Exploring DNA movement through the application of droplet-based high-efficiency chromatin conformation capture (DropHiChew) and loop velocity

Abstract

This study presents a novel approach to understanding DNA movement dynamics. Chromatin conformation plays a crucial role in controlling gene expression and cellular processes, with abnormalities linked to diseases like cancer and genetic disorders. ​Current single-cell chromatin conformation methods face limitations in cost-effectiveness, accessibility, and capturing dynamic genome architecture.​​ Therefore, we develop ​DropHiChew, a droplet-based, highly efficient chromatin conformation capture method employing 10× Genomics single-cell systems for user-friendly, cost-effective implementation. Combined with our ​loop velocity algorithm—which estimates the speed and direction of cell development by quantifying chromatin movement—this approach accurately gauges the trajectory of DNA motion and cellular states even at shallow sequencing depth (50k contacts per cell). Validation demonstrates its applicability across biological systems, including HEK293T, spermiogenesis, and embryonic development. The integration of DropHiChew and loop velocity offers potential for diverse applications in chromatin capture studies. This paradigm provides a dynamic perspective on genome organization for disease modeling, cellular differentiation, and developmental biology.