基因注释软件-VEP

在使用VEP软件进行功能注释阶段，其实会发现存在部分注释结果和整体注释逻辑存在偏差。由于不清楚是认识的不足还是VEP本身代码存在Bug。因此对VEP的源码进行溯源核查。

Chr	Start	End	Ref	Alt	Gene	Trans	cHGVS	pHGVS
chr12	122064779	122064785	ACCGCCA	C	ORAI1	NM_032790.3	c.132_138delinsC	-

Chr	Start	End	Ref	Alt	Gene	Trans	cHGVS	pHGVS
chr1	10342506	10342555	TCAGGTGGGCTTGACGTCTGTGACCAGTATTCAAGAGAGGATCATGTCTA	CCAGGTGTAGACATGATCCTCTCTTGAATACTGGTCACAGACGTCAAGCC	KIF1B	NM_015074.3	c.1211_1260delinsCCAGGTGTAGACATGATCCTCTCTTGAATACTGGTCACAGACGTCAAGCC	p.I404_L420delinsTRCRHDPLLNTGHRRQA

源码重点部分记录

VEP输出结果整体记录在 “ modules\Bio\EnsEMBL\VEP\OutputFactory.pm ” 中，如果是处于核查可以基于该模块进行反向溯源；
预测氨基酸变化
代码在 “modules\Bio\EnsEMBL\Variation\TranscriptVariationAllele.pm” Line:684

=head2 peptide
  Description: Return the amino acid sequence that this allele is predicted to result in
  Returntype : string or undef if this allele is not in the CDS or is a frameshift
  Exceptions : none
  Status     : Stable
=cut

对输入文件进行解析校验
modules\Bio\EnsEMBL\VEP\Parser.pm

=head2 validate_vf
  Arg 1      : Bio::EnsEMBL::Variation::BaseVariationFeature
  Example    : $is_valid = $parser->validate_vf($vf);
  Description: Performs various (configurable) checks on a VariationFeature
               as produced by the parser:
                - creates a variation_name from the location+alleles if none
                - checks if chr is in user-specified list if provided
                - checks start and end look like numbers
                - checks start/end are valid (start <= end + 1) and corresponds to ref allele
                - checks chr is in valid list
                - checks ref allele vs genome if requested
  Returntype : bool
  Exceptions : none
  Caller     : next()
  Status     : Stable
=cut

HGVS信息注释
获取变异最接近的转录本
modules\Bio\EnsEMBL\VEP\AnnotationType\Transcript.pm

 =head2 get_nearest
  Arg 1      : Bio::EnsEMBL::Variation::BaseVariationFeature $vf
  Arg 2      : string $type (transcript, gene or symbol)
  Example    : $nearest_gene = $as->get_nearest($vf, 'symbol');
  Description: Gets ID (one of transcript, gene, symbol) of the nearest
               transcript to the given variant.
  Returntype : string
  Exceptions : none
  Caller     : annotate_InputBuffer()
  Status     : Stable
=cut

对应代码： modules\Bio\EnsEMBL\Variation\TranscriptVariation.pm

sub _hgvs_generic {
    my $self = shift;
    my $reference = pop;
    my $hgvs = shift;
    #The rna and mitochondrial modes have not yet been implemented, so return undef in case we get a call to these
    return undef if ($reference =~ m/rna|mitochondrial/);
    # The HGVS subroutine
    my $sub = qq{hgvs_$reference};
    # Loop over the TranscriptVariationAllele objects associated with this TranscriptVariation
    foreach my $tv_allele (@{ $self->get_all_alternate_TranscriptVariationAlleles }) {
        #If an HGVS hash was supplied and the allele exists as key, set the HGVS notation for this allele
        if (defined($hgvs)) {
            my $notation = $hgvs->{$tv_allele->variation_feature_seq()};
            $tv_allele->$sub($notation) if defined $notation;
        }
        # Else, add the HGVS notation for this allele to the HGVS hash
        else {
	    $hgvs->{$tv_allele->variation_feature_seq()} = $tv_allele->$sub();
        }
    }
    return $hgvs;
}

modules\Bio\EnsEMBL\VEP\VariantRecoder.pm

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源码重点部分记录