Dataset Information

Modeling fragment counts improves single-cell ATAC-seq analysis.

ABSTRACT: Single-cell ATAC sequencing coverage in regulatory regions is typically binarized as an indicator of open chromatin. Here we show that binarization is an unnecessary step that neither improves goodness of fit, clustering, cell type identification nor batch integration. Fragment counts, but not read counts, should instead be modeled, which preserves quantitative regulatory information. These results have immediate implications for single-cell ATAC sequencing analysis.

SUBMITTER: Martens LD

PROVIDER: S-EPMC10776385 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Modeling fragment counts improves single-cell ATAC-seq analysis.

Martens Laura D LD Fischer David S DS Yépez Vicente A VA Theis Fabian J FJ Gagneur Julien J

Nature methods 20231204 1

Single-cell ATAC sequencing coverage in regulatory regions is typically binarized as an indicator of open chromatin. Here we show that binarization is an unnecessary step that neither improves goodness of fit, clustering, cell type identification nor batch integration. Fragment counts, but not read counts, should instead be modeled, which preserves quantitative regulatory information. These results have immediate implications for single-cell ATAC sequencing analysis. ...[more]

PMID: 38049697

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Project description:PurposeCorneal epithelial homeostasis is maintained by coordinated gene expression across distinct cell populations, but the gene regulatory programs underlying this cellular diversity remain to be characterized. Here we applied single-cell multi-omics analysis to delineate the gene regulatory profile of mouse corneal epithelial cells under normal homeostasis.MethodsSingle cells isolated from the cornea epithelium (with marginal conjunctiva) of adult mice were subjected to scRNA-seq and scATAC-seq using the 10×Genomics platform. Cell types were clustered by the graph-based visualization method uniform manifold approximation and projection and unbiased computational informatics analysis. The scRNA-seq and scATAC-seq datasets were integrated following the integration pipeline described in ArchR and Seurat.ResultsWe characterized diverse corneal epithelial cell types based on gene expression signatures and chromatin accessibility. We found that cell type-specific accessibility regions were mainly located at distal regions, suggesting essential roles of distal regulatory elements in determining corneal epithelial cell diversity. Trajectory analyses revealed a continuum of cell state transition and higher coordination between transcription factor (TF) motif accessibility and gene expression during corneal epithelial cell differentiation. By integrating transcriptomic and chromatin accessibility analysis, we identified cell type-specific and shared gene regulation programs. We also uncovered critical TFs driving corneal epithelial cell differentiation, such as nuclear factor I (NFI) family members, Rarg, Elf3. We found that nuclear factor-κB (NF-κB) family members were positive TFs in limbal cells and some superficial cells, but they were involved in regulating distinct biological processes.ConclusionsOur study presents a comprehensive gene regulatory landscape of mouse cornea epithelial cells, and provides valuable foundations for future investigation of corneal epithelial homeostasis in the context of cornea pathologies and regenerative medicine.

Dataset Information

Modeling fragment counts improves single-cell ATAC-seq analysis.

Publications

Modeling fragment counts improves single-cell ATAC-seq analysis.

Similar Datasets

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