Journal Article

Towards pan-genome read alignment to improve variation calling

Norri, Tuukka, Välimäki, Niko, Pitkänen, Esa, Mäkinen, Veli, Valenzuela, Daniel

2018

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Access to Information / Analysis / Animal Genetics and Genomics / Biomedical and Life Sciences / Genetic algorithms / Genetic Variation / Genome, Human / Genomics / Genotype / Humans / Internet / Life Sciences / Microarrays / Microbial Genetics and Genomics / Pan-genome reference / Plant Genetics and Genomics / Proteomics / Read alignment / Sequence Alignment / Sequence Analysis, DNA - methods / Software / Variation calling / Workflow