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. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=187 HEIGHT=200 SRC="FIGDIR/small/499656v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1705cc8org.highwire.dtl.DTLVardef@1db89adorg.highwire.dtl.DTLVardef@2be8e4org.highwire.dtl.DTLVardef@c6f1a6_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefGong et al. provide a toolkit MINE to explore the relationship between spatial density of regulatory chromatin interactions, gene expression and chromatin structure change. HighlightsO_LIMINE toolkit was provided to detect more regulatory chromatin interactions (RCI), count the spatial density of regulatory chromatin interactions and visualize the density of chromatin interactions with transcription factors in three-dimension. C_LIO_LIChromatin regions were divided into developed active hub, developing active hub, developed repressive hub, and developing repressive hub according to the density of active or repressive regulatory chromatin interactions. C_LIO_LIThe change of chromatin structure before and after liquid-liquid phase separation is quantitively described by using the MINE toolkit. C_LI