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Correction for Quer at al., High-Resolution Hepatitis C Virus Subtyping Using NS5B Deep Sequencing and Phylogeny, an Alternative to Current Methods

机译:使用NS5B深度测序和系统发生方法(目前方法的替代方法)对高分辨率丙型肝炎病毒亚型进行校正

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摘要

HepatitisCvirus (HCV)is classified into seven major genotypesand67 subtypes. Recent studies haveshownthat inHCVgenotype 1-infected patients, response rates to regimens containingdirect-acting antivirals(DAAs)are subtype dependent. Currently available genotypingmethods have limited subtyping accuracy.Wehave evaluated theperformanceof adeep-sequencing-basedHCVsubtyping assay, developed for the 454/GS-Junior platform, incomparisonwith thoseof twocommercial assays (VersantHCVgenotype 2.0andAbbott Real-timeHCVGenotype II)andusingdirectNS5Bsequencing as a gold standard (direct sequencing), in 114 clinical specimenspreviously tested by first-generation hybridization assay (82 genotype 1 and32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 callingbypopulation Sanger sequencing (69%1b,31%1a) in81 specimensandidentified amixed-subtype infection (1b/3a/1a) inone sample. Similarly,amongthe 32previously indeterminate specimens, identical genotypeandsubtype results were obtained by directanddeep sequencing inall but four samples with dual infection. In contrast, both VersantHCVGenotype 2.0andAbbott Real-timeHCVGenotype II failed subtype 1 calling in13 (16%)samples eachandwere unable to identify theHCVgenotype and/or subtype inmore thanhalfof the nongenotype 1 samples.Weconcluded that deep sequencing ismore efficient forHCVsubtyping than currently available methods andallows qualitative identificationofmixed infectionsandmay bemorehelpfulwith respect toinforming treatment strategies withnewDAA-containing regimens across allHCVsubtypes
机译:丙型肝炎病毒(HCV)被分为7个主要基因型和67个亚型。最近的研究表明,在感染了HCV基因型1的患者中,对包含直接作用抗病毒药物(DAA)的治疗方案的反应率取决于亚型。目前可用的基因分型方法的分型准确性有限。我们已经评估了针对454 / GS-Junior平台开发的基于深度测序的HCV分型分析的性能,与两种商业分析(VersantHCV基因型2.0和Abbott实时HCV基因型II)以及直接使用NS5B测序的商业化方法进行了比较在114份先前通过第一代杂交测定法检测的临床标本中(82个基因型1和32,结果无法解释)。深度测序的系统发生分析读取了81个样本中符合种群Sanger测序(69%1b,31%1a)的匹配的亚型1并鉴定了一个样本中的混合亚型感染(1b / 3a / 1a)。同样,在32个先前不确定的标本中,通过直接和深层测序对除了四个双重感染的所有样品进行了直接和深度测序,获得了相同的基因型和亚型结果。相比之下,VersantHCV基因型2.0和Abbott Real-time HCV基因型II失败的亚型1分别调用了13个样本(16%),无法识别出非基因型1样本的一半以上的HCV基因型和/或亚型。鉴定混合感染,对于在所有HCV亚型中采用新的含DAA方案的治疗策略,为指导治疗策略提供更多帮助

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