Table I.

Summary of microarray and next-generation sequencing assays in profiling DNA methylome.

	Restriction enzyme	Bisulfite modification	DNA precipitation	Advantages	Limitations	Ref.
Microarray-based methylation profiling
Endonuclease restriction-based microarray analysis
CHARM	McrBC	-	-	Identify hyper- or hypomethylated CpG sites	Moderate resolution; limit to restriction enzymes digested sites	22, 23
DMH	BstUI/HpaII	-	-			10, 11
HELP	HpaII/MspI	-	-			16, 17
MCAM	SmaI/XmaI	-	-			12
McrBC	McrBC	-	-			19, 20
MMASS	McrBC/cocktail	-	-			21
PMAD	HpaII/MspI	-	-			15
Bisulfite conversion-based microarray analysis
MSO	-	Yes	-	Cost efficiency	Moderate resolution	24
Bead array	-	Yes	-			28, 29
Affinity-based microarray analysis
MeDIP	-	-	Yes	Efficient assays to CGIs and repetitive sequences	Less sensitive to CpG poor sites	30
MIRA	-	-	Yes		Depending on MBD binding ability	32-34
Sequencing-based methylation profiling
BS-seq	-	Yes	-	High resolution	Higher cost at this stage	39
MethylC-Seq	-	Yes				44, 45
RRBS	MspI	Yes	-	Each sequencing-read contains at least one CpG site	Limit to restriction enzymes digested sites	41
HELP-seq	HpaII/MspI	-	-			17
Padlock probe	Could be	Yes	-	Quantify DNA methylation in a smaller genome fraction with high resolution at this stage	Limit to probes designing	42, 43
MeDIP-seq	-	-	-	Moderate resolution	Less sensitive to CpG poor sites	31