Liu Qingyuan, Chen Zizhen, Wang Boyang, Pan Boyu, Zhang Zhuoyu, Shen Miaomiao, Zhao Weibo, Zhang Tingyu, Li Shao, Liu Liren
Department of Molecular Pharmacology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, 300060, China.
Institute for TCM-X, Department of Automation, Tsinghua University, Beijing, 100084, China.
Adv Sci (Weinh). 2025 Mar;12(11):e2409130. doi: 10.1002/advs.202409130. Epub 2025 Jan 28.
Efficient virtual screening methods can expedite drug discovery and facilitate the development of innovative therapeutics. This study presents a novel transfer learning model based on network target theory, integrating deep learning techniques with diverse biological molecular networks to predict drug-disease interactions. By incorporating network techniques that leverage vast existing knowledge, the approach enables the extraction of more precise and informative drug features, resulting in the identification of 88,161 drug-disease interactions involving 7,940 drugs and 2,986 diseases. Furthermore, this model effectively addresses the challenge of balancing large-scale positive and negative samples, leading to improved performance across various evaluation metrics such as an Area under curve (AUC) of 0.9298 and an F1 score of 0.6316. Moreover, the algorithm accurately predicts drug combinations and achieves an F1 score of 0.7746 after fine-tuning. Additionally, it identifies two previously unexplored synergistic drug combinations for distinct cancer types in disease-specific biological network environments. These findings are further validated through in vitro cytotoxicity assays, demonstrating the potential of the model to enhance drug development and identify effective treatment regimens for specific diseases.
高效的虚拟筛选方法可以加快药物发现,并促进创新疗法的开发。本研究提出了一种基于网络靶点理论的新型迁移学习模型,将深度学习技术与多种生物分子网络相结合,以预测药物-疾病相互作用。通过整合利用大量现有知识的网络技术,该方法能够提取更精确、更具信息性的药物特征,从而识别出涉及7940种药物和2986种疾病的88161种药物-疾病相互作用。此外,该模型有效地解决了大规模正样本和负样本平衡的挑战,在各种评估指标上都有了改进的表现,例如曲线下面积(AUC)为0.9298,F1分数为0.6316。此外,该算法能够准确预测药物组合,微调后F1分数达到0.7746。此外,它在疾病特异性生物网络环境中为不同癌症类型识别出两种以前未被探索的协同药物组合。这些发现通过体外细胞毒性试验得到了进一步验证,证明了该模型在增强药物开发和识别特定疾病有效治疗方案方面的潜力。