Cited by 1,769Single-cell and spatial transcriptomicsGenomics and Chromatin DynamicsChromatin Remodeling and Cancer

Single-cell chromatin state analysis with Signac

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Stuart, Tim, Srivastava, Avi, Madad, Shaista, Lareau, Caleb A., Satija, Rahul·2021·Nature Methods

Abstract

The recent development of experimental methods for measuring chromatin state at single-cell resolution has created a need for computational tools capable of analyzing these datasets. Here we developed Signac, a comprehensive toolkit for the analysis of single-cell chromatin data. Signac enables an end-to-end analysis of single-cell chromatin data, including peak calling, quantification, quality control, dimension reduction, clustering, integration with single-cell gene expression datasets, DNA motif analysis and interactive visualization. Through its seamless compatibility with the Seurat package, Signac facilitates the analysis of diverse multimodal single-cell chromatin data, including datasets that co-assay DNA accessibility with gene expression, protein abundance and mitochondrial genotype. We demonstrate scaling of the Signac framework to analyze datasets containing over 700,000 cells.

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  • Chromatin accessibility of CREs associated with a gene can be summarized into gene activity scores by summing counts within genes and a certain distance upstream of the TSS.

    “This can be achieved by summing up counts within genes and a certain distance upstream of the TSS136,143,150.”

    From Best practices for single-cell analysis across modalities (2023) · cites this paper as [143]

  • Correlation-based methods are used to link peaks to genes within clusters to identify potential CREs.

    “To identify potential CREs, correlation-based methods are used to link peaks to genes within clusters of cells140,143,156.”

    From Best practices for single-cell analysis across modalities (2023) · cites this paper as [143]

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Authors
Stuart, T., Srivastava, A., Madad, S., Lareau, C. A., & Satija, R.
Affiliations
  • New York Genome Center (US)
  • Stanford University (US)
Corresponding author
  • Stuart, Tim
  • Satija, Rahul
Venue
Nature Methods
Published
2021-11
Volume
18
Issue
11
Pages
1333-1341
ISSN
  • 1548-7091 (ISSN-L)
  • 1548-7105
OpenAlex
W3210860076
Cited by
1,769
References
82
Citations by year
2026: 449 · 2025: 491 · 2024: 384 · 2023: 277 · 2022: 159 · 2021: 9
FWCI
67.26
Type
journal article
Language
en
Open access
Locations
  • Nature Methods (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (K99HG011489-01, DP2HG009623-01)
  • U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OT2OD026673-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
Signac, chromatin accessibility, peak calling, multimodal single-cell data, dimensionality reduction, clustering, quality control, mitochondrial genotype
MeSH terms
Bone Marrow Cells, Chromatin, Humans, Leukocytes, Mononuclear, Mitochondria, Software, Sequence Analysis, DNA, Computational Biology, Gene Expression Profiling, Single-Cell Analysis

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