2021
DOI: 10.1038/s41467-021-26530-2
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Chromatin-accessibility estimation from single-cell ATAC-seq data with scOpen

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-regulator… Show more

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Cited by 71 publications
(74 citation statements)
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References 81 publications
(164 reference statements)
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“…After choosing bins or peaks, some methods assign the feature counts based on the number of fragments that overlap with a region (fragment-based counting; e.g., Signac 1 and snapATAC 2 ), while others assign counts based on the number of insertions within the region (insertion-based counting; e.g., 10X cellranger ATAC 3 and ArchR 4 ). After feature counting, most methods convert the counts into a binary state of “open” or “closed” (e.g., snapATAC 2 , SCALE 5 , scOPEN 6 , MASETRO 7 , and cisTopic 8 ), while other retain quantitative count information, implying that single nucleus assays may contain quantitative information on nucleosome density or turnover (e.g., scABC 9 , chromVAR 10 , and ArchR 4 ).…”
Section: Mainmentioning
confidence: 99%
“…After choosing bins or peaks, some methods assign the feature counts based on the number of fragments that overlap with a region (fragment-based counting; e.g., Signac 1 and snapATAC 2 ), while others assign counts based on the number of insertions within the region (insertion-based counting; e.g., 10X cellranger ATAC 3 and ArchR 4 ). After feature counting, most methods convert the counts into a binary state of “open” or “closed” (e.g., snapATAC 2 , SCALE 5 , scOPEN 6 , MASETRO 7 , and cisTopic 8 ), while other retain quantitative count information, implying that single nucleus assays may contain quantitative information on nucleosome density or turnover (e.g., scABC 9 , chromVAR 10 , and ArchR 4 ).…”
Section: Mainmentioning
confidence: 99%
“…Suppose that we have one omics data with known cell types, and we want to analyze other omics data from the same population of cells without the label information. For instance, there are lots of work for RNA-seq clustering (9, 37, 38, 39), but little work for ATAC-seq clustering since the sparsity of ATAC-seq poses challenges on computational methods (40). Although obtaining scATAC-seq data from cells is becoming simpler and less expensive (41), getting the clustering information is not an easy task.…”
Section: Resultsmentioning
confidence: 99%
“…However, data produced by each modality has quite distinct characteristics regarding their numerical values (e.g. low counts for open chromatin and variable count values for RNA and proteins levels), dimensionality (dozens for proteins, tens of thousands for genes, hundreds of thousands for open chromatin) and levels of data sparsity ( Argelaguet et al , 2021 ; Li et al , 2021 ). These make the integrative analysis of multi-modal data a challenging task.…”
Section: Introductionmentioning
confidence: 99%