Explainable AI for Precision Oncology: A Task-Specific Hierarchical Ensemble of Omics Classifiers

Abstract

Despite continued advances in oncology, cancer remains a leading cause of global mortality, highlighting the need for diagnostic and prognostic tools that are both accurate and interpretable. Unimodal approaches often fail to capture the biological and clinical complexity of tumors. In this study, we present a suite of task-specific AI models that leverage CT imaging, multi-omics profiles, and structured clinical data to address distinct challenges in segmentation, classification, and prognosis. We developed three independent models across large public datasets. Task 1 applied a 3D U-Net to segment pancreatic tumors from CT scans, achieving a Dice Similarity Coefficient (DSC) of 0.7062. Task 2 employed a hierarchical ensemble of omics-based classifiers to distinguish tumor from normal tissue and classify six major cancer types with 98.67% accuracy. Task 3 benchmarked classical machine learning models on clinical data for prognosis prediction across three cancers (LIHC, KIRC, STAD), achieving strong performance (e.g., C-index of 0.820 in KIRC, AUC of 0.978 in LIHC). Across all tasks, explainable AI methods such as SHAP and attention-based visualization enabled transparent interpretation of model outputs. These results demonstrate the value of tailored, modality aware models and underscore the clinical potential of applying such tailored AI systems for precision oncology.