def variant_classify(self, tx, ref_allele, alt_allele, start, end, variant_type, dist=2):
"""Perform classifications.
Everything handled in genomic space
*RNA*
x'UTR
Splice_Site (Intron)
Intron
Splice_Site (Exon)
{Missense, Silent}
{Nonsense, Silent}
{Nonstop, Silent}
IGR
x'Flank
De_novo_Start
"""
gene_type = tx.get_gene_type()
if gene_type != "protein_coding":
if gene_type == VariantClassification.LINCRNA:
return VariantClassification(VariantClassification.LINCRNA, variant_type, tx.get_transcript_id())
else:
return VariantClassification(VariantClassification.RNA, variant_type, tx.get_transcript_id())
if ref_allele == "-":
ref_allele = ""
if alt_allele == "-":
alt_allele = ""
s = int(start)
e = int(end)
is_exon_overlap = TranscriptProviderUtils.determine_if_exon_overlap(s, e, tx, variant_type)
is_splice_site_tuple = self._determine_if_splice_site_overlap(s, e, tx, variant_type, dist)
is_splice_site = is_splice_site_tuple[0]
is_beyond_exons, side, is_flank = self._determine_beyond_exon_info_vt(start, end, tx, variant_type)
if not is_exon_overlap and not is_beyond_exons:
exon_i = TranscriptProviderUtils.determine_closest_exon(tx, int(start), int(end))
if is_splice_site:
# Intron Splice Site
return VariantClassification(VariantClassification.SPLICE_SITE, variant_type, tx.get_transcript_id(), vc_secondary=VariantClassification.INTRON, exon_i=exon_i)
else:
return VariantClassification(VariantClassification.INTRON, variant_type, tx.get_transcript_id(), exon_i=exon_i)
if not is_exon_overlap and is_beyond_exons:
if is_flank:
# Flanks
if side.startswith("3"):
return VariantClassification(VariantClassification.THREE_PRIME_PRIME_FLANK, variant_type, transcript_id=tx.get_transcript_id())
else:
return VariantClassification(VariantClassification.FIVE_PRIME_PRIME_FLANK, variant_type, transcript_id=tx.get_transcript_id())
else:
# IGR
return VariantClassification(VariantClassification.IGR, variant_type)
is_start_codon_overlap = self._determine_codon_overlap(s, e, tx.get_start_codon(), variant_type)
is_stop_codon_overlap = self._determine_codon_overlap(s, e, tx.get_stop_codon(), variant_type)
if is_start_codon_overlap and not variant_type.endswith("NP"):
return VariantClassification('Start_Codon_' + variant_type.capitalize(), variant_type, transcript_id=tx.get_transcript_id())
if is_stop_codon_overlap and not variant_type.endswith("NP"):
return VariantClassification('Stop_Codon_' + variant_type.capitalize(), variant_type, transcript_id=tx.get_transcript_id())
is_cds_overlap = self._determine_if_cds_overlap(s, e, tx, variant_type)
if is_exon_overlap and not is_cds_overlap and not is_start_codon_overlap and not is_stop_codon_overlap:
# UTR
if side.startswith("3"):
vc_tmp = VariantClassification.THREE_PRIME_UTR
else:
vc_tmp = VariantClassification.FIVE_PRIME_UTR
transcript_position_exon_space_start, transcript_position_exon_space_end = TranscriptProviderUtils.convert_genomic_space_to_exon_space(start, end, tx)
vc = self._determine_de_novo(vc_tmp, transcript_position_exon_space_start, ref_allele, alt_allele, tx, variant_type)
return VariantClassification(vc, variant_type, transcript_id=tx.get_transcript_id(), )
# We have a clean overlap in the CDS. Includes start codon or stop codon.
if is_cds_overlap or is_stop_codon_overlap or is_start_codon_overlap:
is_frameshift_indel = self.is_frameshift_indel(variant_type, int(start), int(end), alt_allele)
return self._determine_vc_for_cds_overlap(start, end, ref_allele, alt_allele, is_frameshift_indel, is_splice_site, tx, variant_type, is_start_codon_overlap)
raise ValueError("Could not determine variant classification: " + tx.get_trancript_id() + " " + str([ref_allele, alt_allele, start, end]))
def variant_classify(self,
tx,
ref_allele,
alt_allele,
start,
end,
variant_type,
dist=2):
"""Perform classifications.
Everything handled in genomic space
*RNA*
x'UTR
Splice_Site (Intron)
Intron
Splice_Site (Exon)
{Missense, Silent}
{Nonsense, Silent}
{Nonstop, Silent}
IGR
x'Flank
De_novo_Start
"""
gene_type = tx.get_gene_type()
if gene_type != "protein_coding":
if gene_type == VariantClassification.LINCRNA:
return VariantClassification(VariantClassification.LINCRNA,
variant_type,
tx.get_transcript_id())
else:
return VariantClassification(VariantClassification.RNA,
variant_type,
tx.get_transcript_id())
if ref_allele == "-":
ref_allele = ""
if alt_allele == "-":
alt_allele = ""
s = int(start)
e = int(end)
is_exon_overlap = TranscriptProviderUtils.determine_if_exon_overlap(
s, e, tx, variant_type)
is_splice_site_tuple = self._determine_if_splice_site_overlap(
s, e, tx, variant_type, dist)
is_splice_site = is_splice_site_tuple[0]
is_beyond_exons, side, is_flank = self._determine_beyond_exon_info_vt(
start, end, tx, variant_type)
if not is_exon_overlap and not is_beyond_exons:
exon_i = TranscriptProviderUtils.determine_closest_exon(
tx, int(start), int(end))
if is_splice_site:
# Intron Splice Site
return VariantClassification(
VariantClassification.SPLICE_SITE,
variant_type,
tx.get_transcript_id(),
vc_secondary=VariantClassification.INTRON,
exon_i=exon_i)
else:
return VariantClassification(VariantClassification.INTRON,
variant_type,
tx.get_transcript_id(),
exon_i=exon_i)
if not is_exon_overlap and is_beyond_exons:
if is_flank:
# Flanks
if side.startswith("3"):
return VariantClassification(
VariantClassification.THREE_PRIME_PRIME_FLANK,
variant_type,
transcript_id=tx.get_transcript_id())
else:
return VariantClassification(
VariantClassification.FIVE_PRIME_PRIME_FLANK,
variant_type,
transcript_id=tx.get_transcript_id())
else:
# IGR
return VariantClassification(VariantClassification.IGR,
variant_type)
is_start_codon_overlap = self._determine_codon_overlap(
s, e, tx.get_start_codon(), variant_type)
is_stop_codon_overlap = self._determine_codon_overlap(
s, e, tx.get_stop_codon(), variant_type)
if is_start_codon_overlap and not variant_type.endswith("NP"):
return VariantClassification('Start_Codon_' +
variant_type.capitalize(),
variant_type,
transcript_id=tx.get_transcript_id())
if is_stop_codon_overlap and not variant_type.endswith("NP"):
return VariantClassification('Stop_Codon_' +
variant_type.capitalize(),
variant_type,
transcript_id=tx.get_transcript_id())
is_cds_overlap = self._determine_if_cds_overlap(s, e, tx, variant_type)
if is_exon_overlap and not is_cds_overlap and not is_start_codon_overlap and not is_stop_codon_overlap:
# UTR
if side.startswith("3"):
vc_tmp = VariantClassification.THREE_PRIME_UTR
else:
vc_tmp = VariantClassification.FIVE_PRIME_UTR
transcript_position_exon_space_start, transcript_position_exon_space_end = TranscriptProviderUtils.convert_genomic_space_to_exon_space(
start, end, tx)
vc = self._determine_de_novo(vc_tmp,
transcript_position_exon_space_start,
ref_allele, alt_allele, tx,
variant_type)
return VariantClassification(
vc,
variant_type,
transcript_id=tx.get_transcript_id(),
)
# We have a clean overlap in the CDS. Includes start codon or stop codon.
if is_cds_overlap or is_stop_codon_overlap or is_start_codon_overlap:
is_frameshift_indel = self.is_frameshift_indel(
variant_type, int(start), int(end), alt_allele)
return self._determine_vc_for_cds_overlap(
start, end, ref_allele, alt_allele, is_frameshift_indel,
is_splice_site, tx, variant_type, is_start_codon_overlap)
raise ValueError("Could not determine variant classification: " +
tx.get_trancript_id() + " " +
str([ref_allele, alt_allele, start, end]))
