Chromatin-accessibility estimation from single-cell ATAC-seq data with scOpen
Nature Communications, vol. 12, pp. 6386
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.
Authors 9
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Zhijian Li Aachen Institute for Computational Genomics Joint Research Centre for Computational Biomedicine (JRC-COMBINE)
Affiliation as printed
Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen University Medical School, 52074, Aachen, Germany
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Christoph Kuppe Aachen Division of Nephrology and Clinical Immunology Institute of Experimental Medicine and Systems Biology
Affiliation as printed
Division of Nephrology and Clinical Immunology, RWTH Aachen University, 52074, Aachen, Germany
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany
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Mingbo Cheng Aachen Institute for Computational Genomics Joint Research Centre for Computational Biomedicine (JRC-COMBINE)
Affiliation as printed
Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen University Medical School, 52074, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany
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Affiliation as printed
Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, 52074, Aachen, Germany
Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany
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Rafael Kramann corresponding Aachen Division of Nephrology and Clinical Immunology Institute of Experimental Medicine and Systems Biology
Erasmus MC · RWTH Aachen University
Affiliation as printed
Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, 3015GD, Rotterdam, The Netherlands. rkramann@gmx.net
Division of Nephrology and Clinical Immunology, RWTH Aachen University, 52074, Aachen, Germany. rkramann@gmx.net
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany. rkramann@gmx.net
Division of Nephrology and Clinical Immunology, RWTH Aachen University, 52074, Aachen, Germany
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Ivan G. Costa corresponding Aachen Institute for Computational Genomics Joint Research Centre for Computational Biomedicine (JRC-COMBINE)
Affiliation as printed
Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen University Medical School, 52074, Aachen, Germany. ivan.costa@rwth-aachen.de
Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen University Medical School, 52074, Aachen, Germany
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