Approaches to Studying Virus Pangenome Variation Graphs

Pangenome variation graphs (PVGs) allow for the representation of genetic diversity in a more nuanced way than traditional reference-based approaches. Here I focus on how PVGs are a powerful tool for studying genetic variation in viruses, offering insights into the complexities of viral quasispecies, mutation rates, and population dynamics. PVGs originated in human genomics and hold great promise for viral genomics. Previous work has been constrained by small sample sizes and gene-centric methods, whereas PVGs enable a more comprehensive approach to studying viral diversity. Large viral genome collections should be used to make PVGs, which offer significant advantages. Here, I outline accessible tools to achieve their construction. This spans PVG construction, PVG file formats, PVG manipulation and analysis, PVG visualisation, measuring PVG openness, and mapping reads to PVGs. Additionally, the development of PVG-specific formats for mutation representation and personalised PVGs that reflect specific research questions will further enhance PVG applications. Challenges remain, particularly in managing nested variants, optimising error detection, optimising k-mer/minimizer-based approaches for AT-rich genomes, incorporating long read sequencing data, and scalable visualisation approaches. Nevertheless, PVGs offer a new opportunity for viral population genomics, and a testing ground for tool development prior to application to larger eukaryotic genomes. These advances will enable more accurate and comprehensive detection of viral mutations, contributing to a deeper understanding of viral evolution and genotype-phenotype associations.