Federated deep learning enables cancer subtyping by proteomics.

Artificial intelligence applications in biomedicine face major challenges from data privacy requirements. To address this issue for clinically annotated tissue proteomic data, we developed a Federated Deep Learning (FDL) approach (ProCanFDL), training local models on simulated sites containing data from a pan-cancer cohort (n=1,260) and 29 cohorts held behind private firewalls (n=6,265), representing 19,930 replicate data-independent acquisition mass spectrometry (DIA-MS) runs. Local parameter updates were aggregated to build the global model, achieving a 43% performance gain on the hold-out test set (n=625) in 14 cancer subtyping tasks compared to local models, and matching centralized model performance. The approach's generalizability was demonstrated by retraining the global model with data from two external DIA-MS cohorts (n=55) and eight acquired by tandem mass tag (TMT) proteomics (n=832). ProCanFDL presents a solution for internationally collaborative machine learning initiatives using proteomic data, e.g., for discovering predictive biomarkers or treatment targets, while maintaining data privacy.