TABLE 2.
Comparison of single-cell epigenomic methods.
| Method | Advantages | Disadvantages |
| Methods for Single-cell DNA Methylation | ||
| scRBBS-seq | High coverage of the CpG islands | Low coverage of genome-wide sparse CpGs |
| scPBAT | High genome-wide CpG coverage; Low input requirement | Adaptor ligation bias |
| scCGI-seq | High coverage and consistency in CpG islands profiling | Low coverage of genome-wide sparse CpGs, Low-throughput |
| sci-MET | High-throughput and high alignment efficiency | Low coverage per cell |
| Methods for Single-cell Chromatin Accessibility | ||
| sci-ATAC-seq | High-throughput | Low coverage per cell |
| scATAC-seq (droplet-based) | High coverage of reads (in comparison with sci-ATAC-seq) | Low-throughput |
| scDNase-seq | High-sequencing resolution | Low throughput and mapping efficiency |
| Methods for Single-cell Histone Modifications | ||
| scCHIP-seq | High-throughput | Low coverage per cell |
| scDam-ID | No target-specific antibody required, suitable for identification of loose or indirect associations | Resolution limited by the frequency of methylation sites |
| scChIC-seq | High number of obtained unique reads per cell | Low throughput |
| scCUT&TAG | Cost-effective, High-throughput | Low number of unique reads |
| CoBATCH | High throughput, High number of obtained unique reads with low background | Unsuitable for repressive marks detection; non-specific cleavage of accessible regions |
| ACT-seq | High throughput, Simple workflow | Low number of unique reads; non-specific cleavage of accessible regions |
| scCHIL-seq | Low background | Time-consuming and complex workflow |
| Methods for Single-cell Nuclear Organization | ||
| scHi-C | High coverage per cell | Low-throughput |
| sciHi-C | High-throughput | Low depth per cell |
| Methods for Single-cell Multi-omics | ||
| scM&T-seq | High genome-wide CpG coverage | Medium throughput |
| scMT-seq | High coverage of the CpG islands | Low throughput, Low coverage of genome-wide sparse CpGs |
| scCOOL-seq | High coverage of the CpG islands and promoter regions | Low GCH coverage, high sequencing depth needed |
| iscCOOL-seq | Improved throughput and mapping efficiency | Low GCH coverage, high sequencing depth needed |
| scNMT-seq | Medium throughput | Low coverage of genome-wide CpGs |
| Methyl-HiC | Able to identify cell-type specific chromatin interactions | Low-throughput |
| sn-m3C-seq | Higher mapping efficiency than scNMT; cell-cell differences in chromatin conformation are hard to detect | Low throughput |