Viral quasispecies assembly via maximal clique enumeration.
Viral quasispecies assembly via maximal clique enumeration.
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DOI：
10.1371/journal.pcbi.1003515
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发表时间：
2014-03
影响因子：
4.3
通讯作者：
Beerenwinkel N
中科院分区：
文献类型：
--
作者：
Töpfer A;Marschall T;Bull RA;Luciani F;Schönhuth A;Beerenwinkel N
病毒种群在个体宿主内可以表现出高度的遗传多样性。病毒单倍型的宿主内集合，称为病毒准种，是毒力、发病机制和治疗结果的重要决定因素。我们提出了 HaploClique，一种计算方法，可根据混合病毒样本批量测序获得的下一代测序数据重建病毒准种的结构。我们开发了一个用于解释突变、插入和删除的双端读取的统计模型。使用迭代最大团枚举方法，读取对被组装成长度不断增加的单倍型，最终实现全局单倍型组装。我们的准种组装方法的性能是根据不同种群特征和测序技术参数的模拟数据进行评估的。由于其双端处理，HaploClique 与最先进的单倍型推断方法相比具有优势。它可以从低覆盖率样本中重建无错误的全长单倍型，并检测低频的大插入和缺失。我们应用 HaploClique 对来自受感染患者的临床丙型肝炎病毒群体的测序数据，发现了长度为 357±167 bp 的新缺失，并通过两个独立的长读长测序实验进行了验证。 HaploClique 可在 https://github.com/armintoepfer/haploclique 获取。本文的摘要出现在 4 月 2 日至 5 日举行的 RECOMB 2014 会议的会议记录中。感染人类免疫缺陷病毒 (HIV-1) 或丙型肝炎病毒 (HCV) 等病毒的人类体内携带着数十亿的病毒颗粒。其中，有数量未知的基因不同菌株，其中一些可能含有耐药性和免疫逃逸突变。了解这些变异的 DNA 序列和丰度具有重要的临床意义，因为它们会影响治疗结果。在这里，我们提出了 HaploClique，一种用于重建这些序列并从配对末端下一代测序数据中预测大量插入和删除的计算方法。通过模拟，我们证明 HaploClique 可以从低覆盖率样本中重建全长 HIV-1 变体。使用真实世界的临床数据，我们预测 HCV 患者样本中存在 357±167 bp 的新缺失，该缺失已通过两个独立的长读长测序实验进行验证。
Virus populations can display high genetic diversity within individual hosts. The intra-host collection of viral haplotypes, called viral quasispecies, is an important determinant of virulence, pathogenesis, and treatment outcome. We present HaploClique, a computational approach to reconstruct the structure of a viral quasispecies from next-generation sequencing data as obtained from bulk sequencing of mixed virus samples. We develop a statistical model for paired-end reads accounting for mutations, insertions, and deletions. Using an iterative maximal clique enumeration approach, read pairs are assembled into haplotypes of increasing length, eventually enabling global haplotype assembly. The performance of our quasispecies assembly method is assessed on simulated data for varying population characteristics and sequencing technology parameters. Owing to its paired-end handling, HaploClique compares favorably to state-of-the-art haplotype inference methods. It can reconstruct error-free full-length haplotypes from low coverage samples and detect large insertions and deletions at low frequencies. We applied HaploClique to sequencing data derived from a clinical hepatitis C virus population of an infected patient and discovered a novel deletion of length 357±167 bp that was validated by two independent long-read sequencing experiments. HaploClique is available at https://github.com/armintoepfer/haploclique. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5. Humans infected with a virus, such as the human immunodeficiency virus (HIV-1) or hepatitis C virus (HCV), host a population of billions of virus particles. Among these, there is an unknown number of genetically different strains, some of which can harbor drug resistance and immune escape mutations. It is of clinical importance to know the DNA sequences and abundances of these variants, as they can affect treatment outcome. Here, we present HaploClique, a computational approach to reconstruct these sequences and to predict large insertions and deletions from paired-end next-generation sequencing data. Using simulations, we demonstrate that HaploClique can reconstruct full-length HIV-1 variants from low-coverage samples. Using real-world clinical data, we predict a novel deletion of 357±167 bp in a HCV patient sample that has been validated by two independent long-read sequencing experiments.
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影响因子：
4.4
作者：
O'Neil ST;Emrich SJ
通讯作者：
Emrich SJ
影响因子：
1.7
作者：
Aguiar, Derek;Istrail, Sorin
通讯作者：
Istrail, Sorin
DOI：
10.1093/bioinformatics/btp692
发表时间：
2010-02-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Li B;Ruotti V;Stewart RM;Thomson JA;Dewey CN
通讯作者：
Dewey CN
影响因子：
30.8
作者：
Hinkley, Trevor;Martins, Joao;Bonhoeffer, Sebastian
通讯作者：
Bonhoeffer, Sebastian
影响因子：
4.3
作者：
Macalalad AR;Zody MC;Charlebois P;Lennon NJ;Newman RM;Malboeuf CM;Ryan EM;Boutwell CL;Power KA;Brackney DE;Pesko KN;Levin JZ;Ebel GD;Allen TM;Birren BW;Henn MR
通讯作者：
Henn MR