Comparative analysis of mRNA and protein degradation in prostate tissues indicates high stability of proteins

Wenguang Shao, Tiannan Guo (), Nora C. Toussaint, Peng Xue, Ulrich Wagner, Li Li, Konstantina Charmpi, Yi Zhu, Jianmin Wu, Marija Buljan, Rui Sun, Dorothea Rutishauser, Thomas Hermanns, Christian Daniel Fankhauser, Cedric Poyet, Jelena Ljubicic, Niels Rupp, Jan H. Rüschoff, Qing Zhong, Andreas Beyer, Jiafu Ji, Ben C. Collins, Yansheng Liu, Gunnar Rätsch, Peter J. Wild () and Ruedi Aebersold ()
Additional contact information
Wenguang Shao: Institute of Molecular Systems Biology, ETH Zurich
Tiannan Guo: Institute of Molecular Systems Biology, ETH Zurich
Nora C. Toussaint: NEXUS Personalized Health Technologies, ETH Zurich
Peng Xue: Institute of Molecular Systems Biology, ETH Zurich
Ulrich Wagner: University Hospital Zurich
Li Li: University of Cologne
Konstantina Charmpi: University of Cologne
Yi Zhu: Institute of Molecular Systems Biology, ETH Zurich
Jianmin Wu: Peking University Cancer Hospital & Institute
Marija Buljan: Institute of Molecular Systems Biology, ETH Zurich
Rui Sun: Westlake University
Dorothea Rutishauser: University Hospital Zurich
Thomas Hermanns: University of Zurich, University Hospital Zurich
Christian Daniel Fankhauser: University of Zurich, University Hospital Zurich
Cedric Poyet: University of Zurich, University Hospital Zurich
Jelena Ljubicic: University Hospital Zurich
Niels Rupp: University Hospital Zurich
Jan H. Rüschoff: University Hospital Zurich
Qing Zhong: University Hospital Zurich
Andreas Beyer: University of Cologne
Jiafu Ji: Peking University Cancer Hospital & Institute
Ben C. Collins: Institute of Molecular Systems Biology, ETH Zurich
Yansheng Liu: Yale University School of Medicine
Gunnar Rätsch: SIB Swiss Institute of Bioinformatics
Peter J. Wild: University Hospital Zurich
Ruedi Aebersold: Institute of Molecular Systems Biology, ETH Zurich

Nature Communications, 2019, vol. 10, issue 1, 1-8

Abstract: Abstract Deterioration of biomolecules in clinical tissues is an inevitable pre-analytical process, which affects molecular measurements and thus potentially confounds conclusions from cohort analyses. Here, we investigate the degradation of mRNA and protein in 68 pairs of adjacent prostate tissue samples using RNA-Seq and SWATH mass spectrometry, respectively. To objectively quantify the extent of protein degradation, we develop a numerical score, the Proteome Integrity Number (PIN), that faithfully measures the degree of protein degradation. Our results indicate that protein degradation only affects 5.9% of the samples tested and shows negligible correlation with mRNA degradation in the adjacent samples. These findings are confirmed by independent analyses on additional clinical sample cohorts and across different mass spectrometric methods. Overall, the data show that the majority of samples tested are not compromised by protein degradation, and establish the PIN score as a generic and accurate indicator of sample quality for proteomic analyses.

Date: 2019
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DOI: 10.1038/s41467-019-10513-5

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