Adaptive Confidence-weighted Expansion for Trustworthy Multi-Omics Multimodal Fusion
Authors: Mohammad Raahemi, Ali Sekhavati, Alireza Maleki, Hamid Nasiri
Organizations: Faculty of Engineering, University of Ottawa, Ottawa ON K1N 1A2, Canada · RIV Lab, Department of Computer Engineering, Bu-Ali Sina University, Hamedan, Iran · School of Computing and Communications, Lancaster University, Lancaster, UK
Abstract
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.
The promise of multimodal fusion lies in combining complementary sources of evidence, yet more evidence does not always yield a better prediction. Recent multimodal models have advanced fusion through richer cross-modal interaction and sample-adaptive fusion. However, the influence assigned to a modality during fusion does not reveal whether that source is unreliable, redundant, or poorly matched to a specialized expert. To address this limitation, we introduce TIER-MoE, a risk-guided subspace mixture-of-experts model that defines sample-specific modality reliability as the prediction loss its unimodal predictor is expected to incur. This risk is learned from out-of-fold predictions generated by models that were not trained on the corresponding sample. TIER-MoE combines the estimated risk with expert-specific subspace compatibility for sparse modality-expert routing, while an always-active shared path preserves multimodal complementarity. We evaluate TIER-MoE on four public multimodal biomedical datasets spanning Alzheimer's disease status, skin-lesion malignancy, and retinal classification. Results demonstrate its superiority over state-of-the-art methods in predictive performance and probability calibration, with consistent improvements in Macro-F1 and Brier score and strong zero-shot generalization to an external cohort.
Multimodal fusion requires integrating information from multiple sources that may conflict depending on context. Existing fusion approaches typically rely on static assumptions about source reliability, limiting their ability to resolve conflicts when a modality becomes unreliable due to situational factors such as sensor degradation or class-specific corruption. We introduce C2MF, a context-specfic credibility-aware multimodal fusion framework that models per-instance source reliability using a Conditional Probabilistic Circuit (CPC). We formalize instance-level reliability through Context-Specific Information Credibility (CSIC), a KL-divergence-based measure computed exactly from the CPC. CSIC generalizes conventional static credibility estimates as a special case, enabling principled and adaptive reliability assessment. To evaluate robustness under cross-modal conflicts, we propose the Conflict benchmark, in which class-specific corruptions deliberately induce discrepancies between different modalities. Experimental results show that C2MF improves predictive accuracy by up to 29% over static-reliability baselines in high-noise settings, while preserving the interpretability advantages of probabilistic circuit-based fusion.
Multimodal fusion learning (MFL) has shown great potential in the medical domain, where we are faced with disparate data modalities such as imaging, clinical records, and omics. However, existing MFL strategies face several major challenges. First, they struggle to capture complex cross-modal interactions effectively, which in turn limits performance improvements. Second, they incur high computational costs, restricting their applicability in resource-constrained healthcare AI applications. Finally, they are often designed and evaluated for narrow, fixed modality configurations (e.g., imaging-only, or specific pairs such as image and omics), which limits evidence of their adaptability and generalizability to broader collections of heterogeneous medical modalities. To address these challenges, we propose a novel MFL framework - Cascaded Unified Representation Learning for Efficient Fusion Network (CURE) - a lightweight and scalable framework that progressively integrates various modalities through a novel efficient Hybrid Geometry Aware Fusion layer (HyFuse), where each HyFuse layer is sequentially learned for each modality, making the framework adaptable and generalizable. Within HyFuse, an efficient residual convolution module captures rich multi-scale features to ensure cost-effective learning, while a hybrid-space aware attention mixer learns coarse-to-fine structural cues to better preserve cross-modal relationships. Complementary learnable late-fusion and shared information refinement modules are then employed to learn robust modality-order-invariant shared representations, which in turn yields consistent performance improvements. Extensive evaluations on 16 public datasets show that CURE outperforms leading multimodal fusion methods, boosting performance by up to 3.97% and lowering computational costs by up to 87.8%, ensuring more effective and reliable predictions.