Deep Neural Network Integrated into Network-Based Stratification (D3NS): A Method to Uncover Cancer Subtypes from Somatic Mutations

Simple Summary Cancer develops through a complex process involving genetic changes that can lead to uncontrolled cell growth and tumor formation. This research focuses on developing an advanced approach to classify tumors into meaningful subgroups based on somatic mutations. Using machine learning techniques, specifically a deep neural network, and integrating genetic data with known gene interaction networks, we propose a framework for tumor stratification, called D3NS (deep neural network integrated into network-based stratification). This framework identifies patient subtypes predictive for survival and significantly associated with several clinical outcomes (tumor stage, grade and treatment response). We applied D3NS to real-world data from the Cancer Genome Atlas for bladder, ovarian, and kidney cancers. The results demonstrate the potential of this approach to improve cancer stratification, positioning it as a useful base model for cancer research and a promising tool in clinical settings.Abstract (1) Background: The identification of tumor subtypes is fundamental in precision medicine for accurate diagnoses and personalized therapies. Cancer development is often driven by the accumulation of somatic mutations that can cause alterations in tissue functions and morphologies. In this work, a method based on a deep neural network integrated into a network-based stratification framework (D3NS) is proposed to stratify tumors according to somatic mutations. (2) Methods: This approach leverages the power of deep neural networks to detect hidden information in the data by combining the knowledge contained in a network of gene interactions, as typical of network-based stratification methods. D3NS was applied using real-world data from The Cancer Genome Atlas for bladder, ovarian, and kidney cancers. (3) Results: This technique allows for the identification of tumor subtypes characterized by different survival rates and significant associations with several clinical outcomes (tumor stage, grade or response to therapy). (4) Conclusion: D3NS can provide a base model in cancer research and could be considered as a useful tool for tumor stratification, offering potential support in clinical settings.