February 23, 2023

Platform for Proteomics

Platform, SMOC

Short Summary

The PHRT ETH Clinical Proteotype Analysis Center (CPAC), together with the PHRT ETH Clinical Metabolome Analysis Center (CMAC) and the PHRT EPFL Clinical Genome Analysis Center (CGAC), constitutes a central pillar of the PHRT/SPHN multi-omics strategy for precision medicine. Since their establishment, these centers have operated as an integrated infrastructure- the Swiss-Multi-Omics Center (SMOC)- enabling coordinated, high-quality multi-omics data generation from clinical biospecimens.

Goals

CPAC’s core objective is to deliver high-quality, standardized proteomics profiling of clinical cohorts and to integrate the generated data with complementary omics layers. This allows systems-level characterization of disease and supports the translation of molecular insights into clinically actionable information.

Significance

The Swiss Multi-Omics Center represents a critical infrastructure for advancing precision medicine in Switzerland. Within SMOC, CPAC provides the functional molecular layer required to interpret disease biology and contributes to the development of data-driven, mechanism-informed healthcare strategies.

Background

Proteomics provides a direct functional readout of biological processes and is essential for linking molecular variation to phenotype. CPAC provides the expertise, technologies, and standardized workflows necessary to enable high-quality poteomics within integrated multi-omics studies.

Publications

Choi M, Carver J, Chiva C, Tzouros M, Huang T, Tsai T-H, et al. quant: A community resource of quantitative mass spectrometry–based proteomics datasets. Nat Methods. 2020;17: 981–984. doi:10.1038/s41592-020-0955-0
Čuklina J, Lee CH, Williams EG, Sajic T, Collins BC, Rodríguez Martínez M, et al. Diagnostics and correction of batch effects in large-scale proteomic studies: a tutorial. Mol Syst Biol. 2021;17: e10240. doi:10.15252/msb.202110240
Forny P, Bonilla X, Lamparter D, Shao W, Plessl T, Frei C, et al. Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency. Nature Metabolism. 2023;5: 80–95. doi:10.1038/s42255-022-00720-8
Fossati A, Li C, Uliana F, Wendt F, Frommelt F, Sykacek P, et al. PCprophet: a framework for protein complex prediction and differential analysis using proteomic data. Nat Methods. 2021;18: 520–527. doi:10.1038/s41592-021-01107-5
Frey K, Goetze S, Rohrer L, von Eckardstein A, Wollscheid B. Decoding Functional High-Density Lipoprotein Particle Surfaceome Interactions. Int J Mol Sci. 2022;23. doi:10.3390/ijms23169506
Frey K, Rohrer L, Potapenko A, Goetze S, von Eckardstein A, Wollscheid B. Mapping the dynamic cell surface interactome of high-density lipoprotein reveals Aminopeptidase N as modulator of its endothelial uptake. bioRxiv. 2023. p. 2023.01.03.522574. doi:10.1101/2023.01.03.522574
Goetze S, Frey K, Rohrer L, Radosavljevic S, Krützfeldt J, Landmesser U, et al. Reproducible Determination of High-Density Lipoprotein Proteotypes. J Proteome Res. 2021;20: 4974–4984. doi:10.1021/acs.jproteome.1c00429
Goetze S, Schüffler P, Athanasiou A, Koetemann A, Poyet C, Fankhauser CD, et al. Use of MS-GUIDE for identification of protein biomarkers for risk stratification of patients with prostate cancer. Clin Proteomics. 2022;19: 9. doi:10.1186/s12014-022-09349-x
Lee S, Weiss T, Bühler M, Mena J, Lottenbach Z, Wegmann R, et al. Targeting tumour-intrinsic neural vulnerabilities of glioblastoma. bioRxiv. 2022. p. 2022.10.07.511321. doi:10.1101/2022.10.07.511321
Nina Zila, Ossia M. Eichhoff, Irene Steiner, Thomas Mohr, Andrea Bileck, Phil F. Cheng, Alexander Leitner, Ludovic Gillet, Tatjana Sajic, Sandra Goetze, Betty Friedrich, Patricia Bortel, Johanna Strobl, René Reitermaier, Sabrina A. Hogan, Julia M. Martínez-Gómez, Ramon Staeger, Felix Tuchmann, Sophie Peters, Georg Stary, Mario Kuttke, Adelheid Elbe-Buerger, Christoph Hoeller, Rainer Kunstfeld, Wolfgang Weninger, Bernd Wollscheid, Reinhard Dummer, Lars E. French, Christopher Gerner, Ruedi Aebersold, Mitchell P. Levesque, Verena Paulitschke; Proteomic profiling of advanced melanoma patients to predict therapeutic response to anti-PD-1 therapy. Clin Cancer Res 2023; https://doi.org/10.1158/1078-0432.CCR-23-0562
Uliana F, Vizovisek M, Acquasaliente L, Ciuffa R, Fossati A, Frommelt F, Goetze S, et al. Mapping specificity, cleavage entropy, allosteric changes and substrates in blood proteases by a high-throughput protease screen. Nat Commun. 2021;12(1), 1693. https://doi.org/10.1038/s41467-021-21754-8
Wendt F, Milani ES, Wollscheid B. Elucidation of host-virus surfaceome interactions using spatial proteotyping. Adv Virus Res. 2021;109: 105–134. doi:10.1016/bs.aivir.2021.03.002
Xuan Y, Bateman NW, Gallien S, Goetze S, Zhou Y, Navarro P, et al. Standardization and harmonization of distributed multi-center proteotype analysis supporting precision medicine studies. Nat Commun. 2020;11: 5248. doi:10.1038/s41467-020-18904-9