Empirical validation of viral quasispecies assembly algorithms: state-of-the-art and challenges.

Empirical validation of viral quasispecies assembly algorithms: state-of-the-art and challenges.
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DOI:
10.1038/srep02837
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发表时间:
2013-10-03
期刊:
影响因子:
4.6
通讯作者:
Salemi, Marco
Salemi, Marco
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Prosperi, Mattia C. F.;Yin, Li;Nolan, David J.;Lowe, Amanda D.;Goodenow, Maureen M.;Salemi, Marco

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在基因组长度和分辨率方面,下一代测序(NGS)正在取代用于分析宿主内病毒群体的桑格技术。我们介绍了两个新的经验验证数据集和测试可用的病毒群体组装软件。对两种宿主内病毒群体“准种”样品(1型人类免疫缺陷病毒和丙型肝炎病毒)进行Sanger测序,并使用Roche的454测序平台对受控比例的质粒克隆混合物进行鸟枪测序。在系统发育聚类和与桑格克隆的重组方面比较了不同组装器的性能。系统发育聚类表明,所有的汇编程序捕获的比例最不同的血统,但没有一个能够提供一个高精度/召回权衡。估计的变异频率与原始频率轻度相关。鉴于我们的经验验证确定的现有算法的局限性,需要开发和利用额外的数据集,以建立一个有效的框架,使用NGS的病毒种群重建。
Next generation sequencing (NGS) is superseding Sanger technology for analysing intra-host viral populations, in terms of genome length and resolution. We introduce two new empirical validation data sets and test the available viral population assembly software. Two intra-host viral population ‘quasispecies’ samples (type-1 human immunodeficiency and hepatitis C virus) were Sanger-sequenced, and plasmid clone mixtures at controlled proportions were shotgun-sequenced using Roche's 454 sequencing platform. The performance of different assemblers was compared in terms of phylogenetic clustering and recombination with the Sanger clones. Phylogenetic clustering showed that all assemblers captured a proportion of the most divergent lineages, but none were able to provide a high precision/recall tradeoff. Estimated variant frequencies mildly correlated with the original. Given the limitations of currently available algorithms identified by our empirical validation, the development and exploitation of additional data sets is needed, in order to establish an efficient framework for viral population reconstruction using NGS.
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