Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
PLoS One. 2012;7(11):e50233. doi: 10.1371/journal.pone.0050233. Epub 2012 Nov 29.
DNA methylation is one of the most studied epigenetic marks in the human genome, with the result that the desire to map the human methylome has driven the development of several methods to map DNA methylation on a genomic scale. Our study presents the first comparison of two of these techniques - the targeted approach of the Infinium HumanMethylation450 BeadChip® with the immunoprecipitation and sequencing-based method, MeDIP-seq. Both methods were initially validated with respect to bisulfite sequencing as the gold standard and then assessed in terms of coverage, resolution and accuracy. The regions of the methylome that can be assayed by both methods and those that can only be assayed by one method were determined and the discovery of differentially methylated regions (DMRs) by both techniques was examined. Our results show that the Infinium HumanMethylation450 BeadChip® and MeDIP-seq show a good positive correlation (Spearman correlation of 0.68) on a genome-wide scale and can both be used successfully to determine differentially methylated loci in RefSeq genes, CpG islands, shores and shelves. MeDIP-seq however, allows a wider interrogation of methylated regions of the human genome, including thousands of non-RefSeq genes and repetitive elements, all of which may be of importance in disease. In our study MeDIP-seq allowed the detection of 15,709 differentially methylated regions, nearly twice as many as the array-based method (8070), which may result in a more comprehensive study of the methylome.
DNA 甲基化是人类基因组中研究最多的表观遗传标记之一，因此，人们渴望绘制人类甲基组，这推动了几种在基因组范围内绘制 DNA 甲基化图谱的方法的发展。我们的研究首次比较了这两种技术——靶向方法的 Infinium HumanMethylation450 BeadChip®与基于免疫沉淀和测序的方法 MeDIP-seq。这两种方法最初都针对亚硫酸氢盐测序作为金标准进行了验证，然后从覆盖度、分辨率和准确性方面进行了评估。确定了两种方法都可以检测的甲基组区域和只能用一种方法检测的区域，并检查了两种技术发现的差异甲基化区域（DMRs）。我们的研究结果表明，Infinium HumanMethylation450 BeadChip®和 MeDIP-seq 在全基因组范围内具有良好的正相关性（Spearman 相关系数为 0.68），并且都可以成功地确定 RefSeq 基因、CpG 岛、shore 和 shelf 中差异甲基化的基因座。然而，MeDIP-seq 可以更广泛地检测人类基因组中甲基化的区域，包括数千个非 RefSeq 基因和重复元件，所有这些在疾病中都可能很重要。在我们的研究中，MeDIP-seq 检测到了 15709 个差异甲基化区域，几乎是基于阵列方法（8070）的两倍，这可能会更全面地研究甲基组。
