Cited by 455Single-cell and spatial transcriptomicsGenomics and Chromatin DynamicsGene Regulatory Network Analysis

Comprehensive analysis of single cell ATAC-seq data with SnapATAC

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Fang, Rongxin, Preissl, Sebastian, Li, Yang, Hou, Xiaomeng, Lucero, Jacinta, Wang, Xinxin, Motamedi, Amir, Shiau, Andrew K. +8 more·2021·Nature Communications

Published version of a preprint

Abstract

Identification of the cis-regulatory elements controlling cell-type specific gene expression patterns is essential for understanding the origin of cellular diversity. Conventional assays to map regulatory elements via open chromatin analysis of primary tissues is hindered by sample heterogeneity. Single cell analysis of accessible chromatin (scATAC-seq) can overcome this limitation. However, the high-level noise of each single cell profile and the large volume of data pose unique computational challenges. Here, we introduce SnapATAC, a software package for analyzing scATAC-seq datasets. SnapATAC dissects cellular heterogeneity in an unbiased manner and map the trajectories of cellular states. Using the Nyström method, SnapATAC can process data from up to a million cells. Furthermore, SnapATAC incorporates existing tools into a comprehensive package for analyzing single cell ATAC-seq dataset. As demonstration of its utility, SnapATAC is applied to 55,592 single-nucleus ATAC-seq profiles from the mouse secondary motor cortex. The analysis reveals ~370,000 candidate regulatory elements in 31 distinct cell populations in this brain region and inferred candidate cell-type specific transcriptional regulators.

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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 [136]

  • Binarization of peaks is the most common normalization strategy for scATAC-seq data.

    “In scATAC-seq data, the most common normalization strategy is binarization of peaks136,140,141.”

    From Best practices for single-cell analysis across modalities (2023) · cites this paper as [136]

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Research works printed but not linked: 1

  1. [51]Li, M., Kwok, J. T. & Lu, B.-L. Making large-scale Nyström approximation possible. in Proc. 27th International Conference on Machine Learning 631–638 (2010).

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Authors
Fang, R., Preissl, S., Li, Y., Hou, X., Lucero, J., Wang, X., Motamedi, A., Shiau, A. K., Zhou, X., Xie, F., Mukamel, E. A., Zhang, K., Zhang, Y., Behrens, M. M., Ecker, J. R., & Ren, B.
Affiliations
  • Harvard University (US)
  • University of California San Diego (US)
  • Ludwig Cancer Research (US)
  • Salk Institute for Biological Studies (US)
  • Ludwig Cancer Research (BE)
Corresponding author
Ren, Bing
Venue
Nature Communications
Published
2021-02-26
Volume
12
Issue
1
Pages
1337-1337
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3133082627
Cited by
455
References
58
Citations by year
2026: 41 · 2025: 63 · 2024: 94 · 2023: 78 · 2022: 88 · 2021: 65 · 2020: 17 · 2019: 9
FWCI
27.39
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • Howard Hughes Medical Institute
  • Damon Runyon Cancer Research Foundation
  • National Institutes of Health
  • University of California, San Diego
  • National Institute of Mental Health (U19MH114831)
  • National Cancer Institute (K99CA252020, P30CA014195)
  • School of Medicine, University of California, San Diego
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 › Gene Regulatory Network Analysis
Keywords
single-cell ATAC-seq, cis-regulatory elements, open chromatin, cellular heterogeneity, cell type-specific gene expression, single-nucleus ATAC-seq, secondary motor cortex, transcription factors, cell trajectory inference, Nyström method, software package
MeSH terms
Chromatin Immunoprecipitation Sequencing, Animals, Chromatin, Male, Mice, Inbred C57BL, Motor Cortex, Sequence Analysis, DNA, Computational Biology, Mice, Epigenomics, Single-Cell Analysis

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