Privacy-preserving multicenter differential protein abundance analysis with FedProt
Nature Computational Science, vol. 5, pp. 675–688
Abstract
Abstract 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 serious 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 E. coli experiments and one at three centers from human serum. Evaluations using these datasets confirm that FedProt achieves accuracy equivalent to the DEqMS method applied to pooled data, with completely negligible absolute differences no greater than 4 × 10−12. By contrast, −log10 P computed by the most accurate meta-analysis methods diverged from the centralized analysis results by up to 25–26.
Authors 31
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Yuliya P. Burankova corresponding
Universität Hamburg · Technical University of Munich
Affiliation as printed
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany. yuliya.burankova@tum.de
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany. yuliya.burankova@tum.de
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Technical University of Munich
Affiliation as printed
Bavarian Center for Biomolecular Mass Spectrometry, TUM School of Life Sciences, Technical University of Munich, Freising, Germany
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany
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Affiliation as printed
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany
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Affiliation as printed
Metabolomics and Proteomics Core, Helmholtz Center Munich, Munich, Germany
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Ludwig-Maximilians-Universität München
Affiliation as printed
Protein Analysis Unit, Biomedical Center, Faculty of Medicine, LMU Munich, Martinsried, Germany
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Max Planck Institute of Biochemistry
Affiliation as printed
Max Planck Institute of Biochemistry, Martinsried, Germany
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German Center for Neurodegenerative Diseases
Affiliation as printed
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
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Fraunhofer Institute for Cell Therapy and Immunology
Affiliation as printed
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany
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Coburg University of Applied Sciences · Fraunhofer Institute for Cell Therapy and Immunology
Affiliation as printed
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany
Institute for Bioanalysis, University of Applied Science Coburg, Coburg, Germany
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Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen
Affiliation as printed
Department of Nephrology, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
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Universitätsmedizin Greifswald · German Centre for Cardiovascular Research
Affiliation as printed
German Center for Cardiovascular Diseases (DZHK), Greifswald, Germany
University Medicine Greifswald, Greifswald, Germany
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Universität Hamburg · Technical University of Munich
Affiliation as printed
Data Science in Systems Biology, TUM School of Life Sciences, Technical University of Munich, Freising, Germany
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany
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Affiliation as printed
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany
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Leibniz Institute of Virology (LIV) · Universität Hamburg
Affiliation as printed
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany
Viral Systems Modeling, Leibniz Institute of Virology, Hamburg, Germany
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University of Southern Denmark · Friedrich-Alexander-Universität Erlangen-Nürnberg
Affiliation as printed
Department of Artificial Intelligence in Biomedical Engineering, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark
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University of Southern Denmark
Affiliation as printed
Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark
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Technical University of Munich
Affiliation as printed
Bavarian Center for Biomolecular Mass Spectrometry, TUM School of Life Sciences, Technical University of Munich, Freising, Germany
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Affiliation as printed
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany
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Affiliation as printed
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany
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University of Southern Denmark
Affiliation as printed
Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark
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University of Southern Denmark
Affiliation as printed
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
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Affiliation as printed
Metabolomics and Proteomics Core, Helmholtz Center Munich, Munich, Germany
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German Center for Neurodegenerative Diseases · TUM Klinikum · Munich Cluster for Systems Neurology · Technical University of Munich
Affiliation as printed
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Neuroproteomics, School of Medicine and Health, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
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Ludwig-Maximilians-Universität München
Affiliation as printed
Protein Analysis Unit, Biomedical Center, Faculty of Medicine, LMU Munich, Martinsried, Germany
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Max Planck Institute of Biochemistry
Affiliation as printed
Max Planck Institute of Biochemistry, Martinsried, Germany
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Technical University of Munich
Affiliation as printed
Bavarian Center for Biomolecular Mass Spectrometry, TUM School of Life Sciences, Technical University of Munich, Freising, Germany
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Technical University of Munich
Affiliation as printed
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany
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Universität Hamburg · University of Southern Denmark
Affiliation as printed
Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany
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Universität Hamburg · Technical University of Munich
Affiliation as printed
Data Science in Systems Biology, TUM School of Life Sciences, Technical University of Munich, Freising, Germany
Institute for Computational Systems Biology, University of Hamburg, Hamburg, Germany
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