Taylor & Francis Group
Browse
ieru_a_1483340_sm4035.pdf (504.76 kB)

Detecting post-translational modification signatures as potential biomarkers in clinical mass spectrometry

Download (504.76 kB)
journal contribution
posted on 2018-07-03, 07:27 authored by Ruzanna Mnatsakanyan, Gerta Shema, Mark Basik, Gerald Batist, Christoph H. Borchers, Albert Sickmann, René P. Zahedi

Introduction: Numerous diseases are caused by changes in post-translational modifications (PTMs). Therefore, the number of clinical proteomics studies that include the analysis of PTMs is increasing. Combining complementary information—for example changes in protein abundance, PTM levels, with the genome and transcriptome (proteogenomics)—holds great promise for discovering important drivers and markers of disease, as variations in copy number, expression levels, or mutations without spatial/functional/isoform information is often insufficient or even misleading.

Areas covered: We discuss general considerations, requirements, pitfalls, and future perspectives in applying PTM-centric proteomics to clinical samples. This includes samples obtained from a human subject, for instance (i) bodily fluids such as plasma, urine, or cerebrospinal fluid, (ii) primary cells such as reproductive cells, blood cells, and (iii) tissue samples/biopsies.

Expert commentary: PTM-centric discovery proteomics can substantially contribute to the understanding of disease mechanisms by identifying signatures with potential diagnostic or even therapeutic relevance but may require coordinated efforts of interdisciplinary and eventually multi-national consortia, such as initiated in the cancer moonshot program. Additionally, robust and standardized mass spectrometry (MS) assays—particularly targeted MS, MALDI imaging, and immuno-MALDI—may be transferred to the clinic to improve patient stratification for precision medicine, and guide therapies.

Funding

The authors R. Mnatsakanyan, G.Shema, A. Sickmann were supported by the Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen, the Senatsverwaltung für Wirtschaft, Technologie und Forschung des Landes Berlin, and the Bundesministerium für Bildung und Forschung. C.H. Borchers and R.P.Zahedi are grateful to Genome Canada and Genome British Columbia for financial support (project codes 204PRO for operations and 214PRO for technology development). CHB is also grateful for support from the Leading Edge Endowment Fund (University of Victoria) and for support from the Segal McGill Chair in Molecular Oncology at McGill University (Montreal, Quebec, Canada). C.H.Borchers, A.Spatz, M.Basik and G.Batist are grateful for support from the Warren Y. Soper Charitable Trust and the Alvin Segal Family Foundation to the Jewish General Hospital (Montreal, Quebec, Canada). A.Spatz, M.Basik and G.Batist are also grateful for support from Genome Canada's Business-Led Networks of Centres of Excellence progran, Exactis Innovations, and the Fonds de recherche du Québec - Santé, Axe cancer du sein et de l'ovaire (FRSQ-ACSO).

History