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Evaluation of affinity-based genome-wide DNA methylation data: Effects of CpG density, amplification bias, and copy number variation

tlexander 添加于 2010-11-14 23:57 | 1378 次阅读 | 0 个评论

作者
Robinson MD, Stirzaker C, Statham AL, Coolen MW, Song JZ, Nair SS, Strbenac D, Speed TP, Clark SJ
摘要
DNA methylation is an essential epigenetic modification that plays a key role associated with the regulation of gene expression during differentiation, but in disease states such as cancer, the DNA methylation landscape is often deregulated. There are now numerous technologies available to interrogate the DNA methylation status of CpG sites in a targeted or genome-wide fashion, but each method, due to intrinsic biases, potentially interrogates different fractions of the genome. In this study, we compare the affinity-purification of methylated DNA between two popular genome-wide techniques, methylated DNA immunoprecipitation (MeDIP) and methyl-CpG binding domain-based capture (MBDCap). and show that each technique operates in a different domain of the CpG density landscape. We explored the effect of whole-genome amplification and illustrate that it can reduce sensitivity for detecting DNA methylation in GC-rich regions of the genome. By using MBDCap, we compare and contrast microarray- and sequencing-based readouts and highlight the impact that copy number variation (CNV) can make in differential comparisons of methylomes. These studies reveal that the analysis of DNA methylation data and genome coverage is highly dependent on the method employed, and consideration must be made in light of the GC content, the extent of DNA amplification, and the copy number.
详细资料
- 文献种类: Journal Article
- 期刊名称: Genome Research
- 期刊缩写: Genome Res
- 期卷页: 2010年
- 地址: Epigenetics Laboratory, Cancer Research Program, Garvan Institute of Medical Research, Sydney 2010, New South Wales, Australia
- ISBN: 1088-9051
- 备注:PMID:21045081
学科领域生物医药 » 基础医学
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