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使用非齐次隐马尔可夫模型检测亚硫酸氢盐测序数据中的差异甲基化区域。

Detect differentially methylated regions using non-homogeneous hidden Markov model for bisulfite sequencing data.

作者信息

Chen Yingyu, Kwok Chin Kiu, Jiang Hangjin, Fan Xiaodan

机构信息

Department of Statistics, Zhejiang University City College, Hangzhou, China.

Department of Statistics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

出版信息

Methods. 2021 May;189:34-43. doi: 10.1016/j.ymeth.2020.09.009. Epub 2020 Sep 17.

Abstract

DNA methylation plays an important role in many biological processes and diseases. With the rise of the whole genome bisulfite sequencing technique, aberrant methylation patterns can now be detected by comparing paired normal and disease samples at the single nucleotide level. We develop a novel Bayesian method for detecting differentially methylated regions from paired bisulfite sequencing data, and implement it as a R package called BSDMR. Based on a non-homogeneous hidden Markov model, BSDMR provides a better modeling strategy for the spatial correlation between CpG sites and takes into consideration the relationship between methylation signals from normal and disease samples. Simulations show that BSDMR performs well even under low read depth and has a smaller false discovery rates than existing methods. We also apply BSDMR to the colon cancer data from Gene Expression Omnibus. The detected DMRs are well supported by existing biomedical literatures.

摘要

DNA甲基化在许多生物过程和疾病中发挥着重要作用。随着全基因组亚硫酸氢盐测序技术的兴起,现在可以通过在单核苷酸水平上比较配对的正常样本和疾病样本,来检测异常的甲基化模式。我们开发了一种新颖的贝叶斯方法,用于从配对的亚硫酸氢盐测序数据中检测差异甲基化区域,并将其实现为一个名为BSDMR的R包。基于非齐次隐马尔可夫模型,BSDMR为CpG位点之间的空间相关性提供了更好的建模策略,并考虑了正常样本和疾病样本中甲基化信号之间的关系。模拟结果表明,即使在低读取深度下,BSDMR也表现良好,并且比现有方法具有更低的错误发现率。我们还将BSDMR应用于来自基因表达综合数据库的结肠癌数据。检测到的差异甲基化区域得到了现有生物医学文献的充分支持。

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