Establishing an analytic pipeline for genome-wide DNA methylation.
Establishing an analytic pipeline for genome-wide DNA methylation.
复制标题
建立用于全基因组DNA甲基化的分析管道。
DOI：
10.1186/s13148-016-0212-7
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发表时间：
2016
影响因子：
5.7
通讯作者：
York TP
中科院分区：
文献类型：
--
作者：
Wright ML;Dozmorov MG;Wolen AR;Jackson-Cook C;Starkweather AR;Lyon DE;York TP
在临床研究中调查DNA甲基化（DNAm）的研究需求增加，导致新的分析方法的发展，以提高这些研究结果解释的准确性和重现性。本文旨在为临床研究人员提供使用Illumina HumanMethylation 450K BeadChip研究全基因组DNAm的临床研究中常规应用的主要数据处理步骤的总结。在大多数研究中，采用DNAm分析的主要目标是鉴定表型组之间CpG位点的差异甲基化。实验设计考虑在开始时至关重要，以最大限度地减少与样品处理相关的因素的偏倚，并避免将实验变量与非生物批次效应混淆。虽然目前还没有事实上的标准方法来分析这些数据，我们回顾了几项研究建议处理DNAm数据的主要步骤。我们描述了可供临床研究人员处理、分析和解释DNA数据的几种变体。这些见解适用于大多数类型的全基因组DNAm阵列平台，并将适用于下一代DNAm阵列技术（例如，850K数组）。研究者遵循的DNA分析管道的选择应该以研究问题为指导，并得到最近发表的方法的支持。
The need for research investigating DNA methylation (DNAm) in clinical studies has increased, leading to the evolution of new analytic methods to improve accuracy and reproducibility of the interpretation of results from these studies. The purpose of this article is to provide clinical researchers with a summary of the major data processing steps routinely applied in clinical studies investigating genome-wide DNAm using the Illumina HumanMethylation 450K BeadChip. In most studies, the primary goal of employing DNAm analysis is to identify differential methylation at CpG sites among phenotypic groups. Experimental design considerations are crucial at the onset to minimize bias from factors related to sample processing and avoid confounding experimental variables with non-biological batch effects. Although there are currently no de facto standard methods for analyzing these data, we review the major steps in processing DNAm data recommended by several research studies. We describe several variations available for clinical researchers to process, analyze, and interpret DNAm data. These insights are applicable to most types of genome-wide DNAm array platforms and will be applicable for the next generation of DNAm array technologies (e.g., the 850K array). Selection of the DNAm analytic pipeline followed by investigators should be guided by the research question and supported by recently published methods.