# reDA: differential abundance testing on scATAC-seq data using random walk with restart

**Authors:** Zirui Chen, Jiao Hua, Lu Ba, Tianyun He, Boran Yang, Jing Qi, Shuilin Jin

PMC · DOI: 10.1093/bioinformatics/btaf459 · 2025-08-29

## TL;DR

reDA is a new method for analyzing scATAC-seq data that improves accuracy and efficiency in identifying cell states linked to diseases.

## Contribution

reDA introduces a cluster-free framework using random walk with restart for differential abundance testing in scATAC-seq data.

## Key findings

- reDA outperforms six baseline methods in accuracy and computational efficiency.
- reDA captures disease-specific molecular signatures from scATAC-seq data.
- reDA is compatible with existing scATAC-seq analysis workflows.

## Abstract

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. Through comprehensive experiments on simulated and real datasets, reDA outperforms six baseline methods, demonstrating superior accuracy, computational efficiency, and the ability to capture disease-specific molecular signatures.

The reDA along with detailed documentation is freely available at https://github.com/Jinsl-lab/reDA. It can be seamlessly integrated into existing scATAC-seq analysis workflows.

## Full-text entities

- **Genes:** KLF15 (KLF transcription factor 15) [NCBI Gene 28999] {aka KKLF}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], ZNF148 (zinc finger protein 148) [NCBI Gene 7707] {aka BERF-1, BFCOL1, GDACCF, HT-BETA, ZBP-89, ZFP148}, SP3 (Sp3 transcription factor) [NCBI Gene 6670] {aka SPR2}, EGR1 (early growth response 1) [NCBI Gene 1958] {aka AT225, G0S30, KROX-24, NGFI-A, TIS8, ZIF-268}, TFDP1 (transcription factor Dp-1) [NCBI Gene 7027] {aka DILC, DP1, DRTF1, Dp-1}, KLF16 (KLF transcription factor 16) [NCBI Gene 83855] {aka BTEB4, DRRF, NSLP2}
- **Diseases:** NAM (MESH:C535501), CRC (MESH:D015179), polyp (MESH:D011127), FAP (MESH:D011125), cancer (MESH:D009369)
- **Chemicals:** scATAC (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** 747 — Homo sapiens (Human), Glycine encephalopathy, Finite cell line (CVCL_CX01)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12553332/full.md

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Source: https://tomesphere.com/paper/PMC12553332