DMAGT: Unveiling miRNA-Drug Associations by Integrating SMILES and RNA Sequence Structures through Graph Transformer Models

TL;DR

This paper introduces DMAGT, a graph transformer model that predicts drug-miRNA associations by integrating molecular and RNA sequence structures, significantly aiding drug development targeting miRNAs.

Contribution

The novel DMAGT model combines graph neural networks and transformer architecture to accurately predict drug-miRNA associations using structural embeddings.

Findings

Achieved up to 95.24% AUC on three datasets.

Validated 14 out of 20 predicted associations in practical tests.

Demonstrated superior performance over existing methods.

Abstract

MiRNAs, due to their role in gene regulation, have paved a new pathway for pharmacology, focusing on drug development that targets miRNAs. However, traditional wet lab experiments are limited by efficiency and cost constraints, making it difficult to extensively explore potential associations between developed drugs and target miRNAs. Therefore, we have designed a novel machine learning model based on a multi-layer transformer-based graph neural network, DMAGT, specifically for predicting associations between drugs and miRNAs. This model transforms drug-miRNA associations into graphs, employs Word2Vec for embedding features of drug molecular structures and miRNA base structures, and leverages a graph transformer model to learn from embedded features and relational structures, ultimately predicting associations between drugs and miRNAs. To evaluate DMAGT, we tested its performance on three datasets composed of drug-miRNA associations: ncDR, RNAInter, and SM2miR, achieving up to AUC of $95.24\pm0.05$. DMAGT demonstrated superior performance in comparative experiments tackling similar challenges. To validate its practical efficacy, we specifically focused on two drugs, namely 5-Fluorouracil and Oxaliplatin. Of the 20 potential drug-miRNA associations identified as the most likely, 14 were successfully validated. The above experiments demonstrate that DMAGT has an excellent performance and stability in predicting drug-miRNA associations, providing a new shortcut for miRNA drug development.