Towards pan-genome read alignment to improve variation calling.
BACKGROUND
Typical human genome differs from the reference genome at 4-5 million sites. This diversity is increasingly catalogued in repositories such as ExAC/gnomAD, consisting of >15,000 whole-genomes and >126,000 exome sequences from different individuals. Despite this enormous diversity, resequencing data workflows are still based on a single human reference genome. Identification and genotyping of genetic variants is typically carried out on short-read data aligned to a single reference, disregarding the underlying variation.


RESULTS
We propose a new unified framework for variant calling with short-read data utilizing a representation of human genetic variation - a pan-genomic reference. We provide a modular pipeline that can be seamlessly incorporated into existing sequencing data analysis workflows. Our tool is open source and available online: https://gitlab.com/dvalenzu/PanVC .


CONCLUSIONS
Our experiments show that by replacing a standard human reference with a pan-genomic one we achieve an improvement in single-nucleotide variant calling accuracy and in short indel calling accuracy over the widely adopted Genome Analysis Toolkit (GATK) in difficult genomic regions.
['Valenzuela|Daniel|D|', 'Norri|Tuukka|T|', 'Välimäki|Niko|N|', 'Pitkänen|Esa|E|', 'Mäkinen|Veli|V|']
D022126:Access to Information D014644:Genetic Variation D015894:Genome, Human D006801:Humans D020407:Internet D016415:Sequence Alignment D017422:Sequence Analysis, DNA D012984:Software D057188:Workflow
Read alignment Variation calling Pan-genome reference