DeepSignal: detecting DNA methylation state from Nanopore sequencing reads using deep-learning
DeepSignal: detecting DNA methylation state from Nanopore sequencing reads using deep-learning
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DOI：
10.1093/bioinformatics/btz276
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发表时间：
2019-11-15
期刊：
影响因子：
5.8
通讯作者：
Wang, Jianxin
中科院分区：
文献类型：
--
作者：
Ni, Peng;Huang, Neng;Wang, Jianxin
动机：Oxford Nanopore测序能够直接检测DNA中碱基的甲基化状态，而无需额外的实验室技术。需要新的计算方法来提高使用Nanopore reads.Results的DNA甲基化状态预测的准确性和鲁棒性：在这项研究中，我们开发了DeepSignal，这是一种深度学习方法，可以从Nanopore测序reads中检测DNA甲基化状态。对智人（Homo sapiens）的纳米孔读数的测试（H. sapiens）、大肠杆菌（E. coli）和pUC19的结果表明，与先前基于隐马尔可夫模型（HMM）的方法相比，DeepSignal在检测6mA和5mC甲基化状态时可以在读取水平和基因组水平上实现更高的性能。DeepSignal在不同的DNA甲基化碱基、不同的DNA甲基化基序以及单一和混合的DNA CpG之间实现了类似的性能。此外，DeepSignal所需的覆盖率比HMM和基于统计的方法所需的覆盖率低得多。DeepSignal可以实现90%以上的准确度，检测5mC和6mA，仅使用2x读数覆盖率。此外，对于DNA CpG甲基化状态预测，DeepSignal仅使用20倍的读数覆盖率就实现了与亚硫酸氢盐测序的90%相关性，这比基于HMM的方法要好得多。特别是，DeepSignal可以预测5%以上的DNA CpG的甲基化状态，这是以前无法通过亚硫酸氢盐测序预测的。DeepSignal可以是一种用于检测DNA碱基甲基化状态的鲁棒且准确的方法。
Motivation: The Oxford Nanopore sequencing enables to directly detect methylation states of bases in DNA from reads without extra laboratory techniques. Novel computational methods are required to improve the accuracy and robustness of DNA methylation state prediction using Nanopore reads.Results: In this study, we develop DeepSignal, a deep learning method to detect DNA methylation states from Nanopore sequencing reads. Testing on Nanopore reads of Homo sapiens (H. sapiens), Escherichia coli (E. coli) and pUC19 shows that DeepSignal can achieve higher performance at both read level and genome level on detecting 6mA and 5mC methylation states comparing to previous hidden Markov model (HMM) based methods. DeepSignal achieves similar performance cross different DNA methylation bases, different DNA methylation motifs and both singleton and mixed DNA CpG. Moreover, DeepSignal requires much lower coverage than those required by HMM and statistics based methods. DeepSignal can achieve 90% above accuracy for detecting 5mC and 6mA using only 2x coverage of reads. Furthermore, for DNA CpG methylation state prediction, DeepSignal achieves 90% correlation with bisulfite sequencing using just 20x coverage of reads, which is much better than HMM based methods. Especially, DeepSignal can predict methylation states of 5% more DNA CpGs that previously cannot be predicted by bisulfite sequencing. DeepSignal can be a robust and accurate method for detecting methylation states of DNA bases.