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Description
In evaluating glnexus for merging a single sample, glnexus is missing calls where the gVCF call overlaps a Refcall record with a null (./
) genotype. The variant calls are correct so is there an option I can add to preserve these calls?
Observed this mostly in INDELs, but there are some SNVs too. Two examples are below with the attached files here - workspace.tar.gz
INDEL
Expecting a HOM ALT, but no call is emitted from glnexus if the overlapping REF call is present
$ grep -A 2 "#CHROM" indel*.vcf
indel_call.g.vcf:#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT NA24385
indel_call.g.vcf-chr1 7655595 . TAC T,<*> 26.1 PASS . GT:GQ:DP:AD:VAF:PL 1/1:20:18:3,15,0:0.833333,0:26,21,0,990,990,990
--
indel_merge.g.vcf:#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT NA24385
indel_merge.g.vcf-chr1 7655595 . TAC T,<*> 26.1 PASS . GT:GQ:DP:AD:VAF:PL 1/1:20:18:3,15,0:0.833333,0:26,21,0,990,990,990
indel_merge.g.vcf-chr1 7655597 . C T,<*> 0.1 RefCall . GT:GQ:DP:AD:VAF:PL ./.:15:3:1,2,0:0.666667,0:0,14,31,990,990,990
$ glnexus_cli --config DeepVariant_unfiltered indel_merge.g.vcf 2> /dev/null | bcftools view - -H
$ rm -rf GLnexus.DB/
$ glnexus_cli --config DeepVariant_unfiltered indel_call.g.vcf 2> /dev/null | bcftools view - -H
chr1 7655595 chr1_7655595_TAC_T TAC T 26 . AF=1;AQ=26 GT:DP:AD:GQ:PL:RNC 1/1:18:3,15:20:26,21,0:..
SNV
Same issue as before - running glnexus on the g.vcf with the overlapping null/RefCall does not output the expected call
$ grep -A 2 "#CHROM" snp_*.vcf
snp_call.g.vcf:#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT NA24385
snp_call.g.vcf-chr3 103921462 . A T,<*> 48.2 PASS . GT:GQ:DP:AD:VAF:PL 1/1:27:26:0,26,0:1,0:48,26,0,990,990,990
--
snp_merge.g.vcf:#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT NA24385
snp_merge.g.vcf-chr3 103921461 . TA T,<*> 0.3 RefCall . GT:GQ:DP:AD:VAF:PL ./.:12:28:26,2,0:0.0714286,0:0,11,40,990,990,990
snp_merge.g.vcf-chr3 103921462 . A T,<*> 48.2 PASS . GT:GQ:DP:AD:VAF:PL 1/1:27:26:0,26,0:1,0:48,26,0,990,990,990
$ glnexus_cli --config DeepVariant_unfiltered snp_call.g.vcf 2> /dev/null | bcftools view - -H
chr3 103921462 chr3_103921462_A_T A T 48 . AF=1;AQ=48 GT:DP:AD:GQ:PL:RNC 1/1:26:0,26:27:48,26,0:..
$ rm -rf GLnexus.DB/
$ glnexus_cli --config DeepVariant_unfiltered snp_merge.g.vcf 2> /dev/null | bcftools view - -H
$
I've played around with other configs, but the closest to the desired behavior of outputting the variant is with a modified YAML based on DeepVariant_unfiltered
with just the additional option trim_uncalled_alleles: false
(in custom.yml
in attached). However, the result is still unexpected because the records have a null genotype like below -
#CHROM POS ID REF ALT QUAL FILTER INFO FORMAT NA24385
chr1 7655595 chr1_7655595_TAC_T TAC T 26 . AF=1;AQ=26 GT:DP:AD:GQ:PL:RNC ./.:3:.:.:0,0,0:OO
Thank you for the any help and supporting this useful tool!