Wang Jianshi, Ohsawa Yukio
Department of Systems Innovation, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8656, Japan.
Sci Rep. 2025 May 18;15(1):17249. doi: 10.1038/s41598-025-01410-7.
Understanding chemical-protein interactions (CPIs) is crucial for drug discovery and biological research, yet their complexity often challenges traditional methods. We propose TCoCPIn, a novel framework integrating graph neural networks (GNN) with the comprehensive topological characteristics index (CTC), which combines multiple topological metrics to enhance predictive accuracy. TCoCPIn significantly outperforms traditional and embedding-based methods, achieving higher accuracy, precision, and recall in CPI prediction. A case study highlights its ability to predict potential interactions, such as between ibuprofen and TNF-alpha, demonstrating its utility in identifying novel therapeutic targets. These findings illustrate TCoCPIn's potential to uncover hidden associations and key nodes in CPI networks, providing new opportunities for drug discovery and disease mechanism exploration. Future work will focus on experimental validation and expanding the application of TCoCPIn to other biological systems.
理解化学-蛋白质相互作用(CPI)对于药物发现和生物学研究至关重要,然而其复杂性常常给传统方法带来挑战。我们提出了TCoCPIn,这是一个将图神经网络(GNN)与综合拓扑特征指数(CTC)相结合的新颖框架,该指数结合了多个拓扑指标以提高预测准确性。TCoCPIn显著优于传统方法和基于嵌入的方法,在CPI预测中实现了更高的准确率、精确率和召回率。一个案例研究突出了其预测潜在相互作用的能力,例如布洛芬与肿瘤坏死因子-α之间的相互作用,证明了其在识别新治疗靶点方面的实用性。这些发现说明了TCoCPIn在揭示CPI网络中隐藏关联和关键节点方面的潜力,为药物发现和疾病机制探索提供了新机会。未来的工作将集中在实验验证以及将TCoCPIn的应用扩展到其他生物系统。