Peak-agnostic high-resolution cis-regulatory circuitry mapping using single cell multiome data.

ABSTRACT: Single same cell RNAseq/ATACseq multiome data provide unparalleled potential to develop high resolution maps of the cell-type specific transcriptional regulatory circuitry underlying gene expression. We present CREMA, a framework that recovers the full cis-regulatory circuitry by modeling gene expression and chromatin activity in individual cells without peak-calling or cell type labeling constraints. We demonstrate that CREMA overcomes the limitations of existing methods that fail to identify about half of functional regulatory elements which are outside the called chromatin 'peaks'. These circuit sites outside called peaks are shown to be important cell type specific functional regulatory loci, sufficient to distinguish individual cell types. Analysis of mouse pituitary data identifies a

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC10810203 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature