def _calculate_protein_sequence(self, exons, seq, cds_start_genomic_space, cds_stop_genomic_space, strand):
cds_start_exon_space, cds_stop_exon_space = TranscriptProviderUtils._convert_genomic_space_to_feature_space(int(cds_start_genomic_space), int(cds_stop_genomic_space), exons, strand)
prot_seq = MutUtils.translate_sequence(seq[int(cds_start_exon_space):int(cds_stop_exon_space)])
if len(prot_seq) > 0 and prot_seq[-1] == '*':
prot_seq = prot_seq[:-1]
return prot_seq
def _calculate_protein_sequence(self, exons, seq, cds_start_genomic_space,
cds_stop_genomic_space, strand):
cds_start_exon_space, cds_stop_exon_space = TranscriptProviderUtils._convert_genomic_space_to_feature_space(
int(cds_start_genomic_space), int(cds_stop_genomic_space), exons,
strand)
prot_seq = MutUtils.translate_sequence(
seq[int(cds_start_exon_space):int(cds_stop_exon_space)])
if len(prot_seq) > 0 and prot_seq[-1] == '*':
prot_seq = prot_seq[:-1]
return prot_seq
def get_protein_seq(self, transcript_id):
gaf_record = self.get_transcript(transcript_id)
tx_seq = self.get_transcript_seq(transcript_id)
if not gaf_record or not tx_seq:
return None
if 'cds_start' not in gaf_record or not gaf_record['cds_start']:
return None
prot_seq = MutUtils.translate_sequence(tx_seq[gaf_record['cds_start']-1:gaf_record['cds_stop']])
if prot_seq[-1] == '*':
prot_seq = prot_seq[:-1]
return prot_seq
def get_protein_seq(self, transcript_id):
gaf_record = self.get_transcript(transcript_id)
tx_seq = self.get_transcript_seq(transcript_id)
if not gaf_record or not tx_seq:
return None
if 'cds_start' not in gaf_record or not gaf_record['cds_start']:
return None
prot_seq = MutUtils.translate_sequence(
tx_seq[gaf_record['cds_start'] - 1:gaf_record['cds_stop']])
if prot_seq[-1] == '*':
prot_seq = prot_seq[:-1]
return prot_seq
def _determine_vc_for_cds_overlap(self, start, end, ref_allele, alt_allele,
is_frameshift_indel, is_splice_site, tx,
variant_type, is_start_codon):
"""
Note: This method can also handle start and stop codons.
:param start:
:param end:
:param ref_allele:
:param alt_allele:
:param is_frameshift_indel:
:param is_splice_site:
:param tx:
:param variant_type:
:return:
"""
observed_allele_stranded, reference_allele_stranded = self._get_stranded_alleles(
ref_allele, alt_allele, tx)
transcript_position_start, transcript_position_end = TranscriptProviderUtils.convert_genomic_space_to_exon_space(
start, end, tx)
if tx.get_strand(
) == "+" and not variant_type == VariantClassification.VT_INS:
transcript_position_start -= 1
transcript_position_end -= 1
transcript_seq = tx.get_seq()
protein_seq = tx.get_protein_seq()
cds_start, cds_stop = TranscriptProviderUtils.determine_cds_in_exon_space(
tx)
protein_position_start, protein_position_end = TranscriptProviderUtils.get_protein_positions(
transcript_position_start, transcript_position_end, cds_start)
new_ref_transcript_seq = transcript_seq
if (transcript_seq[transcript_position_start:transcript_position_end +
1] != reference_allele_stranded
) and variant_type != VariantClassification.VT_INS:
new_ref_transcript_seq = list(transcript_seq)
new_ref_transcript_seq[
transcript_position_start:transcript_position_end +
1] = reference_allele_stranded
new_ref_transcript_seq = ''.join(new_ref_transcript_seq)
ref_tx_seq_has_been_changed = True
else:
ref_tx_seq_has_been_changed = False
cds_codon_start, cds_codon_end = TranscriptProviderUtils.get_cds_codon_positions(
protein_position_start, protein_position_end, cds_start)
if variant_type == "DEL":
reference_codon_seq = new_ref_transcript_seq[
cds_codon_start:cds_codon_end + 1].lower()
else:
reference_codon_seq = TranscriptProviderUtils.mutate_reference_sequence(
new_ref_transcript_seq[cds_codon_start:cds_codon_end +
1].lower(), cds_codon_start,
transcript_position_start, transcript_position_end,
reference_allele_stranded, variant_type)
if variant_type == "INS" and tx.get_strand() == "-":
mutated_codon_seq = TranscriptProviderUtils.mutate_reference_sequence(
reference_codon_seq.lower(), cds_codon_start - 1,
transcript_position_start, transcript_position_end,
observed_allele_stranded, variant_type)
else:
mutated_codon_seq = TranscriptProviderUtils.mutate_reference_sequence(
reference_codon_seq.lower(), cds_codon_start,
transcript_position_start, transcript_position_end,
observed_allele_stranded, variant_type)
observed_aa = MutUtils.translate_sequence(mutated_codon_seq)
if ref_tx_seq_has_been_changed:
reference_aa = MutUtils.translate_sequence(reference_codon_seq)
else:
reference_aa = protein_seq[protein_position_start -
1:protein_position_end]
if variant_type != VariantClassification.VT_SNP:
try:
reference_aa, observed_aa, protein_position_start, protein_position_end = \
self._adjust_protein_position_and_alleles(protein_seq, protein_position_start,
protein_position_end, reference_aa, observed_aa)
except InvalidVariantException as ive:
logging.getLogger(__name__).error(
"Could not properly adjust protein position for variant: %s, %s, %s, %s, %s VT: %s"
% (tx.get_contig(), start, end, ref_allele, alt_allele,
variant_type))
logging.getLogger(__name__).error(str(ive))
logging.getLogger(__name__).warn(
"Above error may not have exact start and end positions if this is a VCF input."
)
logging.getLogger(__name__).warn(
"Variant type is likely incorrect. This can happen with some GATK VCFs"
)
logging.getLogger(__name__).warn(
TranscriptProviderUtils.is_valid_xNP(
variant_type, ref_allele, alt_allele))
logging.getLogger(__name__).warn(
"The protein_change annotation may not be properly rendered."
)
vc_tmp, vc_tmp_secondary = self.infer_variant_classification(
variant_type,
reference_aa,
observed_aa,
ref_allele,
alt_allele,
is_frameshift_indel=is_frameshift_indel,
is_splice_site=is_splice_site,
is_start_codon=is_start_codon)
cds_start_exon_space, cds_end_exon_space = TranscriptProviderUtils.determine_cds_in_exon_space(
tx)
exon_i = TranscriptProviderUtils.determine_exon_index(
int(start), int(end), tx, variant_type)
final_vc = VariantClassification(
vc_tmp,
variant_type,
transcript_id=tx.get_transcript_id(),
alt_codon=mutated_codon_seq,
ref_codon=reference_codon_seq,
ref_aa=reference_aa,
ref_protein_start=protein_position_start,
ref_protein_end=protein_position_end,
alt_aa=observed_aa,
alt_codon_start_in_exon=cds_codon_start,
alt_codon_end_in_exon=cds_codon_end,
ref_codon_start_in_exon=cds_codon_start,
ref_codon_end_in_exon=cds_codon_end,
cds_start_in_exon_space=cds_start_exon_space,
ref_allele_stranded=reference_allele_stranded,
alt_allele_stranded=observed_allele_stranded,
exon_i=exon_i,
vc_secondary=vc_tmp_secondary)
return final_vc
