Farlik, M. et al. Cell Rep. 10, 1386–1397 (2015).

Treating DNA with bisulfite before sequencing enables the detection of methylated cytosine residues across the genome. The method is powerful but also damages DNA, making its application to small samples very challenging. Farlik et al. ligate sequencing adaptors after chemical treatment for whole-genome bisulfite sequencing of small samples (μWGBS) and single cells (scWGBS). The researchers gear the method toward profiling large numbers of cells at low sequencing coverage and include a computational tool for extracting epigenetic states from sparse methylation data. They studied in vitro differentiation of human blood and mouse stem cells, as well as the effect of the drug azacytidine on an erythroleukemia-derived cell line, and showed that their bioinformatic approach can gain statistical power by combining signal from multiple genomic regions such as regulatory elements.