Single-cell biclustering for cell-specific transcriptomic perturbation detection in AD progression

The pathogenesis of Alzheimer disease (AD) involves complex gene regulatory changes across different cell types. To help decipher this complexity, we introduce single-cell Bayesian biclustering (scBC), a framework for identifying cell-specific gene network biomarkers in scRNA and snRNA-seq data. Through biclustering, scBC enables the analysis of perturbations in functional gene modules at the single-cell level. Applying the scBC framework to AD snRNA-seq data reveals the perturbations within gene modules across distinct cell groups and sheds light on gene-cell correlations during AD progression. Notably, our method helps to overcome common challenges in single-cell data analysis, including batch effects and dropout events. Incorporating prior knowledge further enables the framework to yield more biologically interpretable results. Comparative analyses on simulated and real-world datasets demonstrate the precision and robustness of our approach compared to other state-of-the-art biclustering methods. scBC holds potential for unraveling the mechanisms underlying polygenic diseases characterized by intricate gene coexpression patterns.