A hepatitis B virus (HBV) sequence variation graph improves alignment and sample-specific consensus sequence construction.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Hepatitis B virus*/genetics ; Genome, Viral* ; Consensus Sequence*/genetics; Humans ; Phylogeny ; Sequence Alignment/methods ; Genetic Variation ; Hepatitis B, Chronic/virology ; DNA, Viral/genetics ; Sequence Analysis, DNA/methods

Nearly 300 million individuals live with chronic hepatitis B virus (HBV) infection (CHB), for which no curative therapy is available. As viral diversity is associated with pathogenesis and immunological control of infection, improved methods to characterize this diversity could aid drug development efforts. Conventionally, viral sequencing data are mapped/aligned to a reference genome, and only the aligned sequences are retained for analysis. Thus, reference selection is critical, yet selecting the most representative reference a priori remains difficult. We investigate an alternative pangenome approach which can combine multiple reference sequences into a graph which can be used during alignment. Using simulated short-read sequencing data generated from publicly available HBV genomes and real sequencing data from an individual living with CHB, we demonstrate alignment to a phylogenetically representative 'genome graph' can improve alignment, avoid issues of reference ambiguity, and facilitate the construction of sample-specific consensus sequences more genetically similar to the individual's infection. Graph-based methods can, therefore, improve efforts to characterize the genetics of viral pathogens, including HBV, and have broader implications in host-pathogen research.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Duchen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Update of: bioRxiv. 2023 Jan 12:2023.01.11.523611. doi: 10.1101/2023.01.11.523611. (PMID: 36711598)

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United Kingdom WT_ Wellcome Trust; DP2 DA056130 United States DA NIDA NIH HHS; R01 AI148049 United States AI NIAID NIH HHS; R35 HG011944 United States HG NHGRI NIH HHS

0 (DNA, Viral)

Date Created: 20240426 Date Completed: 20240426 Latest Revision: 20241211

20241211

PMC11051683

10.1371/journal.pone.0301069

38669259