Pretreatment method Genome coverage NGS-based analysis Application Ref
Endonuclease digestion Moderate Methl-seq Assay a range of genomic elements; allowing a broader survey of regions than classic methylation studies limited to CpG islands and promoters [16]

HELP-seq Measurement of repetitive sequences, copy-number variability, allele-specific and smaller fragments (<50bp) ;Sensitivity of detection of hypomethylated loci [12,75]

MSCC Identification of the unmethylated region of a genome by pinpointing unmethylated CpGs at single base-pair resolution [13,14]

Affinity enrichment Moderate MeDIP-seq Generation of unbiased, cost-effective, and full-genome methylation levels without the limitations of restriction sites or CpG islands; [1,76]

MIRA-seq Analyze recovered or double-stranded methylated DNA on a genome-wide scale; Applicable to various clinical and diagnostic situations. [19]

MDB-seq Applied to any biological settings to identify differentially methylated regions at the genomic scale [18]

MethylCap-seq Detection of differentially methylated regions with high genome coverage; Detect DMRs in clinical samples [20,77]

Bisulfite conversion High BS-seq Sensitively measure cytosine methylation on a genome-wide scale within specific sequence contexts [48,78]

RRBS Analyze a limited number of gene promoters and regulatory sequence elements in a large number of samples; Analyzing and comparing genomic methylation patterns [11,28]

BSPP Focus sequencing on the most informative genomic regions ;exon capturing and SNP genotyping; Detecting methylation in large genomes

[29]

BC-seq Detect site-specific switches in methylation; Determine DNA methylation frequencies in CGIs sampled from a variety of genomic settings including promoters, exons, introns, and intergenic loci

[30]

Table 1: NGS-based technologies for detecting DNA methylation.