Chromatin-accessibility estimation from single-cell ATAC-seq data with scOpen

Zhijian Li, Christoph Kuppe, Susanne Ziegler, Mingbo Cheng, Nazanin Kabgani, Sylvia Menzel, Martin Zenke, Rafael Kramann () and Ivan G. Costa ()
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Zhijian Li: RWTH Aachen University Medical School
Christoph Kuppe: RWTH Aachen University Medical School
Susanne Ziegler: RWTH Aachen University Medical School
Mingbo Cheng: RWTH Aachen University Medical School
Nazanin Kabgani: RWTH Aachen University Medical School
Sylvia Menzel: RWTH Aachen University Medical School
Martin Zenke: RWTH Aachen University Medical School
Rafael Kramann: RWTH Aachen University Medical School
Ivan G. Costa: RWTH Aachen University Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract A major drawback of single-cell ATAC-seq (scATAC-seq) is its sparsity, i.e., open chromatin regions with no reads due to loss of DNA material during the scATAC-seq protocol. Here, we propose scOpen, a computational method based on regularized non-negative matrix factorization for imputing and quantifying the open chromatin status of regulatory regions from sparse scATAC-seq experiments. We show that scOpen improves crucial downstream analysis steps of scATAC-seq data as clustering, visualization, cis-regulatory DNA interactions, and delineation of regulatory features. We demonstrate the power of scOpen to dissect regulatory changes in the development of fibrosis in the kidney. This identifies a role of Runx1 and target genes by promoting fibroblast to myofibroblast differentiation driving kidney fibrosis.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26530-2

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DOI: 10.1038/s41467-021-26530-2

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