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*, Ivan G. Costa*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

44 Citations (Scopus)
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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.

Original languageEnglish
Article number6386
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
This work was funded by grants of the Interdisciplinary Center for Clinical Research (IZKF) Aachen, RWTH Aachen University Medical School, Aachen, Germany and by the Deutsche Forschungsgemeinschaft (DFG-GE 2811/3) to I.G.C. and (DFG SFB/TRR57 P30, SFB/ TRR219 P5) and a Grant of the European Research Council (ERC-StG 677448) to R.K. and by the Bundesministerium für Bildung und Forschung (BMBF e:Med Consortia Fibromap) to I.G.C. and R.K. C.K. was partly funded by the clinician-scientist program of the German Society of Internal Medicine (DGIM) and a Gerok position of the DFG SFB/TRR 219, P5. Simulations were performed with computing resources granted by ITC RWTH Aachen University under projects rwth0233 and rwth0429. We thank the team of the IZKF Aachen Genomics Core facility for sequencing experiments.

Publisher Copyright:
© 2021, The Author(s).

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