DropHiChew 与 loop velocity:基于液滴的高效染色质构象捕获及 DNA 运动分析
Exploring DNA movement through the application of droplet-based high-efficiency chromatin conformation capture (DropHiChew) and loop velocity
研究提出 DropHiChew,一种基于液滴的高效染色质构象捕获方法,借助 10× Genomics 单细胞系统实现,作者称其使用门槛低、成本可控。研究同时开发 loop velocity 算法,通过量化染色质移动来估计细胞发育的速度和方向,在每细胞 50k contacts 的浅测序深度下仍能判断 DNA 运动轨迹和细胞状态。方法在 HEK293T、精子发生和胚胎发育等体系中做了验证。作者认为,DropHiChew 与 loop velocity 结合可为染色质捕获研究提供多种应用,并为疾病建模、细胞分化和发育生物学提供观察基因组组织的动态视角。
来源:Nucleic Acids Research · doi.org
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.