The article discusses the three-dimensional organization of genomes and the interpretation of chromatin interaction data. It highlights the use of chromosome conformation capture (3C) technologies, such as 3C, 4C, 5C, and Hi-C, to study the spatial arrangement of genomes at high resolution. These methods allow the identification of chromatin looping and long-range gene regulation, which are crucial for understanding how genes are accessed and expressed. The article reviews various statistical and computational approaches for analyzing chromatin interaction data, including restraint-based modeling and polymer physics-based methods. It also discusses the formation of topologically associating domains (TADs) and their role in gene regulation. The study emphasizes the importance of 3D modeling in understanding the complex structure of chromosomes and how it relates to gene expression and regulation. The article concludes with a discussion of future perspectives in the field, including the potential for new insights into the three-dimensional folding of chromosomes and its impact on genome biology.The article discusses the three-dimensional organization of genomes and the interpretation of chromatin interaction data. It highlights the use of chromosome conformation capture (3C) technologies, such as 3C, 4C, 5C, and Hi-C, to study the spatial arrangement of genomes at high resolution. These methods allow the identification of chromatin looping and long-range gene regulation, which are crucial for understanding how genes are accessed and expressed. The article reviews various statistical and computational approaches for analyzing chromatin interaction data, including restraint-based modeling and polymer physics-based methods. It also discusses the formation of topologically associating domains (TADs) and their role in gene regulation. The study emphasizes the importance of 3D modeling in understanding the complex structure of chromosomes and how it relates to gene expression and regulation. The article concludes with a discussion of future perspectives in the field, including the potential for new insights into the three-dimensional folding of chromosomes and its impact on genome biology.