TIER-MoE: Trust-Informed Expert Routing via Conditional Modality Risk for Multimodal Fusion in Biomedical Classification

Multimodal learning is a robust approach to improve predictive performance in applications such as medical prognosis. However, the clinical applicability of models that use multimodal learning is hampered by their poor performance under noisy or uninformative data streams. Present fusion approaches often lack robust mechanisms for the dynamic assessment of data quality and for the provision of a trustable confidence score on the final prediction. This dissuades their deployment in safety-critical settings. To address these limitations, we introduce Adaptive Confidence-weighted Expansion (ACE), a novel framework to enhance the trustworthiness of multimodal fusion models. ACE first enhances the multimodal space by generating new, complementary modalities from intra-modality correlations. It then employs a dual-level confidence mechanism that (1) adaptively reweighs all modalities by their reliability before fusion and (2) estimates a global trust score over the fused, final decision. To evaluate ACE, we used four challenging multi-omics datasets (BRCA, KIPAN, LGG, and ROSMAP). ACE significantly outperforms existing state-of-the-art algorithms in both classification performance and confidence calibration. Our framework provides a more stable and robust data fusion method that facilitates the use of multimodal learning in addressing high-stakes problems.

Multimodal clinical prediction faces three challenges: multiple foundation models (FMs) with complementary strengths per modality, pervasive missing modalities at training and test time, and sample-specific variation in modality contributions. We introduce MedMIX, a multimodal framework that combines intra-modality expert fusion, learned inter-modality fusion, and training-only large--small model collaboration for robust medical prediction under incomplete modalities. Within each modality, MedMIX aggregates complementary embeddings from multiple small expert models; across modalities, it performs learned fusion over available modalities; and during training, it leverages large teacher models to improve deployed representations without additional inference cost. Across three heterogeneous benchmarks (OpenI, MIMIC-IV-MM, and MMIST-ccRCC), MedMIX achieves consistently strong performance while remaining robust under controlled missing-modality perturbations, and further demonstrates sustained robustness under cross-cohort shift on MIMIC-III. These results highlight MedMIX as a practical framework that unifies within-modality expert collaboration, sample-specific cross-modality fusion, and efficient large--small model collaboration while remaining robust to incomplete modalities.

AI models for multimodal medical imaging must balance modality-specific specialization with cross-modal shared representations, a trade-off that pure Mixture-of-Experts (MoE) architectures currently fail to satisfy. Expert-based routing improves in-domain learning but may sacrifice cross-modal signals, which appear particularly important for rare (low-prevalence) pathologies in our experiments. To resolve this, we introduce Generalist-Specialist-MoE (GS-MoE), a two-branch (MoE) architecture that couples a cross-modal generalist model with distinct modality-specific specialists (experts) via domain-constrained feature fusion. On RadImageNet (1.35M images, 165 pathologies, three modalities), GS-MoE recovers detection of six low-prevalence pathologies on which every baseline scores F1 $=$ 0, with per-class gains up to +0.60 F1. It attains this while even slightly exceeding dense and specialist-only MoE aggregate baselines (MCC 0.770), while using ${\sim}53\%$ fewer active parameters at inference than the strongest investigated dense model.