Paper ID: 2407.15220

Privacy-Preserving Multi-Center Differential Protein Abundance Analysis with FedProt

Yuliya Burankova, Miriam Abele, Mohammad Bakhtiari, Christine von Törne, Teresa Barth, Lisa Schweizer, Pieter Giesbertz, Johannes R. Schmidt, Stefan Kalkhof, Janina Müller-Deile, Peter A van Veelen, Yassene Mohammed, Elke Hammer, Lis Arend, Klaudia Adamowicz, Tanja Laske, Anne Hartebrodt, Tobias Frisch, Chen Meng, Julian Matschinske, Julian Späth, Richard Röttger, Veit Schwämmle, Stefanie M. Hauck, Stefan Lichtenthaler, Axel Imhof, Matthias Mann, Christina Ludwig, Bernhard Kuster, Jan Baumbach, Olga Zolotareva

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.

Submitted: Jul 21, 2024