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MVSGDR:用于药物重新定位的多视图堆叠图卷积网络

MVSGDR: multi-view stacked graph convolutional network for drug repositioning.

作者信息

Gu Guosheng, Wu Haowei, Han Haojie, Lin Zhiyi, Sun Yuping, Xie Guobo, Su Qing, Liu Zhenguo

机构信息

School of Computer Science and Technology, Guangdong University of Technology, Waihuan West Road 100, Guangzhou, 510006 Guangdong, China.

Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan Second Road 58, Guangzhou, 510080 Guangdong, China.

出版信息

Brief Bioinform. 2025 Aug 31;26(5). doi: 10.1093/bib/bbaf396.

Abstract

Drug repositioning (DR) presents a cost-effective strategy for drug development by identifying novel therapeutic applications for existing drugs. Current computational approaches remain constrained by their inability to synergize localized substructure patterns with global network semantics, leading to overreliance on data augmentation to mitigate latent drug-disease association (DDA) information gaps. To address these limitations, we present multi-view stacked graph convolutional network (MVSGDR), a novel DR framework featuring three technical innovations: (i) multi-view stacked module that enables depth-wise feature enhancement through hierarchical aggregation of multi-hop neighborhood interactions across distinct graph convolutional layers; (ii) bi-level subgraph transformer module that decomposes DDAs into METIS (a graph partitioning tool) informative subgraphs for breadth-wise analysis of external and internal subgraph drug-disease relationships; and (iii) negative sampling balancing strategy that mitigates sample imbalance through negative sample synthesis. Extensive 10-fold cross-validation experiments across four benchmark datasets confirm MVSGDR's superior performance, demonstrating its statistically significant improvements over existing methods. Moreover, case studies further validate MVSGDR's potential utility through identification of previously unreported DDAs with supporting literature evidence.

摘要

药物重新定位(DR)通过识别现有药物的新治疗应用,为药物开发提供了一种具有成本效益的策略。当前的计算方法仍然受到限制,因为它们无法将局部子结构模式与全局网络语义协同起来,导致过度依赖数据增强来减轻潜在的药物-疾病关联(DDA)信息差距。为了解决这些限制,我们提出了多视图堆叠图卷积网络(MVSGDR),这是一种新颖的DR框架,具有三项技术创新:(i)多视图堆叠模块,通过跨不同图卷积层的多跳邻域交互的层次聚合实现深度特征增强;(ii)双层子图变压器模块,将DDA分解为METIS(一种图划分工具)信息子图,用于对外部和内部子图药物-疾病关系进行广度分析;(iii)负采样平衡策略,通过负样本合成减轻样本不平衡。在四个基准数据集上进行的广泛的10折交叉验证实验证实了MVSGDR的卓越性能,表明其相对于现有方法有统计学上的显著改进。此外,案例研究通过识别具有支持文献证据的先前未报告的DDA,进一步验证了MVSGDR的潜在效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b26b/12403086/62861814fcec/bbaf396f1.jpg

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