MINE is a method for detecting spatial density of regulatory chromatin interactions based on a MultI-modal NEtwork

Abstract

Chromatin interactions play essential roles in chromatin conformation and gene expression. However, few tools exist to analyze the spatial density of regulatory chromatin interactions. Here, we present the MultI-modal NEtwork (MINE) toolkit, including MINE-Loop, MINE-Density, and MINE-Viewer. MINE-Loop network modeling integrates Hi-C, ATAC-seq, and histone ChIP-seq data to enhance the detection of regulatory chromatin interactions (RCIs, i.e., chromatin interactions that are anchoring regulatory elements to chromatin); MINE-Density quantifies the spatial density of regulatory chromatin interactions identified by MINE-Loop within different chromatin conformations; and MINE-Viewer facilitates 3D visualization of the density of chromatin interactions and participating regulatory factors, such as transcription factors. We applied MINE to investigate the relationship between the spatial density of regulatory chromatin interactions (SD-RCI) and chromatin volume change in HeLa cells before and after liquid-liquid phase separation. Changes in SD-RCI before and after treating the HeLa cells with 1,6-hexanediol showed that the change in chromatin volume was related to the degree of activation or repression of genes in chromatin interactions. The MINE toolkit provides a new method for quantitative study of chromatin conformation.