How do I merge VCFs files containing CNVs?
vcf-merge (or better:
bcftools merge) does a column-based merge of VCF files, basically taking on an additional genotype column to each variant. While this sort-of works, it doesn't take into account all the information about variation. There might be low coverage at a region in one VCF file that indicates a deletion, but the deletion is only observable when considering other samples with high coverage at that same region. It's also possible that INDELs could be defined differently in different samples, requiring an additional
bcftools norm step for left-normalisation prior to the merge.
Assuming this column-based merge is what you want (and if not, then
bcftools concat is your friend for row-based merging), then it's better to regenerate the merged VCF file as a multi-column file directly. One way of doing this is feeding all BAM files into
samtools mpileup to generate genotype likelihoods, then feeding the result of that into
bcftools call. Something like the following:
samtools mpileup -uf ref.fa in1.bam in2.bam in3.bam | \ bcftools call -mv -O z -o variants_ref_1-3.vcf.gz