Table 1.

Brief summary of single-cell DNA methylation profiling methods ¹.

Basis	PBAT	Single-Cell Method	Related Method 2	Advanced Strategy 3	Ref.
RRBS	No	scRRBS	None	Single-tube reaction, tRNA carrier	[46]
		Q-RRBS	scRRBS	UMI adaptor	[47]
		MID-RRBS	None	Microfluidics	[41]
		scTrio-seq	scRRBS, scRNA-seq	Multi-omics (RNA, CNV)	[48]
		scMT-seq	scRRBS, Smart-seq2	Multi-omics (RNA)	[49]
WGBS	Yes 4	scBS-seq	None	Single-tube reaction, Preamplification, SPRI bead	[50]
		scPBAT	None	Non-preamplification (repeat-specialized)	[51]
		scWGBS	None	Non-preamplification	[52]
		snmC-seq2 5	snmC-seq	Single-strand library preparation method	[53]
		sci-MET	None	Transposase tagmentation, combinatorial indexing	[54]
		scTrio-seq2	scBS-seq, scTrio-seq	Multi-omics (RNA, CNV)	[55]
		scM&T-seq	scBS-seq, G&T-seq	Multi-omics (RNA)	[56]
		scNMT-seq	scM&T-seq, NOMe-seq	Multi-omics (RNA, chromatin accessibility)	[57]
		iscCOOL-seq 5	scCOOL-seq, NOMe-seq	Multi-omics (chromatin accessibility, CNV, ploidy)	[58]
		scNOMe-seq	NOMe-seq	Multi-omics (chromatin accessibility)	[59]
MSRE	No	scCGI-seq	None	MDA	[60]

¹ This table originated from another review paper (Karemaker and Vermeulen, 2018) [61] and has been reduced, reorganized, and updated to fit our review scope. The original review contains descriptions of various methods that are not within the scope of this paper. ² If there is no mention of a related method in the paper, even if the method is similar to other methods, the classification is None. ³ Because DNA methylation is indicated by default, it is not separately indicated in multi-omics. ⁴ If there was an adaptor tagging step after bisulfite conversion, it was classified as PBAT. ⁵ Because the improved method and the original method are similar in basic purpose, only the most recent method is indicated. PBAT: post-bisulfite adaptor tagging; RRBS: reduced representation bisulfite sequencing; Q: quantitative; sc: single-cell; UMI: unique molecular identifier; MID: microfluidic diffusion; trio, triple omics; WGBS: whole-genome bisulfite sequencing; CNV: copy number variation; MT: methylome and transcriptome; SPRI: solid-phase reversible immobilization; M&T: methylation and transcriptome; G&T: genome and transcriptome; NMT: nucleosome, methylation, and transcription; NOMe: nucleosome occupancy and methylome; iscCOOL-seq: improved single-cell chromatin overall omic-scale landscape sequencing; sci-MET: single-cell indexing for methylation analysis; MSRE: methylation-sensitive restriction enzymes; CGI: CpG island; MDA: multiple displacement amplification.