De novo assembly of highly diverse viral populations.
De novo assembly of highly diverse viral populations.
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DOI：
10.1186/1471-2164-13-475
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发表时间：
2012-09-13
期刊：
影响因子：
4.4
通讯作者：
Henn MR
中科院分区：
文献类型：
--
作者：
Yang X;Charlebois P;Gnerre S;Coole MG;Lennon NJ;Levin JZ;Qu J;Ryan EM;Zody MC;Henn MR
受感染宿主内病毒群体的广泛遗传多样性以及变异体与现有参考基因组的差异阻碍了对深度病毒测序数据的分析。从头群体共识组装作为群体的单一线性表示和作为可以准确映射宿主内变异的主干都很有价值。一致性组装和稳健映射的变体的可用性对于病毒疾病进展、传播动力学和病毒进化的遗传学研究至关重要。由于存在广泛的遗传变异性、污染物和可变序列覆盖，现有的从头组装技术无法将来自遗传异质群体（如病毒）的超深度序列数据稳健地组装成全长基因组。我们提出维库纳，从头组装算法，适合于从遗传异质性群体产生共识组件。我们证明了它对登革热，人类免疫缺陷和西尼罗河病毒种群的有效性，代表了一系列宿主内的多样性。与为单倍体或二倍体系统设计的最先进的组装器相比，维库纳恢复全长共识并捕获不同样品中的插入/缺失多态性。最终组装保持高的碱基识别准确度。维库纳程序可在以下网址公开获得：http://www.broadinstitute.org/scientific-community/science/projects/viral-genomics/ viral-genomics-analysis-software。我们开发了维库纳，这是一种公开可用的软件工具，可以实现来自不同病毒群体的超深层序列的共识组装。虽然维库纳是为分析病毒群体而开发的，但其应用于其他异质序列数据集，如宏基因组或肿瘤细胞群体样本，可能在这些研究领域中证明是有益的。
Extensive genetic diversity in viral populations within infected hosts and the divergence of variants from existing reference genomes impede the analysis of deep viral sequencing data. A de novo population consensus assembly is valuable both as a single linear representation of the population and as a backbone on which intra-host variants can be accurately mapped. The availability of consensus assemblies and robustly mapped variants are crucial to the genetic study of viral disease progression, transmission dynamics, and viral evolution. Existing de novo assembly techniques fail to robustly assemble ultra-deep sequence data from genetically heterogeneous populations such as viruses into full-length genomes due to the presence of extensive genetic variability, contaminants, and variable sequence coverage. We present VICUNA, a de novo assembly algorithm suitable for generating consensus assemblies from genetically heterogeneous populations. We demonstrate its effectiveness on Dengue, Human Immunodeficiency and West Nile viral populations, representing a range of intra-host diversity. Compared to state-of-the-art assemblers designed for haploid or diploid systems, VICUNA recovers full-length consensus and captures insertion/deletion polymorphisms in diverse samples. Final assemblies maintain a high base calling accuracy. VICUNA program is publicly available at: http://www.broadinstitute.org/scientific-community/science/projects/viral-genomics/ viral-genomics-analysis-software. We developed VICUNA, a publicly available software tool, that enables consensus assembly of ultra-deep sequence derived from diverse viral populations. While VICUNA was developed for the analysis of viral populations, its application to other heterogeneous sequence data sets such as metagenomic or tumor cell population samples may prove beneficial in these fields of research.
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