A novel principal component based method for identifying differentially methylated regions in Illumina Infinium MethylationEPIC BeadChip data.
A novel principal component based method for identifying differentially methylated regions in Illumina Infinium MethylationEPIC BeadChip data.
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DOI：
10.1080/15592294.2023.2207959
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发表时间：
2023-12
期刊：
影响因子：
3.7
通讯作者：
Logue, Mark W.
中科院分区：
文献类型：
--
作者：
Zheng, Yuanchao;Lunetta, Kathryn L.;Liu, Chunyu;Smith, Alicia K.;Sherva, Richard;Miller, Mark W.;Logue, Mark W.
差异甲基化区域（DMR）是在与表型相关的多个CpG位点上具有甲基化模式的基因组区域。在这项研究中，我们提出了一种基于主成分（PC）的DMR分析方法，用于使用Illumina Infinium MethylationEPIC BeadChip（EPIC）阵列生成的数据。我们通过对协变量区域内CpG的M值进行回归来获得甲基化残差，提取残差的PC，然后组合PC之间的关联信息以获得区域显著性。在确定我们的方法的最终版本之前，在各种条件下估计了基于模拟的全基因组假阳性（GFP）率和真阳性率，我们将其命名为DMRPC。然后，使用DMRPC和另一种DMR方法coMethDMR对发现和复制队列中已知具有多个相关甲基化位点（年龄，性别和吸烟）的几种表型进行表观基因组范围分析。在这两种方法分析的区域中，DMRPC比coMethDMR多识别了50%的全基因组显著的年龄相关DMR。仅通过DMRPC鉴定的基因座的复制率高于仅通过coMethDMR鉴定的基因座的复制率（DMRPC为90%，coMethDMR为76%）。此外，DMRPC确定了中度CpG间相关区域中的可复制关联，这些区域通常不被coMethDMR分析。在性别和吸烟方面，DMRPC的优势不明显。总之，DMRPC是一种新的强大的DMR发现工具，它在CpG之间具有中等相关性的基因组区域中保留了功能。
Differentially methylated regions (DMRs) are genomic regions with methylation patterns across multiple CpG sites that are associated with a phenotype. In this study, we proposed a Principal Component (PC) based DMR analysis method for use with data generated using the Illumina Infinium MethylationEPIC BeadChip (EPIC) array. We obtained methylation residuals by regressing the M-values of CpGs within a region on covariates, extracted PCs of the residuals, and then combined association information across PCs to obtain regional significance. Simulation-based genome-wide false positive (GFP) rates and true positive rates were estimated under a variety of conditions before determining the final version of our method, which we have named DMRPC. Then, DMRPC and another DMR method, coMethDMR, were used to perform epigenome-wide analyses of several phenotypes known to have multiple associated methylation loci (age, sex, and smoking) in a discovery and a replication cohort. Among regions that were analysed by both methods, DMRPC identified 50% more genome-wide significant age-associated DMRs than coMethDMR. The replication rate for the loci that were identified by only DMRPC was higher than the rate for those that were identified by only coMethDMR (90% for DMRPC vs. 76% for coMethDMR). Furthermore, DMRPC identified replicable associations in regions of moderate between-CpG correlation which are typically not analysed by coMethDMR. For the analyses of sex and smoking, the advantage of DMRPC was less clear. In conclusion, DMRPC is a new powerful DMR discovery tool that retains power in genomic regions with moderate correlation across CpGs.
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影响因子：
7.1
作者：
通讯作者：
--
从头开始鉴定人基因组中差异甲基化区域。
影响因子：
3.9
作者：
Peters TJ;Buckley MJ;Statham AL;Pidsley R;Samaras K;V Lord R;Clark SJ;Molloy PL
通讯作者：
Molloy PL
人类血液和大脑衰老的一致性和不一致的DNA甲基化特征。
影响因子：
3.9
作者：
Farré P;Jones MJ;Meaney MJ;Emberly E;Turecki G;Kobor MS
通讯作者：
Kobor MS
影响因子：
3.7
作者：
Liu J;Morgan M;Hutchison K;Calhoun VD
通讯作者：
Calhoun VD
影响因子：
4.4
作者：
Affinito, Ornella;Palumbo, Domenico;Cocozza, Sergio
通讯作者：
Cocozza, Sergio