table_annovar vs annotate_variation output

[sup3rgiu]

Hi.

I'm using this sample file as input (let's call it to_annotate.avinput):

3	15295364	15295364	G	A

annotate_variation.pl

When I use annotate_variation:

perl $ANNOVAR_DIR/annotate_variation.pl \
		to_annotate.avinput $ANNOVAR_DIR/humandb/ \
		-build hg19 \
		-out output \
		--geneanno -dbtype refGene

the output is the following:

upstream;downstream	SH3BP5-AS1(dist=327);CAPN7,SH3BP5(dist=327)	3	15295364	15295364	G	A

table_annovar.pl

While when I use table_annovar:

perl $ANNOVAR_DIR/table_annovar.pl \
		to_annotate.avinput $ANNOVAR_DIR/humandb/ \
		-buildver hg19 \
		-out output  \
		-remove \
		-protocol refGene \
		-operation g \
		-nastring .	

the output is the following:

Chr	Start	End	Ref	Alt	Func.refGene	Gene.refGene	GeneDetail.refGene	ExonicFunc.refGene	AAChange.refGene
3	15295364	15295364	G	A	upstream;downstream	SH3BP5-AS1;CAPN7;SH3BP5	dist=327;dist=327	.	.

Issue

The issue is that when

• annotate_variation is used, genes are separated by both , and ; --> SH3BP5-AS1(dist=327);CAPN7,SH3BP5(dist=327)
• table_annovar is used, genes are separated only by ; --> SH3BP5-AS1;CAPN7;SH3BP5

This prevents me to correctly assign the genes to the functions when using table_annovar (that is the recommended command to use)

[kaichop]

This is a problem with table_annovar; it did not handle "CAPN7,SH3BP5(dist=327)" correctly. I will see how to address this issue.

…

On Tue, Dec 17, 2024 at 11:45 AM SUPERGIU ***@***.***> wrote: Hi. I'm using this sample file as input (let's call it to_annotate.avinput): 3 15295364 15295364 G A annotate_variation.pl When I use annotate_variation: perl $ANNOVAR_DIR/annotate_variation.pl \ to_annotate.avinput $ANNOVAR_DIR/humandb/ \ -build hg19 \ -out output \ --geneanno -dbtype refGene the output is the following: upstream;downstream SH3BP5-AS1(dist=327);CAPN7,SH3BP5(dist=327) 3 15295364 15295364 G A table_annovar.pl While when I use table_annovar: perl $ANNOVAR_DIR/table_annovar.pl \ to_annotate.avinput $ANNOVAR_DIR/humandb/ \ -buildver hg19 \ -out output \ -remove \ -protocol refGene \ -operation g \ -nastring . the output is the following: Chr Start End Ref Alt Func.refGene Gene.refGene GeneDetail.refGene ExonicFunc.refGene AAChange.refGene 3 15295364 15295364 G A upstream;downstream SH3BP5-AS1;CAPN7;SH3BP5 dist=327;dist=327 . . Issue The issue is that when - annotate_variation is used, genes are separated by both , and ; --> SH3BP5-AS1(dist=327);CAPN7,SH3BP5(dist=327) - table_annovar is used, genes are separated only by ; --> SH3BP5-AS1;CAPN7;SH3BP5 This prevents me to correctly assign the genes to the functions when using table_annovar (that is the recommended command to use) — Reply to this email directly, view it on GitHub <#269>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/ABNG3OHJSP42BK2RYA7ZIUD2GBIKFAVCNFSM6AAAAABTY2W2QGVHI2DSMVQWIX3LMV43ASLTON2WKOZSG42DKNBVHA4DQMI> . You are receiving this because you are subscribed to this thread.Message ID: ***@***.***>

[sup3rgiu]

@kaichop thanks a lot! Let me know if you need some help with testing 🙂

[sup3rgiu]

I've looked at the code.

Inside the geneOperation() function of the table_annovar.pl file, we have (line 508 of revision c66762679205bdc00c64e465ac6ccd8f62132e2f, date 2020-06-08 00:46:07 -0400 (Mon, 8 Jun 2020)):

while (<FUNCTION>)
{
	s/[\r\n]+$//;
	m/^([^\t]+)\t([^\t]+)\t(\S+\s+\S+\s+\S+\s+\S+\s+\S+).*/ or die "Error: invalid record found in annovar outputfile: <$_>\n";		#example: splicing        KLK12(NM_019598:exon4:c.457+6T>C,NM_145894:exon4:c.457+6T>C,NM_001370125:exon4:c.457+6T>C)
	my ($function, $gene, $varstring) = ($1, $2, $3);
	my $spliceanno = '';
	$varstring =~ s/\s+/\t/g;
	while ($gene =~ m/\(([^)]+)\)/g) {
		$spliceanno .= "$1;";
	}
	chop $spliceanno if $gene =~ s/\(([^)]+)\)//g;
	$spliceanno =~ tr/,/;/;
	$gene =~ tr/,/;/;

The problem seems to be easily solved by commenting out the last line:

$gene =~ tr/,/;/;

This works for my purposes, but I don't know if it breaks anything else.

However, there is a similar problem for the GeneDetail column, since:

• annotate_variation: SH3BP5-AS1(dist=327);CAPN7,SH3BP5(dist=327)
• table_annovar: dist=327;dist=327

So, using table_annovar I don't know to which gene the dist refers to.
This is due the while loop:

while ($gene =~ m/\(([^)]+)\)/g) {
    $spliceanno .= "$1;";
}

but this time a fix should be based on some formatting logic.
A possible solution would be to add an empty value for genes without details:
dist=327;;dist=327 (note the double ;; as we have no detail for the middle gene CAPN7).