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Nat Commun. 2019 Jun 7;10(1):2524. doi: 10.1038/s41467-019-10513-5.

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

Author information

1
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, 8093, Switzerland.
2
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, 8093, Switzerland. guotiannan@westlake.edu.cn.
3
School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou, 310024, Zhejiang Province, China. guotiannan@westlake.edu.cn.
4
Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, 310024, Zhejiang Province, China. guotiannan@westlake.edu.cn.
5
NEXUS Personalized Health Technologies, ETH Zurich, Zurich, 8093, Switzerland.
6
SIB Swiss Institute of Bioinformatics, Zurich, 8093, Switzerland.
7
Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
8
Institute of Surgical Pathology, University Hospital Zurich, Zurich, 8091, Switzerland.
9
CECAD, University of Cologne, Cologne, 50931, Germany.
10
School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou, 310024, Zhejiang Province, China.
11
Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou, 310024, Zhejiang Province, China.
12
Key laboratory of Carcinogenesis and Translational Research, Center for Cancer Bioinformatics, Peking University Cancer Hospital & Institute, Beijing, 100091, China.
13
Department of Urology, University of Zurich, University Hospital Zurich, Zurich, 8091, Switzerland.
14
Cancer Data Science Group, Children's Medical Research Institute, University of Sydney, Sydney, 2050, NSW, Australia.
15
Key laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, 100091, China.
16
Department of Pharmacology, Cancer Biology Institute, Yale University School of Medicine, West Haven, CT, 06516, USA.
17
Department of Computer Science, ETH Zurich, Zurich, 8093, Switzerland.
18
Institute of Surgical Pathology, University Hospital Zurich, Zurich, 8091, Switzerland. peter.wild@kgu.de.
19
Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt am Main, 60590, Germany. peter.wild@kgu.de.
20
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, 8093, Switzerland. aebersold@imsb.biol.ethz.ch.
21
Faculty of Science, University of Zurich, Zurich, 8057, Switzerland. aebersold@imsb.biol.ethz.ch.

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.

PMID:
31175306
DOI:
10.1038/s41467-019-10513-5
[Indexed for MEDLINE]

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