Modeling fragment counts improves single-cell ATAC-seq analysis

Nat Methods. 2024 Jan;21(1):28-31. doi: 10.1038/s41592-023-02112-6. Epub 2023 Dec 4.

Abstract

Single-cell ATAC sequencing coverage in regulatory regions is typically binarized as an indicator of open chromatin. Here we show that binarization is an unnecessary step that neither improves goodness of fit, clustering, cell type identification nor batch integration. Fragment counts, but not read counts, should instead be modeled, which preserves quantitative regulatory information. These results have immediate implications for single-cell ATAC sequencing analysis.

MeSH terms

  • Chromatin / genetics
  • Chromatin Immunoprecipitation Sequencing*
  • High-Throughput Nucleotide Sequencing* / methods
  • Sequence Analysis, DNA / methods
  • Single-Cell Analysis

Substances

  • Chromatin