Single-virion sequencing of lamivudine-treated HBV populations reveal population evolution dynamics and demographic history

BMC Genomics
Yuan O ZhuMartin Hibberd

Abstract

Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients - once before antiviral treatment and once after viral rebound due to resistance. With single-virion sequencing, we obtained 248-8796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified fo...Continue Reading

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Citations

Apr 22, 2021·Expert Review of Molecular Diagnostics·Selene Garcia-GarciaFrancisco Rodríguez-Frías

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Methods Mentioned

BETA
PCR
electrophoresis

Software Mentioned

LoFreq
RS
ReadsOfInsert
BAsE
Trimmomatic
BEAST
FastTree
MEM
GATK
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