论文标题

用于药物目标相互作用预测的细粒度选择性相似性集成

Fine-Grained Selective Similarity Integration for Drug-Target Interaction Prediction

论文作者

Liu, Bin, Wang, Jin, Sun, Kaiwei, Tsoumakas, Grigorios

论文摘要

药物目标相互作用(DTI)的发现是药物开发中的关键过程。计算方法是乏味且昂贵的湿lab实验的一种有前途且有效的替代方法,可预测来自众多候选者的新型DTI。最近,随着来自不同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种药物并靶向相似性来提高DTI预测的性能。相似性集成是一种有效且灵活的策略,可以在互补相似性视图中提取关键信息,为任何基于相似性的DTI预测模型提供压缩输入。但是,现有的相似性集成方法从全球角度过滤和融合了相似性,从而忽略了每种药物和目标的相似性观点的效用。在这项研究中,我们提出了一种称为FGS的细粒度选择性相似性整合方法,该方法采用了局部相互作用一致性的权重矩阵来捕获和利用在相似性选择和组合步骤中较细的粒度上相似性的重要性。我们在各种预测设置下评估了五个DTI预测数据集的FG。实验结果表明,我们的方法不仅优于相似的计算成本集成竞争对手,而且还可以通过与常规基本模型协作来实现比最先进的DTI预测方法更好的预测性能。此外,关于分析相似性权重的案例研究和新型预测的验证证实了FG的实际能力。

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.

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