title: Next-generation sequencing reveals large connected networks of intra-host HCV variants.
abstract: BACKGROUND
  Next-generation sequencing (NGS) allows for sampling numerous viral variants from infected patients. This provides a novel opportunity to represent and study the mutational landscape of Hepatitis C Virus (HCV) within a single host.
  
  
  RESULTS
  Intra-host variants of the HCV E1/E2 region were extensively sampled from 58 chronically infected patients. After NGS error correction, the average number of reads and variants obtained from each sample were 3202 and 464, respectively. The distance between each pair of variants was calculated and networks were created for each patient, where each node is a variant and two nodes are connected by a link if the nucleotide distance between them is 1. The work focused on large components having > 5% of all reads, which in average account for 93.7% of all reads found in a patient.
  
  
  CONCLUSIONS
  Most intra-host variants are organized into distinct single-mutation components that are: well separated from each other, represent genetic distances between viral variants, robust to sampling, reproducible and likely seeded during transmission events. Facilitated by NGS, large components offer a novel evolutionary framework for genetic analysis of intra-host viral populations and understanding transmission, immune escape and drug resistance.
authors.forename: David S
authors.initials: DS
authors.lastname: Campo
authors.forename: Zoya
authors.initials: Z
authors.lastname: Dimitrova
authors.forename: Lilian
authors.initials: L
authors.lastname: Yamasaki
authors.forename: Pavel
authors.initials: P
authors.lastname: Skums
authors.forename: Daryl Ty
authors.initials: DT
authors.lastname: Lau
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vaughan
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Forbi
authors.forename: Chong-Gee
authors.initials: CG
authors.lastname: Teo
authors.forename: Yury
authors.initials: Y
authors.lastname: Khudyakov
mesh_terms: D003198:Computer Simulation; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000635:transmission; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D016485:Needle Sharing; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D012367:RNA, Viral
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