SlideMamba: Entropy-Based Adaptive Fusion of GNN and Mamba for Enhanced Representation Learning in Digital Pathology

Advances in computational pathology increasingly rely on extracting meaningful representations from Whole Slide Images (WSIs) to support various clinical and biological tasks. In this study, we propose a generalizable deep learning framework that integrates the Mamba architecture with Graph Neural Networks (GNNs) for enhanced WSI analysis. Our method is designed to capture both local spatial relationships and long-range contextual dependencies, offering a flexible architecture for digital pathology analysis. Mamba modules excels in capturing long-range global dependencies, while GNNs emphasize fine-grained short-range spatial interactions. To effectively combine these complementary signals, we introduce an adaptive fusion strategy that uses an entropy-based confidence weighting mechanism. This approach dynamically balances contributions from both branches by assigning higher weight to the branch with more confident (lower-entropy) predictions, depending on the contextual importance of local versus global information for different downstream tasks. We demonstrate the utility of our approach on a representative task: predicting gene fusion and mutation status from WSIs. Our framework, SlideMamba, achieves an area under the precision recall curve (PRAUC) of 0.751 ± 0.05, outperforming MIL (0.491 ± 0.042), Trans-MIL (0.39 ± 0.017), Mamba-only (0.664 ± 0.063), GNN-only (0.748 ± 0.091), and a prior similar work GAT-Mamba (0.703 ± 0.075). SlideMamba also achieves competitive results across ROC AUC (0.738 ± 0.055), sensitivity (0.662 ± 0.083), and specificity (0.725 ± 0.094). These results highlight the strength of the integrated architecture, enhanced by the proposed entropy-based adaptive fusion strategy, and suggest promising potential for application of spatially-resolved predictive modeling tasks in computational pathology.