Scooby: Modeling multi-modal genomic profiles from DNA sequence at single-cell resolution.

ABSTRACT: Understanding how regulatory DNA elements shape gene expression across individual cells is a fundamental challenge in genomics. Joint RNA-seq and epigenomic profiling provides opportunities to build unifying models of gene regulation capturing sequence determinants across steps of gene expression. However, current models, developed primarily for bulk omics data, fail to capture the cellular heterogeneity and dynamic processes revealed by single-cell multi-modal technologies. Here, we introduce scooby, the first framework to model scRNA-seq coverage and scATAC-seq insertion profiles along the genome from sequence at single-cell resolution. For this, we leverage the pre-trained multi-omics profile predictor Borzoi as a foundation model, equip it with a cell-specific decoder, and fine-tune it

SUBMITTER: Hingerl JC 

PROVIDER: S-EPMC11429888 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature