DNA双链断裂(DSBs)是最为有害的DNA损伤之一，如果未得到适当修复，则可能导致癌症。最近的染色体构象捕获技术，如Hi-C，已经使得能够确定3D染色质结构与DSBs之间的关系，但是从全局接触图来解释这些关系，尤其是它们对DSB形成的贡献，目前所知甚少。在此，我们提出了一种框架，该框架将图形神经网络(GNN)与先进的可解释技术GNNExplainer相结合，以揭示3D染色质结构与DSBs之间的关系。我们确定了一种名为DNA易损性相关染色质相互作用网络（Facin）的新染色质结构单元。 Facin是一种瓶颈式的结构，它有助于揭示一个通用形式，即一段DNA的易损性如何通过染色质相互作用受到整个基因组的影响。此外，我们证明，Facin中的瓶颈相互作用可以作为DSB形成的染色质结构决定因素。我们的研究提供了一种更系统化和精细化的视角，使人们更好地理解3D基因组背景下DSB形成机制的原理。© 2023. The Author(s)。

DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation.Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility-associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation.Our study provides a more systematic and refined view enabling a better understanding of the mechanisms of DSB formation under the context of the 3D genome.© 2023. The Author(s).