论文标题

DTI-SNNFRA:共享最近的邻居和模糊的近似值的药物目标相互作用预测

DTI-SNNFRA: Drug-Target interaction prediction by shared nearest neighbors and fuzzy-rough approximation

论文作者

Islam, Sk Mazharul, Hossain, Sk Md Mosaddek, Ray, Sumanta

论文摘要

对可再利用药物的核内预测是一种有效的药物发现策略,可从头开始补充尼沃药物发现。减少的开发时间,降低的成本和缺乏严重的副作用是使用药物重新定位的重要优势。最新和最先进的人工智能(AI)方法在吞吐量和准确性方面促进了药物重新利用。但是,随着药物的数量越来越多,靶标及其大规模相互作用会产生不平衡的数据,这些数据可能直接不适合分类模型。在这里,我们提出了DTI-SNNFRA,这是一个基于共享最近的邻居(SNN)和模糊rough近似(FRA)的预测药物目标相互作用(DTI)的框架。它使用抽样技术共同减少涵盖可用药物,目标和数百万相互作用的巨大搜索空间。 DTI-SNNFRA分为两个阶段:首先,它使用SNN,然后使用分区聚类来对搜索空间进行采样。接下来,它计算了从药物和第一阶段获得的药物之间的所有可能相互作用对的负样品的不足采样的模糊距离近似程度和适当的度阈值选择。最后,使用正面和选定的负样本进行分类。我们使用AUC(ROC曲线下的区域),几何平均值和F1评分评估了DTI-SNNFRA的功效。该模型表现出色,ROC-AUC的高预测评分为0.95。预测的药物目标相互作用通过现有的药物目标数据库(连接图(CMAP))验证。

In-silico prediction of repurposable drugs is an effective drug discovery strategy that supplements de-nevo drug discovery from scratch. Reduced development time, less cost and absence of severe side effects are significant advantages of using drug repositioning. Most recent and most advanced artificial intelligence (AI) approaches have boosted drug repurposing in terms of throughput and accuracy enormously. However, with the growing number of drugs, targets and their massive interactions produce imbalanced data which may not be suitable as input to the classification model directly. Here, we have proposed DTI-SNNFRA, a framework for predicting drug-target interaction (DTI), based on shared nearest neighbour (SNN) and fuzzy-rough approximation (FRA). It uses sampling techniques to collectively reduce the vast search space covering the available drugs, targets and millions of interactions between them. DTI-SNNFRA operates in two stages: first, it uses SNN followed by a partitioning clustering for sampling the search space. Next, it computes the degree of fuzzy-rough approximations and proper degree threshold selection for the negative samples' undersampling from all possible interaction pairs between drugs and targets obtained in the first stage. Finally, classification is performed using the positive and selected negative samples. We have evaluated the efficacy of DTI-SNNFRA using AUC (Area under ROC Curve), Geometric Mean, and F1 Score. The model performs exceptionally well with a high prediction score of 0.95 for ROC-AUC. The predicted drug-target interactions are validated through an existing drug-target database (Connectivity Map (Cmap)).

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