Merge sniffles2 VCF files from multiple samples failed with "The REF prefixes differ"

[liuyang2006]

I want to merge all samples's VCF together into multi-sample VCF, but failed. All VCF files are processed using same genome reference.

Command:

bcftools merge --force-samples -O z -o sniffles2_aml_all_patient_data_merge_output.vcf.gz GT23-09911_sniffles2_output.vcf.gz GT23-09912_sniffles2_output.vcf.gz GT23-09913_sniffles2_output.vcf.gz GT23-09914_sniffles2_output.vcf.gz GT23-09915_sniffles2_output.vcf.gz GT23-09916_sniffles2_output.vcf.gz GT23-09917_sniffles2_output.vcf.gz GT23-09918_sniffles2_output.vcf.gz GT23-09919_sniffles2_output.vcf.gz GT23-09920_sniffles2_output.vcf.gz GT23-09923_sniffles2_output.vcf.gz

Error:

The REF prefixes differ: tgtggccagcaggcggcgctgcaggagaggagatgcCCAGGCCAGGCGGCCGGCGCACGCGggttctc vs N (68,1)
Failed to merge alleles at chr1:36452 in GT23-09918_sniffles2_output.vcf.gz

[lfpaulin]

If using Sniffles I recommend using the merge mode of sniffles to perform the same task
For that the SNF files will be needed.

For that particular error, were all SV calls made with the same reference genome version, i.e GRCh38 p13 vs p14, or some file was called without reference, thus the DEL calls are only symbolic

[liuyang2006]

Dear author,

I am using same reference genome, but when I merge them failed for VCF file.

I also generate .snf file, but could you guide me how to merge .snf file? Thank you!

[fritzsedlazeck]

So we typically use the .snf files per sample to do the merge. The issue is that bcftools works great for SNP but not for SV.

When you have the .snf files you wanna do something like this:
sniffles --input sample1.snf sample2.snf ... sampleN.snf --vcf multisample.vcf

hope that helps
Fritz