Reconstructing viral haplotypes using long reads

Motivation: Most RNA viruses lack strict proofreading during replication. Coupled with a high replication rate, some RNA viruses can form a virus population containing a group of genetically related but different haplotypes. Characterizing the haplotype composition in a virus population is thus important to understand viruses' evolution. Many attempts have been made to reconstruct viral haplotypes using next-generation sequencing (NGS) reads. However, the short length of NGS reads cannot cover distant single-nucleotide variants, making it difficult to reconstruct complete or near-complete haplotypes. Given the fast developments of third-generation sequencing technologies, a new opportunity has arisen for reconstructing full-length haplotypes with long reads.

Results: In this work, we developed a new tool, RVHaplo to reconstruct haplotypes for known viruses from long reads. We tested it rigorously on both simulated and real viral sequencing data and compared it against other popular haplotype reconstruction tools. The results demonstrated that RVHaplo outperforms the state-of-the-art tools for viral haplotype reconstruction from long reads. Especially, RVHaplo can reconstruct the rare (1% abundance) haplotypes that other tools usually missed.