A Novel Autoencoder-Based Feature Selection Method for Drug-Target Interaction Prediction with Human-Interpretable Feature Weights

Drug-target interaction prediction provides important information that could be exploited for drug discovery, drug design, and drug repurposing. Chemogenomic approaches for predicting drug-target interaction assume that similar receptors bind to similar ligands. Capturing this similarity in so-called “fingerprints” and combining the target and ligand fingerprints provide an efficient way to search for protein-ligand pairs that are more likely to interact. In this study, we constructed drug and target fingerprints by employing features extracted from the DrugBank. However, the number of extracted features is quite large, necessitating an effective feature selection mechanism since some features can be redundant or irrelevant to drug-target interaction prediction problems. Although such feature selection methods are readily available in the literature, usually they act as black boxes and do not provide any quantitative information about why a specific feature is preferred over another. To alleviate this lack of human interpretability, we proposed a novel feature selection method in which we used an autoencoder as a symmetric learning method and compared the proposed method to some popular feature selection algorithms, such as Kbest, Variance Threshold, and Decision Tree. The results of a detailed performance study, in which we trained six Multi-Layer Perceptron (MLP) Networks of different sizes and configurations for prediction, demonstrate that the proposed method yields superior results compared to the aforementioned methods