Preprocessing and Computational Analysis of Single-Cell Epigenomic Datasets

Methods Mol Biol. 2019:1935:187-202. doi: 10.1007/978-1-4939-9057-3_13.


Recent technological developments have enabled the characterization of the epigenetic landscape of single cells across a range of tissues in normal and diseased states and under various biological and chemical perturbations. While analysis of these profiles resembles methods from single-cell transcriptomic studies, unique challenges are associated with bioinformatics processing of single-cell epigenetic data, including a much larger (10-1,000×) feature set and significantly greater sparsity, requiring customized solutions. Here, we discuss the essentials of the computational methodology required for analyzing common single-cell epigenomic measurements for DNA methylation using bisulfite sequencing and open chromatin using ATAC-Seq.

Keywords: ATAC-seq; Bioinformatics; Bisulfite sequencing; DNA methylation; Epigenetics; Single-cell.

MeSH terms

  • Animals
  • Chromatin / genetics
  • Computational Biology / methods
  • DNA Methylation / genetics
  • Epigenesis, Genetic / genetics*
  • Epigenomics / methods
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Mice
  • Sequence Analysis, DNA / methods
  • Single-Cell Analysis / methods
  • Software


  • Chromatin