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SnapATAC: A Comprehensive Analysis Package for Single Cell ATAC-seq

Rongxin Fang, Sebastian Preissl, Yang Li, Xiaomeng Hou, Jacinta Lucero, Xinxin Wang, Amir Motamedi, Andrew K. Shiau, Xinzhu Zhou, Fangming Xie, Eran A. Mukamel, Kai Zhang, Yanxiao Zhang, M. Margarita Behrens, Joseph R. Ecker, Bing Ren
doi: https://doi.org/10.1101/615179
Rongxin Fang
1Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA 92093, USA
2Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
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Sebastian Preissl
3Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
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Yang Li
2Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
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Xiaomeng Hou
3Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
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Jacinta Lucero
4The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
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Xinxin Wang
3Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
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Amir Motamedi
5Small Molecule Discovery Program, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
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Andrew K. Shiau
5Small Molecule Discovery Program, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
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Xinzhu Zhou
6Biomedical Science Graduate Program, University of California San Diego, La Jolla, CA 92093, USA
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Fangming Xie
7Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA
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Eran A. Mukamel
7Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA
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Kai Zhang
2Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
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Yanxiao Zhang
2Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
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M. Margarita Behrens
4The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
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Joseph R. Ecker
4The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
8Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
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Bing Ren
2Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
3Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
9Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, UCSD Moores Cancer Center, La Jolla, CA 92093, USA
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  • For correspondence: biren{at}ucsd.edu
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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 heterogeneity of the samples. Single cell analysis of transposase-accessible chromatin (scATAC-seq) can overcome this limitation. However, the high-level noise of each single cell profile and the large volumes of data could pose unique computational challenges. Here, we introduce SnapATAC, a software package for analyzing scATAC-seq datasets. SnapATAC can efficiently dissect cellular heterogeneity in an unbiased manner and map the trajectories of cellular states. Using the Nyström method, a sampling technique that generates the low rank embedding for large-scale dataset, 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 was applied to 55,592 single-nucleus ATAC-seq profiles from the mouse secondary motor cortex. The analysis revealed ∼370,000 candidate regulatory elements in 31 distinct cell populations in this brain region and inferred candidate transcriptional regulators in each of the cell types.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 17, 2020.
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SnapATAC: A Comprehensive Analysis Package for Single Cell ATAC-seq
Rongxin Fang, Sebastian Preissl, Yang Li, Xiaomeng Hou, Jacinta Lucero, Xinxin Wang, Amir Motamedi, Andrew K. Shiau, Xinzhu Zhou, Fangming Xie, Eran A. Mukamel, Kai Zhang, Yanxiao Zhang, M. Margarita Behrens, Joseph R. Ecker, Bing Ren
bioRxiv 615179; doi: https://doi.org/10.1101/615179
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SnapATAC: A Comprehensive Analysis Package for Single Cell ATAC-seq
Rongxin Fang, Sebastian Preissl, Yang Li, Xiaomeng Hou, Jacinta Lucero, Xinxin Wang, Amir Motamedi, Andrew K. Shiau, Xinzhu Zhou, Fangming Xie, Eran A. Mukamel, Kai Zhang, Yanxiao Zhang, M. Margarita Behrens, Joseph R. Ecker, Bing Ren
bioRxiv 615179; doi: https://doi.org/10.1101/615179

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