A spectrum of free software tools for processing the VCF variant call format: vcflib, bio-vcf, cyvcf2, hts-nim and slivar

Author summaryMost bioinformatics workflows deal with DNA/RNA variations that are typically represented in the variant call format (VCF)-a file format that describes mutations (SNP and MNP), insertions and deletions (INDEL) against a reference genome. Here we present a wide range of free and open source software tools that are used in biomedical sequencing workflows around the world today. Since its introduction in 2011 the variant call format (VCF) has been widely adopted for processing DNA and RNA variants in practically all population studies-as well as in somatic and germline mutation studies. The VCF format can represent single nucleotide variants, multi-nucleotide variants, insertions and deletions, and simple structural variants called and anchored against a reference genome.Here we present a spectrum of over 125 useful, complimentary free and open source software tools and libraries, we wrote and made available through the multiple vcflib, bio-vcf, cyvcf2, hts-nim and slivar projects. These tools are applied for comparison, filtering, normalisation, smoothing and annotation of VCF, as well as output of statistics, visualisation, and transformations of files variants. These tools run everyday in critical biomedical pipelines and countless shell scripts. Our tools are part of the wider bioinformatics ecosystem and we highlight best practices.We shortly discuss the design of VCF, lessons learnt, and how we can address more complex variation through pangenome graph formats, variation that can not easily be represented by the VCF format.

Automated summary

The author presents a range of free and open source software tools used in biomedical sequencing workflows for DNA/RNA variations. The importance of the variant call format (VCF) is highlighted, and the article discusses how to handle more complex variations.