MoESurv: A Zero-Sample and Transferable Survival Prediction Framework for Rare Cancers Using Mixture of Experts.

MOTIVATION: Accurate survival prediction is crucial for personalized cancer treatment but remains challenging for rare cancers due to limited data. Most deep learning models require large training datasets, which are unavailable for rare cancer types, creating a significant clini-cal bottleneck. RESULTS: We propose MoESurv, a zero-sample survival prediction framework that leverages a mix-ture-of-experts architecture to extract generalizable prognostic patterns from pan-cancer data. The model integrates shared experts, cancer-specific experts, and routing experts within an autoencoder to disentangle common and type-specific survival features. Evaluated on seven rare TCGA cancer types, MoESurv achieved state-of-the-art performance, improving the average C-index by 4 percentage points over the best baseline. Further-more, external validation across diverse populations and independent cohorts-including a Chinese glioma cohort (CGGA mRNAseq_693, C-index=0.7433), a rare GBM IDH-mutant subtype (C-index=0.8064), and the pan-cancer PCAWG cohort (C-index=0.7090)-demonstrated that MoESurv possesses the most robust predictive per-formance, highlighting its generalizability. MoESurv also effectively stratified high- and low-risk patient groups and identified potential survival-associated genes, demonstrating both clinical utility and biological interpretability. AVAILABILITY: The code is freely available at  https://github.com/HuaYC666/MoESurv and https://zenodo.org/records/20785500. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.