Drug-target interaction prediction via multiple classification strategies

Abstract

Background: Computational prediction of the interaction between drugs and protein targets is very important for the new drug discovery, as the experimental determination of drug-target interaction (DTI) is expensive and time-consuming. However, different protein targets are with very different numbers of interactions. Specifically, most interactions focus on only a few targets. As a result, targets with larger numbers of interactions could own enough positive samples for predicting their interactions but the positive samples for targets with smaller numbers of interactions could be not enough. Only using a classification strategy may not be able to deal with the above two cases at the same time. To overcome the above problem, in this paper, a drug-target interaction prediction method based on multiple classification strategies (MCSDTI) is proposed. In MCSDTI, targets are firstly divided into two parts according to the number of interactions of the targets, where one part contains targets with smaller numbers of interactions (TWSNI) and another part contains targets with larger numbers of interactions (TWLNI). And then different classification strategies are respectively designed for TWSNI and TWLNI to predict the interaction. Furthermore, TWSNI and TWLNI are evaluated independently, which can overcome the problem that result could be mainly determined by targets with large numbers of interactions when all targets are evaluated together.

Results: We propose a new drug-target interaction (MCSDTI) prediction method, which uses multiple classification strategies. MCSDTI is tested on five DTI datasets, such as nuclear receptors (NR), ion channels (IC), G protein coupled receptors (GPCR), enzymes (E), and drug bank (DB). Experiments show that the AUCs of our method are respectively 3.31%, 1.27%, 2.02%, 2.02% and 1.04% higher than that of the second best methods on NR, IC, GPCR and E for TWLNI; And AUCs of our method are respectively 1.00%, 3.20% and 2.70% higher than the second best methods on NR, IC, and E for TWSNI.

Conclusion: MCSDTI is a competitive method compared to the previous methods for all target parts on most datasets, which administrates that different classification strategies for different target parts is an effective way to improve the effectiveness of DTI prediction.

Keywords: Drug–target interaction; Multiple classification strategies; Within-class imbalance.

Fig. 1

The distribution of interactions on five datasets, where Feature vector extraction

Fig. 2

The flowchart of MCSDTI

Fig. 3

An example used to show the negative impact of samples of the neighbors

Fig. 4

Histogram of AUCs for TWLNI, where $\tau$ used in Algorithm.1 are respectively set to 1, 3 and 5

Fig. 5

Histogram of AUCs for TWSNI, where $\tau$ used in Algorithm.1 are respectively set to 1, 3 and 5