Engineering FAIR Privacy-preserving Applications that Learn Histories of Disease

The rapid adoption of data-driven methods in biomedicine has intensified concerns over privacy, governance, and regulation, limiting raw data sharing and hindering the assembly of representative cohorts for clinically relevant AI. This landscape necessitates practical, efficient privacy solutions, as cryptographic defenses often impose heavy overhead and differential privacy can degrade performance, leading to sub-optimal outcomes in real-world settings. Here, we present a lightweight federated learning method, INFL, based on Implicit Neural Representations that addresses these challenges. Our approach integrates plug-and-play, coordinate-conditioned modules into client models, embeds a secret key directly into the architecture, and supports seamless aggregation across heterogeneous sites. Across diverse biomedical omics tasks, including cohort-scale classification in bulk proteomics, regression for perturbation prediction in single-cell transcriptomics, and clustering in spatial transcriptomics and multi-omics with both public and private data, we demonstrate that INFL achieves strong, controllable privacy while maintaining utility, preserving the performance necessary for downstream scientific and clinical applications.

Medical artificial intelligence (AI) models are often shared without their training data, assuming this protects the patients who contributed them. However, a model can reveal whether a patient's records were used in training, a privacy breach known as a membership inference attack. This risk is usually reported as a cohort average, which can appear negligible while individual patients are almost certainly exposed. Identifying potentially vulnerable records before developing a production model could make privacy assessment more practical. We measured each patient's vulnerability to membership inference attack, across 7,789 models trained on six clinical datasets in four modalities, including two adapted pretrained medical models. Training choices changed how many patients had high attack scores, but the patients who ranked highest by risk largely stayed the same across the configurations we tested. Stronger weight decay reduced the exposed cohort up to threefold, yet largely the same patients remained most at risk across training recipes, architectures and initializations, including foundation models. Therefore, we developed a lightweight screening tool that uses four small models to identify patients with high risk of exposure before production-model training. We also assessed if flagged patients could be protected without removing their data. Privacy screening should become incorporated into data preparation for clinical AI.

Federated learning (FL) has become a foundational paradigm for multi-institutional medical AI, allowing hospitals and research centers to jointly train diagnostic models without exchanging patient records. This privacy promise, however, is increasingly contested: a malicious or honest-but-curious server can launch model inversion attacks (MIAs) that reconstruct private patient images directly from shared model updates, and recent scalable, closed-form attacks penetrate even secure aggregation at clinically realistic batch sizes. Existing defenses face an unsatisfactory dilemma. Gradient-perturbation methods such as differential privacy and pruning trade away the diagnostic accuracy on which clinical reliability depends, while cryptographic protocols add system complexity yet still leave updates exposed to these scalable attacks. We propose Aegis, a principled client-side defense that breaks this dilemma without perturbing patient data or modifying the FL protocol. Our key insight is that the success of every known MIA is fundamentally bounded by the local batch size relative to the model's leakage capacity; once this limit is exceeded, distinct samples collide and reconstructions collapse into indistinguishable mixtures. Aegis turns this universal bottleneck into a defense: each client superimposes onto its real update a masking gradient computed on locally synthesized, task-relevant data, deliberately pushing the effective batch beyond the attack's recovery capacity. We complement the design with theoretical convergence guarantees under standard convex assumptions and evaluate Aegis on MNIST, CIFAR-10, and three MedMNIST modalities (chest X-ray, abdominal CT, colon pathology). Aegis neutralizes three state-of-the-art MIAs while preserving model utility and incurring only modest overhead, offering a practical privacy primitive for medical FL.