HGP-Mamba: Integrating Histology and Generated Protein Features for Mamba-based Multimodal Survival Risk Prediction

Multimodal survival models can combine complementary prognostic information from whole-slide images and genomic profiles, but effective fusion remains challenging amid external cohort shift and computational complexity. To address these challenges, we propose MIST, multimodal survival prediction with genomic-guided histology attention. MIST represents genomic features as tokens and allows them to query compact foundation-model-derived histology context tokens before survival prediction. This design enriches molecular information with histology context rather than merging separately encoded modalities only at the final stage. Training combines discrete-time survival prediction with genomic feature masking, WSI dropout, and paired WSI-genomics contrastive alignment. Across four external evaluations in colon, renal, lung, and glioblastoma cohorts, MIST improves external C-index over standard fusion baselines in the primary comparisons. These results support genomic-guided histology attention as a compact and effective strategy for multimodal oncology outcome prediction. Our code is available at https://github.com/samiyavuuz/MIST .

We propose a novel multimodal deep learning framework for patient-level survival prediction, which integrates whole-slide histology features, RNA-seq expression profiles, and clinical variables. Our architecture combines an ABMIL module~\cite{ilse2018attention} for slide-level representation with feedforward encoders for RNA and clinical data. These embeddings are then integrated through low-rank bilinear cross-modal fusion~\cite{liu2018efficient} to model conditional interactions across modalities while controlling parameter growth. The model outputs continuous risk scores that are subsequently mapped to survival times using a nonparametric calibration procedure based on the Kaplan--Meier estimator~\cite{kaplan1958nonparametric}. By decomposing multimodal reasoning into independent pairwise interactions, the proposed fusion design promotes structural interpretability and parameter efficiency compared with full tensor and hierarchical fusion strategies. Experiments on the CHIMERA challenge dataset demonstrate improved predictive performance over concatenation-based baselines and competitive generalization on hidden evaluation cohorts. These results indicate that the proposed framework is a promising approach for multimodal survival prediction in HR-NMIBC. The implementation is publicly available at https://github.com/hassancpu/ChimeraChallenge2025_Task_3.

To enhance the precision of cancer prognosis, recent research has increasingly focused on multimodal survival methods by integrating genomic data and histology images. However, current approaches overlook the fact that the proteome serves as an intermediate layer bridging genomic alterations and histopathological features while providing complementary biological information essential for survival prediction. This biological reality exposes another architectural limitation: existing integrative analysis studies fuse these heterogeneous data sources in a flat manner that fails to capture their inherent biological hierarchy. To address these limitations, we propose HFGPI, a hierarchical fusion framework that models the biological progression from genes to proteins to histology images from a systems biology perspective. Specifically, we introduce Molecular Tokenizer, a molecular encoding strategy that integrates identity embeddings with expression profiles to construct biologically informed representations for genes and proteins. We then develop Gene-Regulated Protein Fusion (GRPF), which employs graph-aware cross-attention with structure-preserving alignment to explicitly model gene-protein regulatory relationships and generate gene-regulated protein representations. Additionally, we propose Protein-Guided Hypergraph Learning (PGHL), which establishes associations between proteins and image patches, leveraging hypergraph convolution to capture higher-order protein-morphology relationships. The final features are progressively fused across hierarchical layers to achieve precise survival outcome prediction. Extensive experiments on five benchmark datasets demonstrate the superiority of HFGPI over state-of-the-art methods.