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Best practices for differential accessibility analysis in single-cell epigenomics

Author

Listed:
  • Alan Yue Yang Teo

    (EPFL/CHUV/UNIL
    Swiss Federal Institute of Technology (EPFL))

  • Jordan W. Squair

    (EPFL/CHUV/UNIL
    Swiss Federal Institute of Technology (EPFL)
    Lausanne University Hospital (CHUV) and University of Lausanne (UNIL))

  • Gregoire Courtine

    (EPFL/CHUV/UNIL
    Swiss Federal Institute of Technology (EPFL)
    Lausanne University Hospital (CHUV) and University of Lausanne (UNIL))

  • Michael A. Skinnider

    (EPFL/CHUV/UNIL
    Swiss Federal Institute of Technology (EPFL)
    Princeton University
    Princeton University)

Abstract

Differential accessibility (DA) analysis of single-cell epigenomics data enables the discovery of regulatory programs that establish cell type identity and steer responses to physiological and pathophysiological perturbations. While many statistical methods to identify DA regions have been developed, the principles that determine the performance of these methods remain unclear. As a result, there is no consensus on the most appropriate statistical methods for DA analysis of single-cell epigenomics data. Here, we present a systematic evaluation of statistical methods that have been applied to identify DA regions in single-cell ATAC-seq (scATAC-seq) data. We leverage a compendium of scATAC-seq experiments with matching bulk ATAC-seq or scRNA-seq in order to assess the accuracy, bias, robustness, and scalability of each statistical method. The structure of our experiments also provides the opportunity to define best practices for the analysis of scATAC-seq data beyond DA itself. We leverage this understanding to develop an R package implementing these best practices.

Suggested Citation

  • Alan Yue Yang Teo & Jordan W. Squair & Gregoire Courtine & Michael A. Skinnider, 2024. "Best practices for differential accessibility analysis in single-cell epigenomics," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53089-5
    DOI: 10.1038/s41467-024-53089-5
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