Drug-Target Interaction Prediction: End-to-End Deep Learning Approach

Authors

Nelson R. C. Monteiro
Bernardete Ribeiro
Joel P. Arrais

Abstract

The discovery of potential Drug-Target Interactions (DTIs) is a determining step in the drug discovery and repositioning process, as the effectiveness of the currently available antibiotic treatment is declining. Although putting efforts on the traditional in vivo or in vitro methods, pharmaceutical financial investment has been reduced over the years. Therefore, establishing effective computational methods is decisive to find new leads in a reasonable amount of time. Successful approaches have been presented to solve this problem but seldom protein sequences and structured data are used together. In this paper, we present a deep learning architecture model, which exploits the particular ability of Convolutional Neural Networks (CNNs) to obtain 1D representations from protein sequences (amino acid sequence) and compounds SMILES (Simplified Molecular Input Line Entry System) strings. These representations can be interpreted as features that express local dependencies or patterns that can then be used in a Fully Connected Neural Network (FCNN), acting as a binary classifier. The results achieved demonstrate that using CNNs to obtain representations of the data, instead of the traditional descriptors, lead to improved performance. The proposed end-to-end deep learning method outperformed traditional machine learning approaches in the correct classification of both positive and negative interactions.

Keywords

Proteins;Drugs;Chemicals;Machine learning;Diffusion tensor imaging;Predictive models;Bioinformatics;Drug Repositioning;Drug-Target Interaction;Deep Learning;Convolutional Neural Network;Fully Connected Neural Network;Protein Sequence;SMILES;Drug

Subject

Computational Drug Discovery

Related Project

D4 - Deep Drug Discovery and Deployment (PI: Bernardete Ribeiro; co-PI: Joel P. Arrais)