| 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] |