MCIBox: a toolkit for single-molecule multi-way chromatin interaction visualization and micro-domains identification

• Main Authors: Tian, Simon Zhongyuan, Li, Guoliang, Ning, Duo, Jing, Kai, Xu, Yewen, Yang, Yang, Fullwood, Melissa Jane, Yin, Pengfei, Huang, Guangyu, Plewczynski, Dariusz, Zhai, Jixian, Dai, Ziwei, Chen, Wei, Zheng, Meizhen
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Biological sciences; Single-Molecule; Micro-Domains
• Online Access: https://hdl.handle.net/10356/169673
• Institution: Nanyang Technological University

The emerging ligation-free three-dimensional (3D) genome mapping technologies can identify multiplex chromatin interactions with single-molecule precision. These technologies not only offer new insight into high-dimensional chromatin organization and gene regulation, but also introduce new challenges in data visualization and analysis. To overcome these challenges, we developed MCIBox, a toolkit for multi-way chromatin interaction (MCI) analysis, including a visualization tool and a platform for identifying micro-domains with clustered single-molecule chromatin complexes. MCIBox is based on various clustering algorithms integrated with dimensionality reduction methods that can display multiplex chromatin interactions at single-molecule level, allowing users to explore chromatin extrusion patterns and super-enhancers regulation modes in transcription, and to identify single-molecule chromatin complexes that are clustered into micro-domains. Furthermore, MCIBox incorporates a two-dimensional kernel density estimation algorithm to identify micro-domains boundaries automatically. These micro-domains were stratified with distinctive signatures of transcription activity and contained different cell-cycle-associated genes. Taken together, MCIBox represents an invaluable tool for the study of multiple chromatin interactions and inaugurates a previously unappreciated view of 3D genome structure.