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Cells whose accessibility landscape has been profiled with scATAC-seq cannot readily be annotated to a particular cell type. In fact, annotating cell-types in scATAC-seq data is a challenging task since, unlike in scRNA-seq data, we lack knowledge of 'marker regions' which could be used for cell-type annotation. Current annotation methods typically translate accessibility to expression space and rely on gene expression patterns. We propose a novel approach, scATAcat, that leverages characterized bulk ATAC-seq data as prototypes to annotate scATAC-seq data. To mitigate the inherent sparsity of single-cell data, we aggregate cells that belong to the same cluster and create pseudobulk. To demonstrate the feasibility of our approach we collected a number of datasets with respective annotations to quantify the results and evaluate performance for scATAcat. scATAcat is available as a python package at https://github.com/aybugealtay/scATAcat.
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http://dx.doi.org/10.1093/nargab/lqae135 | DOI Listing |
Phytomedicine
August 2025
Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:
Background: Traditional Chinese medicines (TCMs) have a long-standing history and diverse applications. However, their complex multi-component compositions and intricate mechanisms of action pose significant challenges for modern scientific investigation. Addressing these complexities requires advanced techniques capable of dissecting cellular and molecular interactions with high resolution.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
School of Mathematics, Shandong University, Jinan, Shandong, 250100, China.
scATAC-seq enables the detailed exploration of epigenetic variations across various cell clusters, providing complementary insights to scRNA-seq. However, its extreme sparsity and high dimensionality pose significant challenges for cell type annotation. Transfer learning can extract key features from well-annotated data to assist in annotating target data, thereby improving annotation accuracy.
View Article and Find Full Text PDFBioinformatics
August 2025
School of Mathematics, Harbin Institute of Technology, Harbin, 150000, China.
Summary: Identifying cell states associated with disease progression or experimental perturbations from single-cell Assay for Transposase Accessible Chromatin using sequencing (scATAC-seq) data is critical for unraveling disease pathogenesis. However, the high dimensionality, extreme sparsity, and nearly binary nature of scATAC-seq data pose significant challenges. Here, we present reDA, a cluster-free computational framework that performs differential abundance testing based on the random walk with restart.
View Article and Find Full Text PDFBMC Genomics
August 2025
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Chongqing, 400038, China.
Background: Single-cell RNA sequencing analysis faces critical challenges including high dimensionality, sparsity, and complex topological relationships between cells. Current methods struggle to simultaneously preserve global structure, model cellular dynamics, and handle technical noise effectively.
Results: We present GNODEVAE, a novel architecture integrating Graph Attention Networks (GAT), Neural Ordinary Differential Equations (NODE), and Variational Autoencoders (VAE) for comprehensive single-cell analysis.
PNAS Nexus
August 2025
Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences (RIMLS), P.O. Box 9101, Nijmegen 6500HB, The Netherlands.
The cornea, a transparent tissue composed of multiple layers, allows light to enter the eye. Several single-cell RNA-seq (scRNA-seq) analyses have been performed to explore the cell states and to understand the cellular composition of the human cornea. However, inconsistences in cell state annotations between these studies complicate the application of these findings in corneal studies.
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