I-Modern: Integrated multi-omics network model identifies potential therapeutic targets in glioma by deep learning with interpretability

Abstract

Effective and precise classification of glioma patients for their disease risks is critical to improving early diagnosis and patient survival. In the recent past, a significant amount of multi-omics data derived from cancer patients has emerged. However, a robust framework for integrating multi-omics data types to efficiently and precisely subgroup glioma patients and predict survival prognosis is still lacking. In addition, effective therapeutic targets for treating glioma patients with poor prognoses are in dire need. To begin to resolve this difficulty, we developed i-Modern, an integrated Multi-omics deep learning network method, and optimized a sophisticated computational model in gliomas that can accurately stratify patients based on their prognosis. We built a survival-associated predictive framework integrating transcription profile, miRNA expression, somatic mutations, copy number variation (CNV), DNA methylation, and protein expression. This framework achieved promising performance in distinguishing high-risk glioma patients from those with good prognoses. Furthermore, we constructed multiple fully connected neural networks that are trained on prioritized multi-omics signatures or even only potential single-omics signatures, based on our customized scoring system. Together, the landmark multi-omics signatures we identified may serve as potential therapeutic targets in gliomas.