Work

Capturing cell-type-specific activities of cis-regulatory elements from peak-based single-cell ATAC-seq

Year: 2025

Type: article

Abstract: Single-cell ATAC sequencing (scATAC-seq), a state-of-the-art genomic technique designed to map chromatin accessibility at the single-cell level, presents unique analytical challenges due to limited sampling and data sparsity. In this study, we use case studies to highlight the limitations of conventional peak-based methods for processing scATAC-seq data. These methods can fail to capture precise cell-type-specific regulatory signals, producing results that are difficult to interpret and lack portability, thereby compromising the reproducibility of research findings. To overcome these issues, we introduce CREscendo, a method that utilizes Tn5 cleavage frequencies and regulatory annotations to identify differential usage of candidate regulatory elements (CREs) across cell types. Our research advocates for moving away from traditional peak-based quantification in scATAC-seq toward a more robust framework that relies on a standardized reference of annotated CREs, enhancing both the accuracy and reproducibility of genomic studies.

Source: Cell Genomics

DOI: 10.1016/j.xgen.2025.100806

Author: Mengjie Chen

Institution: University of Chicago

Language: English

Topic: Single-cell and spatial transcriptomics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $8,900

Funders: National Institutes of Health, National Human Genome Research Institute, National Institute of General Medical Sciences