Epiregulon: Single-cell transcription factor activity inference to predict drug response and drivers of cell states.

ABSTRACT: Transcription factors (TFs) and transcriptional coregulators are emerging therapeutic targets. Gene regulatory networks (GRNs) can evaluate pharmacological agents and identify drivers of disease, but methods that rely solely on gene expression often neglect post-transcriptional modulation of TFs. We present Epiregulon, a method that constructs GRNs from single-cell ATAC-seq and RNA-seq data for accurate prediction of TF activity. This is achieved by considering the co-occurrence of TF expression and chromatin accessibility at TF binding sites in each cell. ChIP-seq data allows motif-agonistic activity inference of transcriptional coregulators or TF harboring neomorphic mutations. Epiregulon accurately predicted the effects of AR inhibition across different drug modalities including an AR a

SUBMITTER: Wlodarczyk T 

PROVIDER: S-EPMC12318008 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature