The discovery of drug-target interactions (DTIs) is a pivotal process in pharmaceutical development. Computational approaches are a promising and efficient alternative to tedious and costly wet-lab experiments for predicting novel DTIs from numerous candidates. Recently, with the availability of abundant heterogeneous biological information from diverse data sources, computational methods have been able to leverage multiple drug and target similarities to boost the performance of DTI prediction. Similarity integration is an effective and flexible strategy to extract crucial information across complementary similarity views, providing a compressed input for any similarity-based DTI prediction model. However, existing similarity integration methods filter and fuse similarities from a global perspective, neglecting the utility of similarity views for each drug and target. In this study, we propose a Fine-Grained Selective similarity integration approach, called FGS, which employs a local interaction consistency-based weight matrix to capture and exploit the importance of similarities at a finer granularity in both similarity selection and combination steps. We evaluate FGS on five DTI prediction datasets under various prediction settings. Experimental results show that our method not only outperforms similarity integration competitors with comparable computational costs, but also achieves better prediction performance than state-of-the-art DTI prediction approaches by collaborating with conventional base models. Furthermore, case studies on the analysis of similarity weights and on the verification of novel predictions confirm the practical ability of FGS.
翻译:药物靶点相互作用预测的细粒度选择性相似度整合
药物靶点相互作用(DTIs)的发现是制药发展的关键过程。计算方法是预测来自众多候选项的新DTIs的一种有前途和高效的替代方法,以替代困难和昂贵的湿实验。最近,随着来自多种数据源的丰富异质生物学信息的可用性,计算方法已经能够利用多个药物和靶点相似性来提高DTI预测的性能。相似性整合是提取跨互补相似性视图的关键信息的有效和灵活策略,为任何基于相似性的DTI预测模型提供了压缩的输入。然而,现有的相似性整合方法从全局的角度过滤和合并相似性,忽略了每个药物和靶点的相似性视图的效用。在本研究中,我们提出了一种细粒度选择性相似度整合方法,称为FGS,它采用基于局部相互作用一致性的权重矩阵,以更精细的颗粒度捕获和利用相似性选择和组合步骤中相似性的重要性。我们在五个DTI预测数据集上使用FGS进行评估,在各种预测设置下进行评估。实验结果表明,我们的方法不仅在与可比较的计算成本的相似性整合竞争者相比的情况下表现优异,而且通过与传统基础模型的协作实现了比最先进的DTI预测方法更好的预测性能。此外,相似性权重分析和新预测的验证案例研究证实了FGS的实际能力。