DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation.
DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation.
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牛津纳米孔测序的DNA甲基化呼叫工具：一项调查和人类表观基因组范围的评估。
DOI：
10.1186/s13059-021-02510-z
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发表时间：
2021-10-18
期刊：
影响因子：
12.3
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Liu Y;Rosikiewicz W;Pan Z;Jillette N;Wang P;Taghbalout A;Foox J;Mason C;Carroll M;Cheng A;Li S
纳米孔长读测序技术大大扩展了长距离单分子DNA修饰检测的能力。已经开发了越来越多的分析工具来检测来自纳米孔测序读数的DNA甲基化。在这里，我们评估了不同甲基化调用工具的性能，以提供系统的评估，指导研究人员进行人类表观基因组研究。我们比较了七种分析工具，用于从全基因组规模的人类天然DNA产生的纳米孔长读测序数据中检测DNA甲基化。我们评估了CpG甲基化预测在不同基因组背景、CpG位点覆盖率和每种工具消耗的计算资源中的每读段和每位点性能。这七种工具在评价标准中表现出不同的性能。我们发现，在具有不一致DNA甲基化模式的区域、基因间区域、低CG密度区域和重复区域的甲基化预测在所有工具中都有改进的空间。此外，我们证明了5 hmC水平至少部分地导致了亚硫酸氢盐和纳米孔测序之间的差异。最后，我们提供了一个在线DNA甲基化数据库（https：nanome.jax.org），以显示通过纳米孔测序和亚硫酸氢盐测序数据在不同基因组背景下检测到的DNA甲基化水平。我们的研究是用于检测纳米孔测序中哺乳动物全基因组DNA修饰的计算方法的第一个系统基准。我们为跨平台标准化和评估设计用于使用纳米孔测序进行基因组规模修饰碱基检测的分析工具提供了广泛的基础。在线版本包含补充材料，可通过10.1186/s13059-021-02510-z获得。
Nanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylation from nanopore sequencing reads. Here, we assess the performance of different methylation-calling tools to provide a systematic evaluation to guide researchers performing human epigenome-wide studies. We compare seven analytic tools for detecting DNA methylation from nanopore long-read sequencing data generated from human natural DNA at a whole-genome scale. We evaluate the per-read and per-site performance of CpG methylation prediction across different genomic contexts, CpG site coverage, and computational resources consumed by each tool. The seven tools exhibit different performances across the evaluation criteria. We show that the methylation prediction at regions with discordant DNA methylation patterns, intergenic regions, low CG density regions, and repetitive regions show room for improvement across all tools. Furthermore, we demonstrate that 5hmC levels at least partly contribute to the discrepancy between bisulfite and nanopore sequencing. Lastly, we provide an online DNA methylation database (https://nanome.jax.org) to display the DNA methylation levels detected by nanopore sequencing and bisulfite sequencing data across different genomic contexts. Our study is the first systematic benchmark of computational methods for detection of mammalian whole-genome DNA modifications in nanopore sequencing. We provide a broad foundation for cross-platform standardization and an evaluation of analytical tools designed for genome-scale modified base detection using nanopore sequencing. The online version contains supplementary material available at 10.1186/s13059-021-02510-z.
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影响因子：
4.6
作者：
Chen X;Ashoor H;Musich R;Wang J;Zhang M;Zhang C;Lu M;Li S
通讯作者：
Li S
影响因子：
11
作者：
Clark, Michael B.;Wrzesinski, Tomasz;Tunbridge, Elizabeth M.
通讯作者：
Tunbridge, Elizabeth M.
影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE
影响因子：
64.8
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Goyal, Parveen;Krasteva, Petya V.;Van Genven, Nani;Gubellini, Francesca;Van den Broeck, Imke;Troupiotis-Tsailaki, Anastassia;Jonckheere, Wim;Pehau-Arnaudet, Gerard;Pinkner, Jerome S.;Chapman, Matthew R.;Hultgren, Scott J.;Howorka, Stefan;Fronzes, Remi;Remaut, Han
通讯作者：
Remaut, Han
影响因子：
16.6
作者：
Bowden, Rory;Davies, Robert W.;Donnelly, Peter
通讯作者：
Donnelly, Peter