Table 2.

Summary and comparison of the characteristics of global DNA methylation methods

Attributes	Affinity enrichment-based	Restriction enzyme-based	Bisulfite conversion
Assays	MeDIP-seq [81], MBD-seq [70]	HELP-seq [64], MRE-seq [65]	WGBS [46], RRBS [67]
Resolution	Approximately 150 bp	Single base	Single base
Regions covered	Approximately 23 million CpGs	Approximately 2 million CpGs	>28 million CpGs (WGBS) approximately 2 million CpGs (85% of CpG islands and 60% of promoters; RRBS)
Advantages	Allows for rapid and specific assessment of the average methylation levels of large DNA regions, No mutation introduced, Cost-effective	High sensitivity with lower costs, Simple approach, Cost-effective	Evaluates methylation status of every CpG site
Limitations	Limited by the quality and specificity of the antibody or protein, Bias into hyper-methylated regions, Unpredictable absolute methylation level, No information on separate CpG dinucleotides	Restricted to restriction enzyme-digestion sites, Requires large amount, high purity, and integrity of DNA	High cost, High DNA input, DNA damage after bisulfite conversion

MeDIP-seq, methylated DNA immunoprecipitation and sequencing; MBD-seq, methylated-CpG-binding protein sequencing; HELP-seq, HpaII tiny fragments Enrichment by Ligation-mediated PCR; MRE-seq, methylation-sensitive restriction enzyme; WGBS, whole-genome bisulfite sequencing; RRBS, reduced-representation bisulfite sequencing; CpGs, cytosine phosphate guanine.