AccuVIR: an ACCUrate VIRal genome assembly tool for third-generation sequencing data

Motivation: RNA viruses tend to mutate constantly. While many of the variants are neutral, some can lead to higher transmissibility or virulence. Accurate assembly of complete viral genomes enables identification of underlying variants, which are essential for studying virus evolution and elucidating the relationship between genotypes and virus properties. Recently, third-generation sequencing platforms such as Nanopore sequencers have been used for real-time virus sequencing for Ebola, Zika, COVID-19, etc. However, their high per-base error rate prevents accurate reconstruction of the viral genome. Results: In this work, we introduce a new tool, AccuVIR, for viral genome assembly and polishing using error-prone long reads. It can better distinguish sequencing errors from true variants based on the key observation that sequencing errors can disrupt the gene structures of viruses, which usually have high density of coding regions. Our experimental results on both simulated and real third-generation sequencing data demonstrated its superior performance on generating more accurate viral genomes than generic assembly or polish tools.