Abstract

The prediction of drug-target interaction (DTI) is a key step in drug repositioning. In recent years, many studies have tried to use matrix factorization to predict DTI, but they only use known DTIs and ignore the features of drug and target expression profiles, resulting in limited prediction performance. In this study, we propose a new DTI prediction model named AdvB-DTI. Within this model, the features of drug and target expression profiles are associated with Adversarial Bayesian Personalized Ranking through matrix factorization. Firstly, according to the known drug-target relationships, a set of ternary partial order relationships is generated. Next, these partial order relationships are used to train the latent factor matrix of drugs and targets using the Adversarial Bayesian Personalized Ranking method, and the matrix factorization is improved by the features of drug and target expression profiles. Finally, the scores of drug-target pairs are achieved by the inner product of latent factors, and the DTI prediction is performed based on the score ranking. The proposed model effectively takes advantage of the idea of learning to rank to overcome the problem of data sparsity, and perturbation factors are introduced to make the model more robust. Experimental results show that our model could achieve a better DTI prediction performance.

Highlights

  • Drug repositioning is to discover new indications for existing drugs, which means that drug development based on approved drugs does not need to consider the safety and effectiveness of the original drug, effectively reducing the time of drug development process and cost

  • Experimental results show that our method is significantly better than the traditional drug-target interaction (DTI) prediction methods, such as Deep Neural Network (DNN) [8, 29], Generalized Matrix Factorization (GMF) [30], and other state-of-the-art learning to rank (LTR) methods, like Neural Matrix Factorization (NeuMF) [30] and Adversarial Matrix Factorization (AMF) [28]

  • We tuned the parameters of each method so that they could achieve the best performance in comparison

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Summary

Introduction

Drug repositioning is to discover new indications for existing drugs, which means that drug development based on approved drugs does not need to consider the safety and effectiveness of the original drug, effectively reducing the time of drug development process and cost. Existing machine learning-based methods often use the features of drugs and targets for prediction [5, 6]. They treat the prediction problem as a binary classification problem [7]. Mei et al improved the original DTI prediction framework by integrate neighbor-based interaction-profile inferring (NII) into the existing BLM method [12]. Laarhoven et al proposed a Gaussian interaction profiling (GIP) kernel to represent the interactions between drugs and targets [14] and integrated the weighted nearest neighbor method into it to predict DTIs [15]. Some studies constructed a heterogeneous network which integrates diverse drug-

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