PACells identifies phenotype-associated cell states from single-cell chromatin accessibility profiles.

Identifying cell states that drive clinical phenotypes is crucial for dissecting regulatory landscapes, pathogenesis, and targeted therapies of disease in single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq). Here, we present PACells, a framework that links clinical phenotypes from bulk ATAC-seq data with individual cells from scATAC-seq data to identify critical cell states at single-cell resolution. PACells outperforms other methods in predicting cells and molecular signatures associated with disease and gene mutation. PACells discerns clinical cell states and regulatory elements relevant to Alzheimer disease (AD) and poor survival in glioblastoma. Further, PACells is extended to transcriptomics for melanoma datasets with immunotherapy outcomes.