论文标题
通过相互作用恢复的加权最近邻居合奏的毒品目标相互作用预测
Drug-Target Interaction Prediction via an Ensemble of Weighted Nearest Neighbors with Interaction Recovery
论文作者
论文摘要
通过可靠的计算方法预测药物目标相互作用(DTI)是减轻药物发现过程的巨大成本和时间的有效方法。基于结构的药物相似性和基于序列的靶蛋白相似性是DTI预测的常用信息。在众多计算方法中,基于邻里的化学基因组学方法利用药物和靶向相似性直接进行预测是简单但有前途的预测。但是,需要重新训练现有的基于相似性的方法,以预测任何新药或靶标的相互作用,并且不能直接对新药,新靶标和新药物目标对进行预测。此外,当前DTI数据集中的大量缺失(未检测到的)相互作用阻碍了大多数DTI预测方法。为了解决这些问题,我们提出了一种新方法,称为具有相互作用恢复(WKNNIR)的加权k-neartient邻居。 WKNNIR不仅可以估计任何新药物和/或新目标的相互作用,而无需重新训练,而且还可以恢复缺失的相互作用(假否定性)。此外,WKNNIR利用当地的不平衡来促进更可靠的相似性对相互作用恢复和预测过程的影响。我们还提出了一系列采用各种抽样策略的合奏方法,可以与WKNNIR以及任何其他DTI预测方法相结合以提高性能。五个基准数据集的实验结果证明了我们方法在预测药物目标相互作用方面的有效性。最后,我们确认提出的方法发现原始基准数据集中未报告的可靠交互的实际预测能力。
Predicting drug-target interactions (DTI) via reliable computational methods is an effective and efficient way to mitigate the enormous costs and time of the drug discovery process. Structure-based drug similarities and sequence-based target protein similarities are the commonly used information for DTI prediction. Among numerous computational methods, neighborhood-based chemogenomic approaches that leverage drug and target similarities to perform predictions directly are simple but promising ones. However, existing similarity-based methods need to be re-trained to predict interactions for any new drugs or targets and cannot directly perform predictions for both new drugs, new targets, and new drug-target pairs. Furthermore, a large amount of missing (undetected) interactions in current DTI datasets hinders most DTI prediction methods. To address these issues, we propose a new method denoted as Weighted k-Nearest Neighbor with Interaction Recovery (WkNNIR). Not only can WkNNIR estimate interactions of any new drugs and/or new targets without any need of re-training, but it can also recover missing interactions (false negatives). In addition, WkNNIR exploits local imbalance to promote the influence of more reliable similarities on the interaction recovery and prediction processes. We also propose a series of ensemble methods that employ diverse sampling strategies and could be coupled with WkNNIR as well as any other DTI prediction method to improve performance. Experimental results over five benchmark datasets demonstrate the effectiveness of our approaches in predicting drug-target interactions. Lastly, we confirm the practical prediction ability of proposed methods to discover reliable interactions that were not reported in the original benchmark datasets.