Another general limitation of most extant epigenomic methods is that the vast majority of such assays are based on ensemble measurements in which the measurement of chromatin state reports on the average chromatin state for thousands or millions of cells. As decomposition of ensembles into individual entities has provided foundational insights into single-molecule biochemistry, single-cell gene regulation, and many other fields, it is expected that single-cell assays for chromatin will be required to illuminate several key questions in chromatin structure. In general, one may consider two broad methods of gaining insight into single-cell behavior of chromatin—computational deconvolution of ensemble measurements into constituent subpopulations (Houseman et al. 2015) and experimental analysis of single cells. We focus below on experimental approaches to single-cell epigenomics.
