Bisulfite-free epigenomics and genomics of single cells through methylation-sensitive restriction
Christoph Niemöller, Julius Wehrle, Julian Riba, Rainer Claus, Nathalie Renz, Janika Rhein, Sabine Bleul, Juliane M. Stosch, Justus Duyster, Christoph Plass, Pavlo Lutsik, Daniel B. Lipka, Michael Lübbert, Heiko Becker
Abstract
Single-cell multi-omics are powerful means to study cell-to-cell heterogeneity. Here, we present a single-tube, bisulfite-free method for the simultaneous, genome-wide analysis of DNA methylation and genetic variants in single cells: epigenomics and genomics of single cells analyzed by restriction (epi-gSCAR). By applying this method, we obtained DNA methylation measurements of up to 506,063 CpGs and up to 1,244,188 single-nucleotide variants from single acute myeloid leukemia-derived cells. We demonstrate that epi-gSCAR generates accurate and reproducible measurements of DNA methylation and allows to differentiate between cell lines based on the DNA methylation and genetic profiles.