Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, SK, Canada.
School of Mathematics and Statistics, Huazhong Normal University, Wuhan, China.
PLoS One. 2022 Jul 21;17(7):e0270852. doi: 10.1371/journal.pone.0270852. eCollection 2022.
Computational drug repositioning aims to identify potential applications of existing drugs for the treatment of diseases for which they were not designed. This approach can considerably accelerate the traditional drug discovery process by decreasing the required time and costs of drug development. Tensor decomposition enables us to integrate multiple drug- and disease-related data to boost the performance of prediction. In this study, a nonnegative tensor decomposition for drug repositioning, NTD-DR, is proposed. In order to capture the hidden information in drug-target, drug-disease, and target-disease networks, NTD-DR uses these pairwise associations to construct a three-dimensional tensor representing drug-target-disease triplet associations and integrates them with similarity information of drugs, targets, and disease to make a prediction. We compare NTD-DR with recent state-of-the-art methods in terms of the area under the receiver operating characteristic (ROC) curve (AUC) and the area under the precision and recall curve (AUPR) and find that our method outperforms competing methods. Moreover, case studies with five diseases also confirm the reliability of predictions made by NTD-DR. Our proposed method identifies more known associations among the top 50 predictions than other methods. In addition, novel associations identified by NTD-DR are validated by literature analyses.
计算药物重定位旨在为未设计用于治疗疾病的现有药物寻找潜在应用。这种方法可以通过减少药物开发所需的时间和成本,大大加快传统的药物发现过程。张量分解使我们能够整合多种与药物和疾病相关的数据,以提高预测性能。在这项研究中,提出了一种用于药物重定位的非负张量分解方法,即 NTD-DR。为了捕捉药物-靶标、药物-疾病和靶标-疾病网络中的隐藏信息,NTD-DR 使用这些两两关联来构建一个三维张量,代表药物-靶标-疾病三联体关联,并将其与药物、靶标和疾病的相似性信息集成,以进行预测。我们在接收者操作特征 (ROC) 曲线下面积 (AUC) 和精度-召回率曲线下面积 (AUPR) 方面将 NTD-DR 与最近的最先进方法进行了比较,发现我们的方法优于竞争方法。此外,对五种疾病的案例研究也证实了 NTD-DR 预测的可靠性。与其他方法相比,我们的方法在前 50 个预测中识别出了更多的已知关联。此外,NTD-DR 识别出的新关联通过文献分析得到了验证。