Duan Ran, Dang Dachang, Fan Shichen, Yao Shaowen, Zhang Shihua
Department of Communications Engineering, College of Information, Yunnan University, Kunming, 650091, China.
Key Laboratory of Information Fusion Technology of Ministry of Education, School of Automation, Northwestern Polytechnical University, Xi'an, 710072, China.
Commun Biol. 2025 Aug 27;8(1):1290. doi: 10.1038/s42003-025-07635-6.
Advanced high-throughput chromosome conformation capture techniques, like Hi-C, reveal genome organization into structural units like topologically associating domains (TADs), which are crucial in gene expression regulation. While accurately identifying TADs is vital, distinguishing different types of TAD boundaries and TAD categories remains a significant challenge in genomic research. We develop a Markov clustering-based tool, Mactop, to accurately identify TADs and provide biologically important classifications of TADs and their boundaries. Mactop distinguishes stable and dynamic boundaries based on biological significance. Mactop shows superior performance against multiple TAD-calling methods. More importantly, leveraging spatial interactions among TADs, Mactop uncovers TAD communities characterized by chromatin accessibility and enriched histone modifications. Mactop unveils the 'chromunity' within TADs in high-order interaction data, showing that interactions within TADs are diverse rather than uniform. In short, Mactop is a versatile, accurate, robust tool for deciphering chromatin domain, domain community, and chromunity for 3D genome maps.
先进的高通量染色体构象捕获技术,如Hi-C,揭示了基因组组织成拓扑相关结构域(TAD)等结构单元,这些结构单元在基因表达调控中至关重要。虽然准确识别TAD至关重要,但区分不同类型的TAD边界和TAD类别仍然是基因组研究中的一项重大挑战。我们开发了一种基于马尔可夫聚类的工具Mactop,以准确识别TAD,并提供TAD及其边界的生物学重要分类。Mactop根据生物学意义区分稳定和动态边界。Mactop在多种TAD调用方法中表现出卓越性能。更重要的是,利用TAD之间的空间相互作用,Mactop揭示了以染色质可及性和丰富的组蛋白修饰为特征的TAD群落。Mactop在高阶相互作用数据中揭示了TAD内的“染色质群落”,表明TAD内的相互作用是多样的而非均匀的。简而言之,Mactop是一种多功能、准确、强大的工具,用于解读三维基因组图谱中的染色质结构域、结构域群落和染色质群落。