Graph Kolmogorov-Arnold Networks for Multi-Cancer Classification and Biomarker Identification, An Interpretable Multi-Omics Approach

The integration of multi-omics data presents a major challenge in precision medicine, requiring advanced computational methods for accurate disease classification and biological interpretation. This study introduces the Multi-Omics Graph Kolmogorov-Arnold Network (MOGKAN), a deep learning model that integrates messenger RNA, micro RNA sequences, and DNA methylation data with Protein-Protein Interaction (PPI) networks for accurate and interpretable cancer classification across 31 cancer types. MOGKAN employs a hybrid approach combining differential expression with DESeq2, Linear Models for Microarray (LIMMA), and Least Absolute Shrinkage and Selection Operator (LASSO) regression to reduce multi-omics data dimensionality while preserving relevant biological features. The model architecture is based on the Kolmogorov-Arnold theorem principle, using trainable univariate functions to enhance interpretability and feature analysis. MOGKAN achieves classification accuracy of 96.28 percent and demonstrates low experimental variability with a standard deviation that is reduced by 1.58 to 7.30 percents compared to Convolutional Neural Networks (CNNs) and Graph Neural Networks (GNNs). The biomarkers identified by MOGKAN have been validated as cancer-related markers through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The proposed model presents an ability to uncover molecular oncogenesis mechanisms by detecting phosphoinositide-binding substances and regulating sphingolipid cellular processes. By integrating multi-omics data with graph-based deep learning, our proposed approach demonstrates superior predictive performance and interpretability that has the potential to enhance the translation of complex multi-omics data into clinically actionable cancer diagnostics.