Table 1.

Comparison of typical analyses performed on single-cell and bulk methylome sequencing data

Analysis	Bulk tissue	Single cell
Tissue- or cell-specific epigenome	Lineage relationship of the major constituent cell states of tissues	Differentiation trajectory of single cells and cell states
Cell composition analysis	Top-down cell composition analysis of convoluted tissue signals	Bottom-up cell composition analysis focusing on rare cell types
DNA copy number annotation	Weighted average DNA copy number from the whole cell population	DNA copy numbers of each cell and its heterogeneity
DNA copy number on sex chromosomes	Sex inference and sex chromosome abnormality of the whole individual	Sex chromosome epigenetic mosaicisms across cell types
Primary tumor epigenetic alteration	Focus on tumor vs. normal epigenetic differences such as global hypomethylation	Distinguish cell-autonomous epigenetic changes in individual tumor cells
Tumor cell evolution history	Compare the epigenome of tumor at multiple sites (e.g., primary vs. metastatic)	Resolve clonal evolution history of tumor cells
Cell cycle	Compute the fraction of cells at different cell cycle stages	Determine cell cycle stage of individual cells
Epigenome–transcriptome association	Epigenome–transcriptome associations influenced by cell type variation	Epigenome–transcriptome associations across cells of the same cell type