Single-cell DNA methylation profiling currently suffers from excessive noise and/or limited cellular throughput. We developed scTAM-seq, a targeted bisulfite-free method for profiling up to 650 CpGs in up to 10,000 cells per experiment, with a dropout rate as low as 7%. We demonstrate that scTAM-seq can resolve DNA methylation dynamics across B-cell differentiation in blood and bone marrow, identifying intermediate differentiation states that were previously masked. scTAM-seq additionally queries surface-protein expression, thus enabling integration of single-cell DNA methylation information with cell atlas data. In summary, scTAM-seq is a high-throughput, high-confidence method for analyzing DNA methylation at single-CpG resolution across thousands of single cells.
CITATION STYLE
Bianchi, A., Scherer, M., Zaurin, R., Quililan, K., Velten, L., & Beekman, R. (2022). scTAM-seq enables targeted high-confidence analysis of DNA methylation in single cells. Genome Biology, 23(1). https://doi.org/10.1186/s13059-022-02796-7
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