Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing

STOP-HCV Consortium

doi:10.1016/j.cmi.2021.06.042

Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing

STOP-HCV Consortium

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Objectives: We sought to evaluate clinically a hepatitis C virus (HCV) whole-genome, next-generation sequencing (NGS) pipeline that is agnostic to viral genotype.

Methods: Performance of the NGS pipeline was assessed through comparison of results with Sanger sequencing (SS) of partial HCV genomes.

Results: There was 98.7% (376/381) concordance for viral subtype between SS and NGS. The positive and negative per cent agreements for determination of resistance-associated substitutions were 97.8% (95% CI 92.5–99.4%) and 99.9% (95% CI 99.5–100.0%), respectively. The NGS pipeline was also able to detect novel subtypes, mixtures, recombinants, transiently occurring resistance mutations and distinguish re-infection with the same subtype from relapse.

Discussion: Particular scenarios where NGS may be used include settings without universal access to pan-genotypic antiviral regimens, those infected with a ‘rare’ subtype or who have been failed by first-line therapy, and in cases of suspected re-infection.

Original language	English
Pages (from-to)	405-409
Number of pages	5
Journal	Clinical Microbiology and Infection
Volume	28
Issue number	3
Early online date	7 Jul 2021
DOIs	https://doi.org/10.1016/j.cmi.2021.06.042
Publication status	Published - 10 Mar 2022

Bibliographical note

Funding Information: This work was funded by Public Health England and a grant from the Medical Research Council MR/K01532X/1 to the STOP-HCV consortium (Stratified Medicine to Optimize patient outcome with HCV infection). The authors do not have an association that might pose a conflict of interest.

Open Access: No Open Access licence.

Publisher Copyright: Crown Copyright © 2021 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

Citation: Bradshaw, Daniel, et al. "Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing." Clinical Microbiology and Infection (2021).

DOI: https://doi.org/10.1016/j.cmi.2021.06.042

Keywords

Clinical evaluation
Genotyping
Hepatitis C virus (HCV)
Resistance testing
Whole-genome sequencing

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmi.2021.06.042

Cite this

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title = "Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing",

abstract = "Objectives: We sought to evaluate clinically a hepatitis C virus (HCV) whole-genome, next-generation sequencing (NGS) pipeline that is agnostic to viral genotype. Methods: Performance of the NGS pipeline was assessed through comparison of results with Sanger sequencing (SS) of partial HCV genomes. Results: There was 98.7% (376/381) concordance for viral subtype between SS and NGS. The positive and negative per cent agreements for determination of resistance-associated substitutions were 97.8% (95% CI 92.5–99.4%) and 99.9% (95% CI 99.5–100.0%), respectively. The NGS pipeline was also able to detect novel subtypes, mixtures, recombinants, transiently occurring resistance mutations and distinguish re-infection with the same subtype from relapse. Discussion: Particular scenarios where NGS may be used include settings without universal access to pan-genotypic antiviral regimens, those infected with a {\textquoteleft}rare{\textquoteright} subtype or who have been failed by first-line therapy, and in cases of suspected re-infection.",

keywords = "Clinical evaluation, Genotyping, Hepatitis C virus (HCV), Resistance testing, Whole-genome sequencing",

author = "{STOP-HCV Consortium} and Daniel Bradshaw and Bibby, {David F.} and Manso, {Carmen F.} and Renata Piorkowska and Hodan Mohamed and Juan Ledesma and Laura Bubba and Chan, {Yuen T.} and Ngui, {Siew Lin} and Simon Carne and Mbisa, {Jean L.}",

note = "Funding Information: This work was funded by Public Health England and a grant from the Medical Research Council MR/K01532X/1 to the STOP-HCV consortium (Stratified Medicine to Optimize patient outcome with HCV infection). The authors do not have an association that might pose a conflict of interest. Open Access: No Open Access licence. Publisher Copyright: Crown Copyright {\textcopyright} 2021 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. All rights reserved. Citation: Bradshaw, Daniel, et al. {"}Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing.{"} Clinical Microbiology and Infection (2021). DOI: https://doi.org/10.1016/j.cmi.2021.06.042",

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doi = "10.1016/j.cmi.2021.06.042",

language = "English",

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journal = "Clinical Microbiology and Infection",

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T1 - Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing

AU - STOP-HCV Consortium

AU - Bradshaw, Daniel

AU - Bibby, David F.

AU - Manso, Carmen F.

AU - Piorkowska, Renata

AU - Mohamed, Hodan

AU - Ledesma, Juan

AU - Bubba, Laura

AU - Chan, Yuen T.

AU - Ngui, Siew Lin

AU - Carne, Simon

AU - Mbisa, Jean L.

N1 - Funding Information: This work was funded by Public Health England and a grant from the Medical Research Council MR/K01532X/1 to the STOP-HCV consortium (Stratified Medicine to Optimize patient outcome with HCV infection). The authors do not have an association that might pose a conflict of interest. Open Access: No Open Access licence. Publisher Copyright: Crown Copyright © 2021 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. All rights reserved. Citation: Bradshaw, Daniel, et al. "Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing." Clinical Microbiology and Infection (2021). DOI: https://doi.org/10.1016/j.cmi.2021.06.042

PY - 2022/3/10

Y1 - 2022/3/10

N2 - Objectives: We sought to evaluate clinically a hepatitis C virus (HCV) whole-genome, next-generation sequencing (NGS) pipeline that is agnostic to viral genotype. Methods: Performance of the NGS pipeline was assessed through comparison of results with Sanger sequencing (SS) of partial HCV genomes. Results: There was 98.7% (376/381) concordance for viral subtype between SS and NGS. The positive and negative per cent agreements for determination of resistance-associated substitutions were 97.8% (95% CI 92.5–99.4%) and 99.9% (95% CI 99.5–100.0%), respectively. The NGS pipeline was also able to detect novel subtypes, mixtures, recombinants, transiently occurring resistance mutations and distinguish re-infection with the same subtype from relapse. Discussion: Particular scenarios where NGS may be used include settings without universal access to pan-genotypic antiviral regimens, those infected with a ‘rare’ subtype or who have been failed by first-line therapy, and in cases of suspected re-infection.

AB - Objectives: We sought to evaluate clinically a hepatitis C virus (HCV) whole-genome, next-generation sequencing (NGS) pipeline that is agnostic to viral genotype. Methods: Performance of the NGS pipeline was assessed through comparison of results with Sanger sequencing (SS) of partial HCV genomes. Results: There was 98.7% (376/381) concordance for viral subtype between SS and NGS. The positive and negative per cent agreements for determination of resistance-associated substitutions were 97.8% (95% CI 92.5–99.4%) and 99.9% (95% CI 99.5–100.0%), respectively. The NGS pipeline was also able to detect novel subtypes, mixtures, recombinants, transiently occurring resistance mutations and distinguish re-infection with the same subtype from relapse. Discussion: Particular scenarios where NGS may be used include settings without universal access to pan-genotypic antiviral regimens, those infected with a ‘rare’ subtype or who have been failed by first-line therapy, and in cases of suspected re-infection.

KW - Clinical evaluation

KW - Genotyping

KW - Hepatitis C virus (HCV)

KW - Resistance testing

KW - Whole-genome sequencing

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U2 - 10.1016/j.cmi.2021.06.042

DO - 10.1016/j.cmi.2021.06.042

M3 - Article

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SN - 1198-743X

VL - 28

SP - 405

EP - 409

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

IS - 3

ER -

Clinical evaluation of a Hepatitis C Virus whole-genome sequencing pipeline for genotyping and resistance testing

Abstract

Bibliographical note

Keywords

UN SDGs

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