Single-cell 3D genome technologies provide unprecedented views of chromatin architecture, but the extreme sparsity and noise of contact maps limit robust detection of chromatin loops at the individual cell level. Here we present CellLoop, a computational framework for identifying chromatin loops from single-cell contact data by integrating intra-cellular and neighboring inter-cellular contacts through a density-based voting strategy. Applied to Dip-C data from the mouse brain, CellLoop achieves improved loop detection consistent with spatial distances and compartmentalization signals, revealing single cell-specific chromatin loops associated with transcriptional regulation and cell identity. In HiRES embryogenesis data, CellLoop enables finer cell subtype delineation by reducing confounding cell cycle effects. Integration with GAGE-seq and MERFISH data redefines spatial domain functions through chromatin loop dynamics. Together, CellLoop provides a scalable and accurate approach for characterizing chromatin loop variability at single-cell resolution and highlights the utility of 3D genome features in interpreting transcriptional and spatial heterogeneity.
Publication: NATURE COMMUNICATIONS
http://dx.doi.org/10.1038/s41467-026-71406-y
Author: Ye, Yusen, Xidian Univ, Sch Comp Sci & Technol, Xian, Shaanxi, Peoples R China
Email：ysye@xidian.edu.cn
Wang, Yiheng, Xidian Univ, Sch Comp Sci & Technol, Xian, Shaanxi, Peoples R China
Liu, Shiji, Xidian Univ, Sch Comp Sci & Technol, Xian, Shaanxi, Peoples R China
Hu, Yuxuan, Xidian Univ, Sch Comp Sci & Technol, Xian, Shaanxi, Peoples R China
Yu, Liang, Xidian Univ, Sch Comp Sci & Technol, Xian, Shaanxi, Peoples R ChinaWang, Weibing, Xidian Univ, Sch Comp Sci & Technol, Xian, Shaanxi, Peoples R China
Gao, Lin(corresponding author), Xidian Univ, Sch Comp Sci & Technol, Xian, Shaanxi, Peoples R ChinaEmail：lgao@mail.xidian.edu.cn
Zhang, Shihua, Chinese Acad Sci, Acad Math & Syst Sci, CEMS, RCSDS,NCMIS, Beijing, Peoples R China, Univ Chinese Acad Sci, Sch Math Sci, Beijing, Peoples R China, Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov,Chinese Acad S, Hangzhou, Peoples R China
Chen, Hebing, Acad Mil Med Sci, Beijing, Peoples R China
Email：chenhb@bmi.ac.cn
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