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Xanquan Zhan\*, Tian Zhou, Tingting Cheng and Miaolong Lu Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, China

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10.1002/pmic.201100520

10.1016/j.cell.2008.08.026

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134050

2004;**325**:1180-1186

**72**

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**75**

**Chapter 5**

**Abstract**

HCV Genotyping with Concurrent

Profiling of Resistance-Associated

Determination of viral characteristics including genotype (GT), subtype (ST) and resistance-associated variants (RAVs) profile is important in assigning direct-acting antivirals regimes in HCV patients. To help achieve the best clinical management of HCV patients, a routine diagnostic laboratory should aim at reporting accurate viral GT/ST and RAVs using a reliable diagnostic platform of choice. A laboratory study was conducted to evaluate performance characteristics of a new commercial next-generation sequencing (NGS)-based HCV genotyping assay in comparison to another widely used commercial line probe assay for HCV genotyping. Information on RAVs from deeply sequenced NS3, NS5A and NS5B regions in samples classified as HCV 1a and 1b was harnessed from the fully automated software. Perfect (100%) concordance at HCV genotype level was achieved in GT2 (N = 13), GT3 (N = 55) and GT5 (N = 7). NGS refined the ST assignment in GTs 1, 4 and 6, and resolved previously indeterminate GTs reported by line probe assay. NGS was found to have consistent intra- and inter-run reproducibility in terms of genotyping, subtyping and RAVs identification. Detection of infections with multiple HCV GTs or STs is feasible by NGS. Deep sequencing allows sensitive identification of RAVs in the GT 1a and 1b NS3, NS5A and NS5B regions, but the list

**Keywords:** resistance-associated variants, next-generation sequencing,

Due to the genetic diversity of the hepatitis C virus (HCV), its accurate genotyping is still currently challenging despite the use of modern molecular techniques. In addition to the six widely-recognised HCV genotypes, a newly identified genotype (GT) 7 was reported in 2015 [1]. Molecular methods including reverse hybridization, real-time PCR and Sanger sequencing are commonly utilised for HCV genotyping and subtyping in clinical laboratories. HCV genotype and subtype (ST) have been the critical factors in decision-making for administering interferon-based therapies for the past decade [2]. According to the latest AASLD guidelines [3], determination of viral characteristics including GT, ST and resistance-associated variants (RAVs) profile is important in assigning direct-acting antivirals (DAAs) regimes in HCV patients.

Variants by NGS Analysis

*Kok-Siong Poon, Julian Wei-Tze Tang* 

*and Evelyn Siew-Chuan Koay*

of target RAVs is not exhaustive.

hepatitis C, HCV genotyping, NGS

**1. Introduction**

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**Chapter 5**

*Bioinformatics Tools for Detection and Clinical Interpretation of Genomic Variations*

[109] Nam H, Chung BC, Kim Y, Lee K, Lee D. Combining tissue

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DOI: 10.1073/pnas.1523434113

for breast cancer biomarker identification. Bioinformatics. 2009;**25**:3151-3157. DOI: 10.1093/

bioinformatics/btp558

transcriptomics and urine metabolomics

**74**
