Federated Survival Analysis in Healthcare: A Multi-Model Evaluation on Cross-Institutional Heterogeneous Breast Cancer Data

Survival analysis is central to clinical decision-making, yet reliable time-to-event models require large, diverse cohorts that are rarely available at a single institution, while privacy regulations restrict the centralization of patient data. Federated learning (FL) offers a privacy-preserving alternative by training shared models without exchanging raw data, but its effectiveness for survival modeling under realistic, heterogeneous conditions remains insufficiently understood. This paper presents a systematic, multi-model evaluation of federated survival analysis on a cross-institutional breast cancer cohort with naturally heterogeneous distributed clients. Three representative survival models, the Cox Proportional Hazards model, DeepSurv, and Random Survival Forest (RSF), are compared across centralized, local, and federated training, and three federated optimization strategies (FedAvg, FedProx, and FedAdam) are assessed for the gradient-based models. Results show that FL consistently outperforms local training and approaches, and occasionally exceeds, centralized performance, while RSF offers the best overall balance of discrimination, calibration, and robustness across heterogeneous clients. We further find that performance depends on the diversity of client distributions, and that FedAvg and FedProx are stronger and more stable than FedAdam. Based on these findings, we derive practical, decision-oriented guidelines mapping data, privacy, interpretability, and resource constraints to recommended model and training-paradigm choices for federated survival modeling in healthcare.

When Does Gene Regulatory Network Inference Break? A Controlled Diagnostic Study of Causal and Correlational Methods on Single-Cell Data

Despite theoretical advantages, causal methods for Gene Regulatory Network (GRN) inference from single-cell RNA-seq data consistently fail to match or outperform correlation-based baselines in many realistic benchmarks, a persistent puzzle which casts doubt on the value of causality for this task. We argue that existing benchmarks are insufficiently controlled to answer this question because they evaluate on real or semi-real data where multiple pathologies co-occur, confounding failure modes, and obscuring the specific conditions under which different inference methods excel or fail. To address this gap, we introduce a controlled diagnostic framework that isolates seven biologically motivated pathologies (dropout, latent confounders, cell-type mixing, feedback loops, network density, sample size, and pseudotime drift) and measure how six representative methods spanning three inference paradigms degrade as each pathology intensifies. Across 6,120 controlled experiments, we find that causal methods genuinely dominate in clean and structurally favorable regimes, but specific pathologies (notably dropout and latent confounders) selectively neutralize their advantages. We further introduce an error-type decomposition that reveals methods with similar aggregate accuracy commit qualitatively different errors. To probe whether single-pathology effects persist when multiple stressors co-occur, we perform an interaction sweep over the three most impactful pathologies and find that their joint effects are sub-additive, while also exposing density-conditional cross-overs invisible to single-dial analysis. Our findings offer a nuanced understanding of when and why different methods succeed or fail for GRN inference, providing actionable insights for method development and practical guidance for practitioners.