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Identification of methylation states of DNA regions for Illumina methylation BeadChip
BMC Genomics ( IF 3.5 ) Pub Date : 2020-03-05 , DOI: 10.1186/s12864-019-6019-0
Ximei Luo , Fang Wang , Guohua Wang , Yuming Zhao

Methylation of cytosine bases in DNA is a critical epigenetic mark in many eukaryotes and has also been implicated in the development and progression of normal and diseased cells. Therefore, profiling DNA methylation across the genome is vital to understanding the effects of epigenetic. In recent years the Illumina HumanMethylation450 (HM450K) and MethylationEPIC (EPIC) BeadChip have been widely used to profile DNA methylation in human samples. The methods to predict the methylation states of DNA regions based on microarray methylation datasets are critical to enable genome-wide analyses. We report a computational approach based on the two layers two-state hidden Markov model (HMM) to identify methylation states of single CpG site and DNA regions in HM450K and EPIC BeadChip. Using this mothed, all CpGs detected by HM450K and EPIC in H1-hESC and GM12878 cell lines are identified as un-methylated, middle-methylated and full-methylated states. A large number of DNA regions are segmented into three methylation states as well. Comparing the identified regions with the result from the whole genome bisulfite sequencing (WGBS) datasets segmented by MethySeekR, our method is verified. Genome-wide maps of chromatin states show that methylation state is inversely correlated with active histone marks. Genes regulated by un-methylated regions are expressed and regulated by full-methylated regions are repressed. Our method is illustrated to be useful and robust. Our method is valuable for DNA methylation genome-wide analyses. It is focusing on identification of DNA methylation states on microarray methylation datasets. For the features of array datasets, using two layers two-state HMM to identify to methylation states on CpG sites and regions creatively, our method which takes into account the distribution of genome-wide methylation levels is more reasonable than segmentation with a fixed threshold.

中文翻译:

识别Illumina甲基化BeadChip DNA区域的甲基化状态

DNA中胞嘧啶碱基的甲基化是许多真核生物中至关重要的表观遗传标记,还与正常细胞和患病细胞的发育和进程有关。因此,对整个基因组进行DNA甲基化分析对于了解表观遗传学的影响至关重要。近年来,Illumina HumanMethylation450(HM450K)和MethylationEPIC(EPIC)BeadChip已被广泛用于分析人类样品中的DNA甲基化。基于微阵列甲基化数据集预测DNA区域甲基化状态的方法对于实现全基因组分析至关重要。我们报告了一种基于两层两态隐藏马尔可夫模型(HMM)的计算方法,以确定HM450K和EPIC BeadChip中单个CpG位点和DNA区域的甲基化状态。用这种方法 HM450K和EPIC在H1-hESC和GM12878细胞系中检测到的所有CpG均被鉴定为未甲基化,中甲基化和全甲基化状态。大量的DNA区域也被分成三个甲基化状态。将识别的区域与由MethySeekR分割的全基因组亚硫酸氢盐测序(WGBS)数据集的结果进行比较,验证了我们的方法。染色质状态的全基因组图谱显示甲基化状态与活性组蛋白标记呈负相关。表达受未甲基化区域调节的基因,并抑制受全甲基化区域调节的基因。我们的方法被证明是有用和健壮的。我们的方法对于全基因组DNA甲基化分析非常有价值。它着重于在微阵列甲基化数据集上鉴定DNA甲基化状态。
更新日期:2020-03-06
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