Interpretable Graph Kolmogorov-Arnold Networks for Multi-Cancer Classification and Biomarker Identification using Multi-Omics Data

Abstract

The integration of heterogeneous multi-omics datasets at a systems level remains a central challenge for developing analytical and computational models in precision cancer diagnostics. This paper introduces Multi-Omics Graph Kolmogorov-Arnold Network (MOGKAN), a deep learning framework that utilizes messenger-RNA, micro-RNA sequences, and DNA methylation samples together with Protein-Protein Interaction (PPI) networks for cancer classification across 31 different cancer types. The proposed approach combines differential gene 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 and uses trainable univariate functions to enhance interpretability and feature analysis. MOGKAN achieves classification accuracy of 96.28 percent and exhibits low experimental variability in comparison to related deep learning-based models. The biomarkers identified by MOGKAN were validated as cancer-related markers through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. By integrating multi-omics data with graph-based deep learning, our proposed approach demonstrates robust predictive performance and interpretability with potential to enhance the translation of complex multi-omics data into clinically actionable cancer diagnostics.