title: Systematic evaluation of genome-wide methylated DNA enrichment using a CpG island array.
abstract: BACKGROUND
  Recent 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 100101 Beijing, PR China. wangjing@psych.ac.cn
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Kunlin
authors.initials: K
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Ximiao
authors.initials: X
authors.lastname: He
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Zhong Sheng
authors.initials: ZS
authors.lastname: Sun
mesh_terms: D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000191:economics / Q000379:methods*; D012680:Sensitivity and Specificity