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

A major drawback of single cell ATAC (scATAC) is its sparsity, i.e. open chromatin regions with no reads due to loss of DNA material during the scATAC-seq protocol. We propose scOpen, a computational method for imputing and quantifying the open chromatin status of regulatory regions from sparse scATAC-seq experiments. We show that scOpen improves crucial down-stream analysis steps of scATAC-seq data as clustering, visualisation, 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 identified a novel role of Runx1 and target genes by promoting fibroblast to myofibroblast differentiation driving kidney fibrosis.