Niklas Probul

Supratim Das, Mahdie Rafie, Paula Kammer et al.

Background: Patient-reported survey data are used to train prognostic models aimed at improving healthcare. However, such data are typically available multi-centric and, for privacy reasons, cannot easily be centralized in one data repository. Models trained locally are less accurate, robust, and generalizable. We present and apply privacy-preserving federated machine learning techniques for prognostic model building, where local survey data never leaves the legally safe harbors of the medical centers. Methods: We used centralized, local, and federated learning techniques on two healthcare datasets (GLA:D data from the five health regions of Denmark and international SHARE data of 27 countries) to predict two different health outcomes. We compared linear regression, random forest regression, and random forest classification models trained on local data with those trained on the entire data in a centralized and in a federated fashion. Results: In GLA:D data, federated linear regression (R2 0.34, RMSE 18.2) and federated random forest regression (R2 0.34, RMSE 18.3) models outperform their local counterparts (i.e., R2 0.32, RMSE 18.6, R2 0.30, RMSE 18.8) with statistical significance. We also found that centralized models (R2 0.34, RMSE 18.2, R2 0.32, RMSE 18.5, respectively) did not perform significantly better than the federated models. In SHARE, the federated model (AC 0.78, AUROC: 0.71) and centralized model (AC 0.84, AUROC: 0.66) perform significantly better than the local models (AC: 0.74, AUROC: 0.69). Conclusion: Federated learning enables the training of prognostic models from multi-center surveys without compromising privacy and with only minimal or no compromise regarding model performance.

Michael Hartung, Andreas Maier, Yuliya Burankova et al.

Unsupervised patient stratification is essential for disease subtype discovery, yet, despite growing evidence of molecular heterogeneity of non-oncological diseases, popular methods are benchmarked primarily using cancers with mutually exclusive molecular subtypes well-differentiated by numerous biomarkers. Evaluating 22 unsupervised methods, including clustering and biclustering, using simulated and real transcriptomics data revealed their inefficiency in scenarios with non-mutually exclusive subtypes or subtypes discriminated only by few biomarkers. To address these limitations and advance precision medicine, we developed UnPaSt, a novel biclustering algorithm for unsupervised patient stratification based on differentially expressed biclusters. UnPaSt outperformed widely used patient stratification approaches in the de novo identification of known subtypes of breast cancer and asthma. In addition, it detected many biologically insightful patterns across bulk transcriptomics, proteomics, single-cell, spatial transcriptomics, and multi-omics datasets, enabling a more nuanced and interpretable view of high-throughput data heterogeneity than traditionally used methods.

Yuliya Burankova, Julian Klemm, Jens J. G. Lohmann et al.

Batch effects in omics data obscure true biological signals and constitute a major challenge for privacy-preserving analyses of distributed patient data. Existing batch effect correction methods either require data centralization, which may easily conflict with privacy requirements, or lack support for missing values and automated workflows. To bridge this gap, we developed fedRBE, a federated implementation of limma's removeBatchEffect method. We implemented it as an app for the FeatureCloud platform. Unlike its existing analogs, fedRBE effectively handles data with missing values and offers an automated, user-friendly online user interface (https://featurecloud.ai/app/fedrbe). Leveraging secure multi-party computation provides enhanced security guarantees over classical federated learning approaches. We evaluated our fedRBE algorithm on simulated and real omics data, achieving performance comparable to the centralized method with negligible differences (no greater than 3.6E-13). By enabling collaborative correction without data sharing, fedRBE facilitates large-scale omics studies where batch effect correction is crucial.