VirGenA: a reference-based assembler for variable viral genomes

VirGenA: a reference-based assembler for variable viral genomes
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DOI:
10.1093/bib/bbx079
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发表时间:
2019-01-01
影响因子:
9.5
通讯作者:
Neverov, Alexey D.
Neverov, Alexey D.
中科院分区:
生物学2区
文献类型:
--
作者:
Fedonin, Gennady G.;Fantin, Yury S.;Neverov, Alexey D.

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为了选择有效治疗一些重要的病毒感染,如HIV、HBV和HCV,需要对宿主内病毒病原体的遗传多样性进行表征。尽管有检测的技术能力,但关于低频变异的临床意义存在相互矛盾的数据,部分原因是它们难以与实验伪像区分开来。交叉污染问题与所有高度敏感的技术相关,包括深度测序:即使是微量污染也会导致鉴定出的snv的假阳性显著增加。在某些情况下,确定某些病毒的多种基因型感染也具有临床意义,这些病毒的发病率可能相当高,特别是在危险人群中。我们开发了一种新的病毒参考引导组装器,VirGenA,它可以分离不同物种遗传群(基因型,亚型,枝等)的菌株混合物,并在混合物中为每个组组装单独的共识序列。它为极低频率的混合组件生产长组件(
Characterization of the within-host genetic diversity of viral pathogens is required for selection of effective treatment of some important viral infections, e.g. HIV, HBV and HCV. Despite the technical ability of detection, there are conflicting data regarding the clinical significance of low-frequency variants, partially because of the difficulty of their distinguishing from experimental artifacts. The issue of cross-contamination is relevant for all highly sensitive techniques, including deep sequencing: even trace contamination leads to a significant increase of false positives in identified SNVs. Determination of infections by multiple genotypes of some viruses, the incidence of which can be considerable, especially in risk groups, is also clinically significant in some cases. We developed a new viral reference-guided assembler, VirGenA, that can separate mixtures of strains of different in traspecies genetic groups (genotypes, subtypes, clades, etc.) and assemble a separate consensus sequence for each group in a mixture. It produced long assemblies for mixture components of extremely low frequencies (