MinVar: A rapid and versatile tool for HIV-1 drug resistance genotyping by deep sequencing
MinVar: A rapid and versatile tool for HIV-1 drug resistance genotyping by deep sequencing
复制标题
DOI：
10.1016/j.jviromet.2016.11.008
复制
发表时间：
2017-02-01
影响因子：
3.1
通讯作者：
Zagordi, Osvaldo
中科院分区：
文献类型：
--
作者：
Huber, Michael;Metzner, Karin J.;Zagordi, Osvaldo
强烈建议对HIV-1感染者的耐药突变（DRMs）进行基因型监测，以指导初始抗逆转录病毒治疗（ART）的选择和药物方案的改变。传统上，通过ART对编码HIV-1酶靶标的逆转录病毒RNA进行群体测序，然后对桑格测序痕迹进行手动分析和解释，来检测赋予耐药性的突变。这个过程是劳动密集型的，依赖于操作者的主观解释，并且提供有限的灵敏度，因为只有高于20%频率的突变才能被可靠地检测到。在这里，我们介绍了MinVar，这是一种用于分析深度测序数据的管道，它可以可靠地自动检测低至5%的DRM。我们使用来自具有已知DRM的分子病毒克隆的定义混合物的扩增子测序数据和病毒血症HIV-1感染个体的血浆样本评估了MinVar，并将其与VirVarSeq进行了比较，VirVarSeq是另一种专门用于Illumina深度测序数据的病毒变体检测工具。MinVar被设计为与各种测序平台兼容，并允许从深度测序数据中检测DRM和插入/缺失，而无需进行额外的生物信息学分析，这是在常规诊断环境中使用深度测序广泛实施HIV-1基因分型的先决条件。(C)2016作者由Elsevier B. V.发布，这是CC BY许可下的开放获取文章。
Genotypic monitoring of drug-resistance mutations (DRMs) in HIV-1 infected individuals is strongly recommended to guide selection of the initial antiretroviral therapy (ART) and changes of drug regimens. Traditionally, mutations conferring drug resistance are detected by population sequencing of the reverse transcribed viral RNA encoding the HIV-1 enzymes target by ART, followed by manual analysis and interpretation of Sanger sequencing traces. This process is labor intensive, relies on subjective interpretation from the operator, and offers limited sensitivity as only mutations above 20% frequency can be reliably detected. Here we present MinVar, a pipeline for the analysis of deep sequencing data, which allows reliable and automated detection of DRMs down to 5%. We evaluated MinVar with data from amplicon sequencing of defined mixtures of molecular virus clones with known DRM and plasma samples of viremic HIV-1 infected individuals and we compared it to VirVarSeq, another virus variant detection tool exclusively working on Illumina deep sequencing data. MinVar was designed to be compatible with a diverse range of sequencing platforms and allows the detection of DRMs and insertions/deletions from deep sequencing data without the need to perform additional bioinformatics analysis, a prerequisite to a widespread implementation of HIV-1 genotyping using deep sequencing in routine diagnostic settings. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.