Olga Zolotareva

Yuliya Burankova, Miriam Abele, Mohammad Bakhtiari et al.

Quantitative mass spectrometry has revolutionized proteomics by enabling simultaneous quantification of thousands of proteins. Pooling patient-derived data from multiple institutions enhances statistical power but raises significant privacy concerns. Here we introduce FedProt, the first privacy-preserving tool for collaborative differential protein abundance analysis of distributed data, which utilizes federated learning and additive secret sharing. In the absence of a multicenter patient-derived dataset for evaluation, we created two, one at five centers from LFQ E.coli experiments and one at three centers from TMT human serum. Evaluations using these datasets confirm that FedProt achieves accuracy equivalent to DEqMS applied to pooled data, with completely negligible absolute differences no greater than $\text{$4 \times 10^{-12}$}$. In contrast, -log10(p-values) computed by the most accurate meta-analysis methods diverged from the centralized analysis results by up to 25-27. FedProt is available as a web tool with detailed documentation as a FeatureCloud App.

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.

Julian Matschinske, Julian Späth, Reza Nasirigerdeh et al.

Machine Learning (ML) and Artificial Intelligence (AI) have shown promising results in many areas and are driven by the increasing amount of available data. However, this data is often distributed across different institutions and cannot be shared due to privacy concerns. Privacy-preserving methods, such as Federated Learning (FL), allow for training ML models without sharing sensitive data, but their implementation is time-consuming and requires advanced programming skills. Here, we present the FeatureCloud AI Store for FL as an all-in-one platform for biomedical research and other applications. It removes large parts of this complexity for developers and end-users by providing an extensible AI Store with a collection of ready-to-use apps. We show that the federated apps produce similar results to centralized ML, scale well for a typical number of collaborators and can be combined with Secure Multiparty Computation (SMPC), thereby making FL algorithms safely and easily applicable in biomedical and clinical environments.