Enhancing Molecular Network-Based Cancer Driver Gene Prediction Using Machine Learning Approaches: Current Challenges and Opportunities

Abstract

Cancer is a complex disease driven by mutations in the genes that play critical roles in cellular processes. The identification of cancer driver genes is crucial for understanding tumorigenesis, developing targeted therapies and identifying rational drug targets. Experimental identification and validation of cancer driver genes are time-consuming and costly. Studies have demonstrated that interactions among genes are associated with similar phenotypes. Therefore, identifying cancer driver genes using molecular network-based approaches is necessary. Molecular network-based random walk-based approaches, which integrate mutation data with protein-protein interaction networks, have been widely employed in predicting cancer driver genes and demonstrated robust predictive potential. However, recent advancements in deep learning, particularly graph-based models, have provided novel opportunities for enhancing the prediction of cancer driver genes. This review aimed to comprehensively explore how machine learning methodologies, particularly network propagation, graph neural networks, autoencoders, graph embeddings, and attention mechanisms, improve the scalability and interpretability of molecular network-based cancer gene prediction.

Keywords: cancer driver gene; deep learning; graph neural network; machine learning; protein–protein interaction; random walk.