Table 1.
Summary of existing methods for genomic mapping of DNA modifications
| Modifications | Method | Resol’n | Method | Basis | Limitation | Ref |
|---|---|---|---|---|---|---|
| 5mC | Bisulfite reaction based | 1 nt | BS-seq | Differential deamination of C and 5mC to U | Specific to 5mC | (22) |
| 5mC, 5hmC | oxBS-Seq | 5hmC converted to uracil | Specific to 5hmC | (23) | ||
| 6mA, 4mC, 5mC et al. | Third generation sequencing | 1 nt | SMRT sequencing | Detection during sequencing | Sensitivity, specificity | (4,27) |
| 5mC; 6mA | Nanopore sequencing | Detection during sequencing | Noise, sensitivity, specificity | (42) | ||
| Methylation status of CpG islands | DNA microarray based | Low | CpG island microarray | Restriction enzyme digestion; microarray | Methylation-sensitive restriction enzymes | (20) |
| Methylation | MeDIP-on-Chip | IP, hybridize of DNA on microarray | Modification-specific antibody | (21) | ||
| 5mC and 5hmC | Chemical-labeling for NGS sequencing | 1 nt | TAPS | Oxidation of 5mC/5hmC to 5caC, reduce to dihydrouracil | Specific to 5mC and 5hmC | (24) |
| 8-oxoG | ∼150 nt | OG-seq | Derivatize 8-oxoG with biotin | Specific to 8-oxoG | (6) | |
| AP sites | 1 nt | snAP-seq | Chemical labelling of AP site with biotin | Specific to AP sites | (25) | |
| 8-oxoG | 1 nt | Click-code-Seq | BER excision; click chemistry | DNA 3′-OH end required | (31) | |
| UV-induced DNA lesions | Antibody-enrichment for NGS sequencing | 1 nt | XR-seq | Damaged DNA IP, NGS | Lesion-specific antibody | (26) |
| 8-oxoG | ∼150 nt | OxiDIP-Seq | 8-oxoG IP for NGS sequencing | 8-oxoG -specific antibody | (12) | |
| 5ghmC, 5hmC | Modif’n-dependent restriction enzyme | 3∼5 nt | Aba-seq | AbaSI recognizes 5ghmC and 5hmC | Limited to a narrow spectrum of modifications | (29) |
| Uracil, pyrimidine dimer | BER enzyme excision | <1 nt | Excision-seq | BER enzyme excision, NGS | Very low sensitivty; low-resolution | (11) |
| Single-strand breaks | TdT-labeling | 1 nt | SSiNGLe | TdT-labeling of strand break, NGS | T modific’n not detected; limited to SSB only | (36) |
| Single-strand breaks | Nick translation | ?>1 nt | SSB-seq | Nick translation with biotin dNTP, IP, NGS | Uncontrolled nuclease S1 trimming; SSB only | (35) |
| Double-strand breaks | TdT-labeling | ?>10 nt | DSB-seq | TdT-tailing with labeled dNTP, IP, NGS | T modific’n not detected; nuclease S1 trimming; SSB only | (35) |