IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth

IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth
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DOI:
10.1093/bioinformatics/bts174
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发表时间:
2012-06-01
期刊:
影响因子:
5.8
通讯作者:
Chin, Francis Y. L.
Chin, Francis Y. L.
中科院分区:
生物学3区
文献类型:
--
作者:
Peng, Yu;Leung, Henry C. M.;Chin, Francis Y. L.

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动机:下一代测序允许我们使用单细胞测序或宏基因组测序技术对来自微生物环境的读数进行测序。然而,这两种技术都存在基因组的不同区域或来自不同物种的基因组的测序深度高度不均匀的问题。大多数现有的基因组组装器通常假设测序深度是均匀的。这些装配器无法构建正确的长contigs.Results:我们介绍了IDBA-UD算法,该算法是基于de Bruijn图方法,用于装配来自单细胞测序或宏基因组测序技术的具有不均匀测序深度的读段。已经采用了几种重要的技术来解决这些问题。而不是使用一个简单的阈值,我们使用多个depthrelative阈值,以消除错误的k-mer在低深度和高深度区域。利用末端配对信息的局部组装技术解决了低深度短重复区的分支问题。为了加速该过程,进行错误校正步骤以校正可以与高置信度重叠群比对的高深度区域的读数。比较IDBA-UD和现有的组装器(Velvet,Velvet-SC,SOAPDenovo和Meta-IDBA)在不同数据集上的性能,表明IDBA-UD可以以更高的精度重建更长的重叠群。
Motivation: Next-generation sequencing allows us to sequence reads from a microbial environment using single-cell sequencing or metagenomic sequencing technologies. However, both technologies suffer from the problem that sequencing depth of different regions of a genome or genomes from different species are highly uneven. Most existing genome assemblers usually have an assumption that sequencing depths are even. These assemblers fail to construct correct long contigs.Results: We introduce the IDBA-UD algorithm that is based on the de Bruijn graph approach for assembling reads from single-cell sequencing or metagenomic sequencing technologies with uneven sequencing depths. Several non-trivial techniques have been employed to tackle the problems. Instead of using a simple threshold, we use multiple depthrelative thresholds to remove erroneous k-mers in both low-depth and high-depth regions. The technique of local assembly with paired-end information is used to solve the branch problem of low-depth short repeat regions. To speed up the process, an error correction step is conducted to correct reads of high-depth regions that can be aligned to highconfident contigs. Comparison of the performances of IDBA-UD and existing assemblers (Velvet, Velvet-SC, SOAPdenovo and Meta-IDBA) for different datasets, shows that IDBA-UD can reconstruct longer contigs with higher accuracy.