of the variant which turns
# it into 'CTC'>''
tp53_deletion = Variant("17", 7676589, "CTC", "", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around second codon with 10 context nucleotides:
# In [51]: t.sequence[193-10:193+13]
# Out[51]: 'CACTGCCATGGAGGAGCCGCAGT'
# Which can be split into the following parts:
# last 7 nt of 5' UTR: CACTGCC
# start codon: ATG (translates to M)
# 2nd codon: GAG <---- variant occurs here
# 3rd codon: GAG
# 4th codon: CCG
# 5th codon: CAG
# first nt of 6th codon: T
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_deletion, transcript=tp53_001, context_size=10)
expected = ReferenceCodingSequenceKey(
strand="-",
sequence_before_variant_locus="CACTGCCATG",
sequence_at_variant_locus="GAG",
sequence_after_variant_locus="GAGCCGCAGT",
offset_to_first_complete_codon=7,
contains_start_codon=True,
overlaps_start_codon=True,
contains_five_prime_utr=True,
amino_acids_before_variant="M")
eq_(result, expected)
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_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_with_reading_frame_insertion_context_3nt_no_start():
# Insert nucleotide "T" after second codon of TP53-001,
# but in this test we're going to only keep enough context to see
# the second codon (and no nucleotides from the start). In the reverse
# complement this variant becomes CTC>CTCA.
tp53_insertion = Variant("17", 7676586, "CTC", "CTCA", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around boundary of 2nd/3rd codons
# with 6 context nucleotides:
# 2nd codon: GAG (translates to E)
# <---- insertion variant occurs between these two codons
# 3rd codon: GAG
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=3
)
expected = ReferenceCodingSequenceKey(
strand="-",
sequence_before_variant_locus="GAG",
sequence_at_variant_locus="",
sequence_after_variant_locus="GAG",
offset_to_first_complete_codon=0,
contains_start_codon=False,
overlaps_start_codon=False,
contains_five_prime_utr=False,
amino_acids_before_variant="E",
)
eq_(result, expected)
def test_sequence_key_with_reading_frame_insertion():
# Insert nucleotide "T" after second codon of TP53-001, the
# surrounding context includes nucleotides from the 5' UTR. Since TP53 is on
# the negative strand we have to take the reverse complement of the variant
# which turns it into 'CTC'>'CTCA'
tp53_insertion = Variant("17", 7676586, "CTC", "CTCA", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around boundary of 2nd/3rd codons
# with 10 context nucleotides:
# last 4 nt of 5' UTR: TGCC
# start codon: ATG (translates to M)
# 2nd codon: GAG (translates to E)
# <---- insertion variant occurs between these two codons
# 3rd codon: GAG
# 4th codon: CCG
# 5th codon: CAG
# first nt of 6th codon: T
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=10)
expected = ReferenceCodingSequenceKey(
strand="-",
sequence_before_variant_locus="TGCCATGGAG",
sequence_at_variant_locus="",
sequence_after_variant_locus="GAGCCGCAGT",
offset_to_first_complete_codon=4,
contains_start_codon=True,
overlaps_start_codon=True,
contains_five_prime_utr=True,
amino_acids_before_variant="ME")
eq_(result, expected)
def test_sequence_key_with_reading_frame_deletion_with_five_prime_utr():
# Delete second codon of TP53-001, the surrounding context
# includes nucleotides from the 5' UTR. Since TP53 is on the negative
# strand we have to take the reverse complement of the variant which turns
# it into 'CTC'>''
tp53_deletion = Variant("17", 7676589, "CTC", "", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around second codon with 10 context nucleotides:
# In [51]: t.sequence[193-10:193+13]
# Out[51]: 'CACTGCCATGGAGGAGCCGCAGT'
# Which can be split into the following parts:
# last 7 nt of 5' UTR: CACTGCC
# start codon: ATG (translates to M)
# 2nd codon: GAG <---- variant occurs here
# 3rd codon: GAG
# 4th codon: CCG
# 5th codon: CAG
# first nt of 6th codon: T
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_deletion, transcript=tp53_001, context_size=10
)
expected = ReferenceCodingSequenceKey(
strand="-",
sequence_before_variant_locus="CACTGCCATG",
sequence_at_variant_locus="GAG",
sequence_after_variant_locus="GAGCCGCAGT",
offset_to_first_complete_codon=7,
contains_start_codon=True,
overlaps_start_codon=True,
contains_five_prime_utr=True,
amino_acids_before_variant="M",
)
eq_(result, expected)
def test_sequence_key_with_reading_frame_insertion_context_5nt_overlaps_start(
):
# Insert nucleotide "T" after second codon of TP53-001,
# but in this test we're going to only keep enough context to see
# a part of the start codon, thus the result shouldn't "contain"
# the start codon but does "overlap" it. In the reverse complement
# this variant becomes CTC>CTCA
tp53_insertion = Variant("17", 7676586, "CTC", "CTCA", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around boundary of 2nd/3rd codons
# with 6 context nucleotides:
# last two nt of start codon: TG
# 2nd codon: GAG (translates to E)
# <---- insertion variant occurs between these two codons
# 3rd codon: GAG
# first two nt of 4th codon: CC
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=5)
expected = ReferenceCodingSequenceKey(
strand="-",
sequence_before_variant_locus="TGGAG",
sequence_at_variant_locus="",
sequence_after_variant_locus="GAGCC",
offset_to_first_complete_codon=2,
contains_start_codon=False,
overlaps_start_codon=True,
contains_five_prime_utr=False,
amino_acids_before_variant="E")
eq_(result, expected)
def test_sequence_key_with_reading_frame_insertion_context_5nt_overlaps_start():
# Insert nucleotide "T" after second codon of TP53-001,
# but in this test we're going to only keep enough context to see
# a part of the start codon, thus the result shouldn't "contain"
# the start codon but does "overlap" it. In the reverse complement
# this variant becomes CTC>CTCA
tp53_insertion = Variant("17", 7676586, "CTC", "CTCA", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around boundary of 2nd/3rd codons
# with 6 context nucleotides:
# last two nt of start codon: TG
# 2nd codon: GAG (translates to E)
# <---- insertion variant occurs between these two codons
# 3rd codon: GAG
# first two nt of 4th codon: CC
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=5
)
expected = ReferenceCodingSequenceKey(
strand="-",
sequence_before_variant_locus="TGGAG",
sequence_at_variant_locus="",
sequence_after_variant_locus="GAGCC",
offset_to_first_complete_codon=2,
contains_start_codon=False,
overlaps_start_codon=True,
contains_five_prime_utr=False,
amino_acids_before_variant="E",
)
eq_(result, expected)
def test_sequence_key_with_reading_frame_insertion():
# Insert nucleotide "T" after second codon of TP53-001, the
# surrounding context includes nucleotides from the 5' UTR. Since TP53 is on
# the negative strand we have to take the reverse complement of the variant
# which turns it into 'CTC'>'CTCA'
tp53_insertion = Variant("17", 7676586, "CTC", "CTCA", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around boundary of 2nd/3rd codons
# with 10 context nucleotides:
# last 4 nt of 5' UTR: TGCC
# start codon: ATG (translates to M)
# 2nd codon: GAG (translates to E)
# <---- insertion variant occurs between these two codons
# 3rd codon: GAG
# 4th codon: CCG
# 5th codon: CAG
# first nt of 6th codon: T
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=10
)
expected = ReferenceCodingSequenceKey(
strand="-",
sequence_before_variant_locus="TGCCATGGAG",
sequence_at_variant_locus="",
sequence_after_variant_locus="GAGCCGCAGT",
offset_to_first_complete_codon=4,
contains_start_codon=True,
overlaps_start_codon=True,
contains_five_prime_utr=True,
amino_acids_before_variant="ME",
)
eq_(result, expected)
def test_sequence_key_with_reading_frame_insertion_context_3nt_no_start():
# Insert nucleotide "T" after second codon of TP53-001,
# but in this test we're going to only keep enough context to see
# the second codon (and no nucleotides from the start). In the reverse
# complement this variant becomes CTC>CTCA.
tp53_insertion = Variant("17", 7676586, "CTC", "CTCA", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around boundary of 2nd/3rd codons
# with 6 context nucleotides:
# 2nd codon: GAG (translates to E)
# <---- insertion variant occurs between these two codons
# 3rd codon: GAG
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=3)
expected = ReferenceCodingSequenceKey(strand="-",
sequence_before_variant_locus="GAG",
sequence_at_variant_locus="",
sequence_after_variant_locus="GAG",
offset_to_first_complete_codon=0,
contains_start_codon=False,
overlaps_start_codon=False,
contains_five_prime_utr=False,
amino_acids_before_variant="E")
eq_(result, expected)
def test_TP53_translation_from_cdna():
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
cdna = tp53_001.coding_sequence
amino_acids, ends_with_stop_codon = translate_cdna(
cdna, first_codon_is_start=True)
assert ends_with_stop_codon
eq_(amino_acids, tp53_001.protein_sequence)
def test_interbase_range_for_brca2_utr_insertion():
# T>TC insertion after the 6th nucleotide of BRCA2-001's 5' UTR
brca2_insertion = Variant("13", 32315479, "T", "TC", ensembl_grch38)
brca2_001 = ensembl_grch38.transcripts_by_name("BRCA2-001")[0]
interbase_range = interbase_range_affected_by_variant_on_transcript(
variant=brca2_insertion, transcript=brca2_001)
print(interbase_range)
eq_(interbase_range, (6, 6))
def test_mitochondrial_MTND5_translation_from_cdna():
mtnd5_001 = ensembl_grch38.transcripts_by_name("MT-ND5-201")[0]
cdna = mtnd5_001.coding_sequence
amino_acids, ends_with_stop_codon = translate_cdna(
cdna,
first_codon_is_start=True,
mitochondrial=True)
assert ends_with_stop_codon
eq_(amino_acids, mtnd5_001.protein_sequence)
def test_interbase_range_for_brca2_utr_insertion():
# T>TC insertion after the 6th nucleotide of BRCA2-001's 5' UTR
brca2_insertion = Variant("13", 32315479, "T", "TC", ensembl_grch38)
brca2_001 = ensembl_grch38.transcripts_by_name("BRCA2-001")[0]
interbase_range = interbase_range_affected_by_variant_on_transcript(
variant=brca2_insertion,
transcript=brca2_001)
print(interbase_range)
eq_(interbase_range, (6, 6))
def test_sequence_key_with_reading_frame_insertion_before_start_codon():
# insert nucleotide "T" before of the start codon of TP53-001,
tp53_insertion = Variant("17", 7676593, "C", "CT", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=1)
assert result is None, "Expected result to be None when variant before start codon"
def test_sequence_key_with_reading_frame_insertion_before_start_codon():
# insert nucleotide "T" before of the start codon of TP53-001,
tp53_insertion = Variant("17", 7676593, "C", "CT", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=1
)
assert result is None, "Expected result to be None when variant before start codon"
def test_interbase_range_for_brca2_utr_substitution():
# rs769125639 is a simple T>A substitution in the 6th nucleotide of
# BRCA2-001's 5' UTR
brca2_variant_rs769125639 = Variant("13", 32315479, "T", "A",
ensembl_grch38)
brca2_001 = ensembl_grch38.transcripts_by_name("BRCA2-001")[0]
interbase_range = interbase_range_affected_by_variant_on_transcript(
variant=brca2_variant_rs769125639, transcript=brca2_001)
print(interbase_range)
eq_(interbase_range, (5, 6))
def test_reference_coding_sequence_key_insertion_inside_start_codon():
# insert nucleotide "C" in the middle of the start codon of TP53-001,
# keeping only 1 nucleotide of context. In the reverse complement this
# becomes 'T'>'TG'
tp53_insertion = Variant("17", 7676592, "T", "TG", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=1)
assert result is None, "Expected result to be None when variant affects start codon"
def test_interbase_range_for_brca2_utr_substitution():
# rs769125639 is a simple T>A substitution in the 6th nucleotide of
# BRCA2-001's 5' UTR
brca2_variant_rs769125639 = Variant(
"13", 32315479, "T", "A", ensembl_grch38)
brca2_001 = ensembl_grch38.transcripts_by_name("BRCA2-001")[0]
interbase_range = interbase_range_affected_by_variant_on_transcript(
variant=brca2_variant_rs769125639,
transcript=brca2_001)
print(interbase_range)
eq_(interbase_range, (5, 6))
def test_reference_coding_sequence_key_insertion_inside_start_codon():
# insert nucleotide "C" in the middle of the start codon of TP53-001,
# keeping only 1 nucleotide of context. In the reverse complement this
# becomes 'T'>'TG'
tp53_insertion = Variant("17", 7676592, "T", "TG", ensembl_grch38)
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
result = ReferenceCodingSequenceKey.from_variant_and_transcript(
variant=tp53_insertion, transcript=tp53_001, context_size=1
)
assert result is None, "Expected result to be None when variant affects start codon"
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_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_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():
# 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)
def test_TP53_translation_from_cdna():
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
cdna = tp53_001.coding_sequence
amino_acids, ends_with_stop_codon = translate_cdna(cdna, first_codon_is_start=True)
assert ends_with_stop_codon
eq_(amino_acids, tp53_001.protein_sequence)
def test_sequence_key_with_reading_frame_substitution_on_negative_strand():
# replace second codon of TP53-001 with 'CCC'
tp53_substitution = Variant(
"17", 7676589, "CTC", "GGG", ensembl_grch38)
variant_collection = VariantCollection([tp53_substitution])
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around second codon with 10 context nucleotides:
# In [51]: t.sequence[193-10:193+13]
# Out[51]: 'CACTGCCATGGAGGAGCCGCAGT'
# Which can be split into the following parts:
# last 7 nt of 5' UTR: CACTGCC
# start codon: ATG (translates to M)
# 2nd codon: GAG <---- variant occurs here
# 3rd codon: GAG
# 4th codon: CCG
# 5th codon: CAG
# first nt of 6th codon: T
# first calling without a transcript ID white to see if we get back
# multiple contexts
reference_context_dict_many_transcripts = \
reference_contexts_for_variants(
variants=variant_collection,
context_size=10,
transcript_id_whitelist=None)
assert len(reference_context_dict_many_transcripts) == 1, \
"Dictionary should have only one variant but got %d keys" % (
len(reference_context_dict_many_transcripts),)
reference_contexts = reference_context_dict_many_transcripts[tp53_substitution]
assert len(reference_contexts) > 1, \
"Expected multiple reference contexts for %s but got %d: %s" % (
tp53_substitution,
len(reference_contexts),
reference_contexts)
reference_context_dict_single_transcript = \
reference_contexts_for_variants(
variants=variant_collection,
context_size=10,
transcript_id_whitelist={tp53_001.id})
# still only expect one variant key
eq_(len(reference_context_dict_single_transcript), 1)
result_list = reference_context_dict_single_transcript[tp53_substitution]
# since we limited the transcript ID whitelist, we only expect a single
# reference context in the result
eq_(len(result_list), 1)
result = result_list[0]
expected = ReferenceContext(
strand="-",
sequence_before_variant_locus="CACTGCCATG",
sequence_at_variant_locus="GAG",
sequence_after_variant_locus="GAGCCGCAGT",
offset_to_first_complete_codon=7,
contains_start_codon=True,
overlaps_start_codon=True,
contains_five_prime_utr=True,
amino_acids_before_variant="M",
variant=tp53_substitution,
transcripts=[tp53_001])
eq_(result, expected)
def test_sequence_key_with_reading_frame_substitution_on_negative_strand():
# replace second codon of TP53-001 with 'CCC'
tp53_substitution = Variant("17", 7676589, "CTC", "GGG", ensembl_grch38)
variant_collection = VariantCollection([tp53_substitution])
tp53_001 = ensembl_grch38.transcripts_by_name("TP53-001")[0]
# Sequence of TP53 around second codon with 10 context nucleotides:
# In [51]: t.sequence[193-10:193+13]
# Out[51]: 'CACTGCCATGGAGGAGCCGCAGT'
# Which can be split into the following parts:
# last 7 nt of 5' UTR: CACTGCC
# start codon: ATG (translates to M)
# 2nd codon: GAG <---- variant occurs here
# 3rd codon: GAG
# 4th codon: CCG
# 5th codon: CAG
# first nt of 6th codon: T
# first calling without a transcript ID white to see if we get back
# multiple contexts
reference_context_dict_many_transcripts = \
reference_contexts_for_variants(
variants=variant_collection,
context_size=10,
transcript_id_whitelist=None)
assert len(reference_context_dict_many_transcripts) == 1, \
"Dictionary should have only one variant but got %d keys" % (
len(reference_context_dict_many_transcripts),)
reference_contexts = reference_context_dict_many_transcripts[
tp53_substitution]
assert len(reference_contexts) > 1, \
"Expected multiple reference contexts for %s but got %d: %s" % (
tp53_substitution,
len(reference_contexts),
reference_contexts)
reference_context_dict_single_transcript = \
reference_contexts_for_variants(
variants=variant_collection,
context_size=10,
transcript_id_whitelist={tp53_001.id})
# still only expect one variant key
eq_(len(reference_context_dict_single_transcript), 1)
result_list = reference_context_dict_single_transcript[tp53_substitution]
# since we limited the transcript ID whitelist, we only expect a single
# reference context in the result
eq_(len(result_list), 1)
result = result_list[0]
expected = ReferenceContext(strand="-",
sequence_before_variant_locus="CACTGCCATG",
sequence_at_variant_locus="GAG",
sequence_after_variant_locus="GAGCCGCAGT",
offset_to_first_complete_codon=7,
contains_start_codon=True,
overlaps_start_codon=True,
contains_five_prime_utr=True,
amino_acids_before_variant="M",
variant=tp53_substitution,
transcripts=[tp53_001])
eq_(result, expected)
def test_protein_protein_sequence():
transcript = ensembl_grch38.transcripts_by_name("EGFR-001")[0]
eq_(transcript.protein_sequence, EGFR_001_protein_sequence)
def test_protein_id():
transcript = ensembl_grch38.transcripts_by_name("EGFR-001")[0]
eq_(transcript.protein_id, "ENSP00000275493")
def test_protein_id():
transcript = ensembl_grch38.transcripts_by_name("EGFR-001")[0]
eq_(transcript.protein_id, "ENSP00000275493")
def test_protein_protein_sequence():
transcript = ensembl_grch38.transcripts_by_name("EGFR-001")[0]
eq_(transcript.protein_sequence, EGFR_001_protein_sequence)