VCF file generated by Gridss not recognised by VEP

Question

[Reda]

Hello,

Currently, I am engaged in analyzing genomic Next-Generation Sequencing (NGS) data as a part of my professional activities. Specifically, I am attempting to integrate the Gridss tool into my workflow for the purpose of variant calling (indels). Unfortunately, I have encountered an issue with the output format, as the Variant Call Format (VCF) generated by Gridss is not recognized by the Variant Effect Predictor (VEP) or Cancer-Related Analysis of Variants Toolkit (Cravat) tools. These two tools are commonly employed in my laboratory for the annotation of genetic variants.

Therefore, I am seeking a viable solution for reformatting the Gridss-generated VCF into a format that can be recognized by the aforementioned annotators.

Sincerely.

[Pierre Lindenbaum]

please, show us an example of VCF line generated by gridss and show us the VEP error message.

[Reda]

Hi, many thanks for this return, here a few lines from Gridss's VCF file. TH e error meesage displayed by VEP is: the input format is invalid or not recognized...

##fileformat=VCFv4.2
##FILTER=<ID=PASS,Description="All filters passed">
##FILTER=<ID=ASSEMBLY_BIAS,Description="Mismatch between number of directly supporting reads and reads supporting via assembly.">
##FILTER=<ID=ASSEMBLY_ONLY,Description="Variant is supported only by assembly evidence.">
##FILTER=<ID=ASSEMBLY_TOO_FEW_READ,Description="Not enough reads contribute to this assembly as specified by 'assembly.minReads'">
##FILTER=<ID=ASSEMBLY_TOO_SHORT,Description="This assembly is shorter than a read length">
##FILTER=<ID=INSUFFICIENT_SUPPORT,Description="Does not reach the required threshold quality for calling as specified by 'variantcalling.minScore'">
##FILTER=<ID=LOW_MAPQ,Description="Mapping location may be ambiguous.">
##FILTER=<ID=LOW_QUAL,Description="Low quality call as specified by 'variantcalling.lowQuality'">
##FILTER=<ID=NO_ASSEMBLY,Description="No assembly supporting this variant could be found.">
##FILTER=<ID=NO_RP,Description="Variant does not have any direct read pair support.">
##FILTER=<ID=NO_SR,Description="Variant does not have any direct split read support.">
##FILTER=<ID=REF,Description="Breakpoint corresponds to reference allele">
##FILTER=<ID=SINGLE_ASSEMBLY,Description="Only one side of the breakpoint could be assembled.">
##FILTER=<ID=SINGLE_SUPPORT,Description="Supported by fewer than 'variantcalling.minReads' fragments">
##FILTER=<ID=SMALL_EVENT,Description="Event size is smaller than the minimum reportable size specified by 'variantcalling.minSize'">
##FORMAT=<ID=AF,Number=A,Type=Float,Description="Allele fraction">
##FORMAT=<ID=ANRP,Number=1,Type=Integer,Description="Count of read pairs at this breakend assembled into a contig that does not support the breakpoint.">
##FORMAT=<ID=ANRPQ,Number=1,Type=Float,Description="Quality score of read pairs at this breakend assembled into a contig that does not support the breakpoint.">
##FORMAT=<ID=ANSR,Number=1,Type=Integer,Description="Count of split reads at this breakend assembled into a contig that does not support the breakpoint.">
##FORMAT=<ID=ANSRQ,Number=1,Type=Float,Description="Quality score of split reads at this breakend assembled into a contig that does not support the breakpoint.">
.....

#CHROM  POS ID  REF ALT QUAL    FILTER  INFO    FORMAT  100_C2_1000
chr1    1041638 gridss0fb_5o    C   C[chr6:135200148[   98.02   LOW_QUAL;NO_ASSEMBLY    ANRP=0;ANRPQ=0;ANSR=0;ANSRQ=0;AS=0;ASC=2X;ASQ=0;ASRP=0;ASSR=0;BA=0;BAQ=0;BASRP=0;BASSR=0;BQ=0;BSC=0;BSCQ=0;BUM=0;BUMQ=0;BVF=0;CAS=0;CASQ=0;CIPOS=0,1;CIRPOS=0,1;CQ=98.02;EVENT=gridss0fb_5;HOMLEN=1;HOMSEQ=C;IC=0;IHOMPOS=0,1;IQ=0;MATEID=gridss0fb_5h;MQ=60;MQN=60;MQX=60;RAS=0;RASQ=0;REF=0;REFPAIR=0;RP=0;RPQ=0;SB=0.5;SC=103M2X;SR=4;SRQ=98.02;SVTYPE=BND;VF=2  AF:ANRP:ANRPQ:ANSR:ANSRQ:ASQ:ASRP:ASSR:BAQ:BASRP:BASSR:BQ:BSC:BSCQ:BUM:BUMQ:BVF:CASQ:IC:IQ:QUAL:RASQ:REF:REFPAIR:RP:RPQ:SR:SRQ:VF   1:0:0:0:0:0:0:0:0:0:0:0:0:0:0:0:0:0:0:0:98.02:0:0:0:0:0:4:98.02:2

[Ryangguk Kim]

Do you need proper annotation of that structural variant or want to just ignore it so that other non-structural variants can be processed?

Answer 1

[Pierre Lindenbaum]

VEP doesn't support variants in BND format: https://www.ensembl.org/info/docs/tools/vep/vep_formats.html#sv , https://github.com/Ensembl/ensembl-vep/issues/782

Answer 2

[Sunnywy0808]

https://github.com/PapenfussLab/gridss/pull/618 hope it is helpful to you