Metagenomics Strain Resolution on Assembly Graphs

Metagenomics Strain Resolution on Assembly Graphs
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组装图上的宏基因组应变解析

DOI:
10.1101/2020.09.06.284828
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发表时间:
2020
期刊:
bioRxiv
影响因子:
--
通讯作者:
A. E. Darling
A. E. Darling
中科院分区:
--
文献类型:
--
作者:
C. Quince;S. Nurk;S. Raguideau;Robert S James;Orkun S. Soyer;J. Summers;A. Limasset;A. M. Eren;R. Chikhi;A. E. Darling

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我们介绍了一种新的生物信息学管道,装配图上的菌株分解(STRONG),当来自同一群落的多个元基因组样本可用时,它从新识别菌株。Strong执行共组装,然后绑定到元基因组组装基因组(MAG)中,但唯一的是,它在简化变体之前存储共组装图。这使得能够提取每个MAG中的单个单拷贝核心基因(SCG)的子图。然后,它可以回溯从样本中读取的数据,以计算这些图中单位的每个样本覆盖率。这些曲线图及其单位覆盖率随后被用于贝叶斯算法BayesPath,该算法确定存在的菌株数量、它们在SCG上的序列或单倍型以及它们在每个样本中的丰度。我们的方法既避免了READ图谱的模棱两可,又允许利用比单独处理变体时更多的关于变体在READ中共同出现的信息,同时利用当它们在同一品系中连锁时跨样本发生的变体的相关性。我们比较了合成群落的当前技术状态,并证明了我们可以更准确地恢复更多的菌株,并且使用用于应变解析的变分贝叶斯算法得出的不确定性的现实估计。在一个真实的厌氧消化器时间序列上,我们获得了300多个菌体的菌株分解的SCG,对于丰富的群落成员来说,这与从长纳米孔读数中观察到的相匹配。
We introduce a novel bioinformatics pipeline, STrain Resolution ON assembly Graphs (STRONG), which identifies strains de novo, when multiple metagenome samples from the same community are available. STRONG performs coassembly, followed by binning into metagenome assembled genomes (MAGs), but uniquely it stores the coassembly graph prior to simplification of variants. This enables the subgraphs for individual single-copy core genes (SCGs) in each MAG to be extracted. It can then thread back reads from the samples to compute per sample coverages for the unitigs in these graphs. These graphs and their unitig coverages are then used in a Bayesian algorithm, BayesPaths, that determines the number of strains present, their sequences or haplotypes on the SCGs and their abundances in each of the samples. Our approach both avoids the ambiguities of read mapping and allows more of the information on co-occurrence of variants in reads to be utilised than if variants were treated independently, whilst at the same time exploiting the correlation of variants across samples that occurs when they are linked in the same strain. We compare STRONG to the current state of the art on synthetic communities and demonstrate that we can recover more strains, more accurately, and with a realistic estimate of uncertainty deriving from the variational Bayesian algorithm employed for the strain resolution. On a real anaerobic digestor time series we obtained strain-resolved SCGs for over 300 MAGs that for abundant community members match those observed from long Nanopore reads.
DOI: --
发表时间: --
影响因子: 5.3
作者:
A. M. Eren;A. Murat Eren;Ozcan C Esen;C. Quince;Joseph H Vineis;H. Morrison;M. Sogin;Tom O. Delmont-Tom-O.-D
通讯作者: A. M. Eren;A. Murat Eren;Ozcan C Esen;C. Quince;Joseph H Vineis;H. Morrison;M. Sogin;Tom O. Delmont-Tom-O.-D