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sciMET-cap: high-throughput single-cell methylation analysis with a reduced sequencing burden

  • Sonia N. Acharya,
  • Ruth V. Nichols,
  • Lauren E. Rylaarsdam,
  • Brendan L. O’Connell,
  • Theodore P. Braun,
  • Andrew C. Adey

摘要

DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap). Accumulated off-target coverage enables genome-wide differentially methylated region (DMR) calling for clusters with as few as 115 cells. We characterize sciMET-cap on human PBMCs and brain (middle frontal gyrus).