Systematic evaluation of genome-wide methylated DNA enrichment using a CpG island array

BMC Genomics

Research Article

Wei Dai¹  Zhong Sheng Sun¹  Liu Yang²  Kunlin Zhang³  Jing Wang³  Ximiao He³  Qian Zhao³ 

[1] Behavioral Genetics Center, Institute of Psychology, Chinese Academy of Sciences, 100101, Beijing, PR, China;Behavioral Genetics Center, Institute of Psychology, Chinese Academy of Sciences, 100101, Beijing, PR, China;Zhejiang University School of Medicine, 310058, Hangzhou, PR, China;Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 100101, Beijing, PR, China;

关键词: Bisulfite Sequencing;    Wellcome Trust Sanger Institute;    Differential Methylation Hybridization;    Enrichment Assay;    Methylcytosine Antibody;   

DOI  :  10.1186/1471-2164-12-10

 received in 2010-06-08, accepted in 2011-01-06,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundRecent progress in high-throughput technologies has greatly contributed to the development of DNA methylation profiling. Although there are several reports that describe methylome detection of whole genome bisulfite sequencing, the high cost and heavy demand on bioinformatics analysis prevents its extensive application. Thus, current strategies for the study of mammalian DNA methylomes is still based primarily on genome-wide methylated DNA enrichment combined with DNA microarray detection or sequencing. Methylated DNA enrichment is a key step in a microarray based genome-wide methylation profiling study, and even for future high-throughput sequencing based methylome analysis.ResultsIn order to evaluate the sensitivity and accuracy of methylated DNA enrichment, we investigated and optimized a number of important parameters to improve the performance of several enrichment assays, including differential methylation hybridization (DMH), microarray-based methylation assessment of single samples (MMASS), and methylated DNA immunoprecipitation (MeDIP). With advantages and disadvantages unique to each approach, we found that assays based on methylation-sensitive enzyme digestion and those based on immunoprecipitation detected different methylated DNA fragments, indicating that they are complementary in their relative ability to detect methylation differences.ConclusionsOur study provides the first comprehensive evaluation for widely used methodologies for methylated DNA enrichment, and could be helpful for developing a cost effective approach for DNA methylation profiling.

【 授权许可】

Unknown   
© Yang et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.