TY - JOUR
T1 - Analysis of 1508 Plasma Samples by Capillary-Flow Data-Independent Acquisition Profiles Proteomics of Weight Loss and Maintenance
AU - Bruderer, Roland
AU - Muntel, Jan
AU - Muller, Sebastian
AU - Bernhard, Oliver M.
AU - Gandhi, Tejas
AU - Cominetti, Ornella
AU - Macron, Charlotte
AU - Carayol, Jerome
AU - Rinner, Oliver
AU - Astrup, Arne
AU - Saris, Wim H. M.
AU - Hager, Jorg
AU - Valsesia, Armand
AU - Dayon, Loic
AU - Reiter, Lukas
N1 - Funding Information:
Competing financial interests: The authors R.B., J.M. S.M., T.G., O.M.B., O.R. and L.R. are full-time employees of Biognosys AG (Zurich, Switzerland). Spectronaut is a trademark of Biognosys AG., O.C., C.M., J.C., J.H., A.V., and L.D. are full-time employees at the Nestlé Institute of Health Sciences., W.H.S. has received research support from several food companies such as Nestlé, DSM, Unilever, Nutrition et Santé and Danone as well as pharmaceutical companies such as Novartis, GSK and Novo Nordisk. He is an unpaid scientific advisor for the International Life Science Institute, ILSI Europe., A.A. has received grants from Arla Foods, DK, Danish Dairy Research Council, Nordea Foundation, DK and McCain Foods, as well as personal fees from McCain Foods, McDonald’s, Basic Research, Nestlé, Lausanne Dutch Beer Knowledge Institute, NL, Gelesis, Novo Nordisk, DK, S-Biotek, DK, all outside the submitted work; and Royalties received for the book first published in Danish as “Verdens Bedste Kur” (Politiken, Copenhagen) and subsequently published in Dutch as “Het beste dieet ter wereld” (Kosmos Uitgevers, Utrecht/Antwerpen), and in English as “World’s Best Diet” (Penguin, Australia). ** To whom correspondence should be addressed: Wagistrasse 21, 8952 Schlieren, Switzerland, Tel.: +41 (0)44 738 20 40; Fax: +41 (0)44 738 20 49; E-mail: [email protected].
Funding Information:
* This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 686282. Jan Muntel was supported by an innovation project grant from Innosuisse (Project Number 18365.2 PFLS-LS). The DiOGenes project was supported by the European Commission (Food Quality and Safety Priority of the Sixth Framework Program: FP6-2005-513946). Local sponsors made financial contributions to the shop centers, which also received a number of foods free of charge from food manufacturers. A full list of these sponsors can be seen at www.DiOGenes-eu.org/sponsors. The funders of the study had no role in study design, data collection, analysis, interpretation, or writing of the manuscript. □S This article contains supplemental Figures and Tables.
Publisher Copyright:
© 2019 Bruderer et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2019/6
Y1 - 2019/6
N2 - Comprehensive, high throughput analysis of the plasma proteome has the potential to enable holistic analysis of the health state of an individual. Based on our own experience and the evaluation of recent large-scale plasma mass spectrometry (MS) based proteomic studies, we identified two outstanding challenges: slow and delicate nano-flow liquid chromatography (LC) and irreproducibility of identification of data-dependent acquisition (DDA). We determined an optimal solution reducing these limitations with robust capillary-flow data-independent acquisition (DIA) MS. This platform can measure 31 plasma proteomes per day. Using this setup, we acquired a largescale plasma study of the diet, obesity and genes dietary (DiOGenes) comprising 1508 samples. Proving the robustness, the complete acquisition was achieved on a single analytical column. Totally, 565 proteins (459 identified with two or more peptide sequences) were profiled with 74% data set completeness. On average 408 proteins (5246 peptides) were identified per acquisition (319 proteins in 90% of all acquisitions). The workflow reproducibility was assessed using 34 quality control pools acquired at regular intervals, resulting in 92% data set completeness with CVs for protein measurements of 10.9%. The profiles of 20 apolipoproteins could be profiled revealing distinct changes. The weight loss and weight maintenance resulted in sustained effects on low-grade inflammation, as well as steroid hormone and lipid metabolism, indicating beneficial effects. Comparison to other largescale plasma weight loss studies demonstrated high robustness and quality of biomarker candidates identified. Tracking of nonenzymatic glycation indicated a delayed, slight reduction of glycation in the weight maintenance phase. Using stable-isotope-references, we could directly and absolutely quantify 60 proteins in the DIA. In conclusion, we present herein the first large-scale plasma DIA study and one of the largest clinical research proteomic studies to date. Application of this fast and robust workflow has great potential to advance biomarker discovery in plasma.
AB - Comprehensive, high throughput analysis of the plasma proteome has the potential to enable holistic analysis of the health state of an individual. Based on our own experience and the evaluation of recent large-scale plasma mass spectrometry (MS) based proteomic studies, we identified two outstanding challenges: slow and delicate nano-flow liquid chromatography (LC) and irreproducibility of identification of data-dependent acquisition (DDA). We determined an optimal solution reducing these limitations with robust capillary-flow data-independent acquisition (DIA) MS. This platform can measure 31 plasma proteomes per day. Using this setup, we acquired a largescale plasma study of the diet, obesity and genes dietary (DiOGenes) comprising 1508 samples. Proving the robustness, the complete acquisition was achieved on a single analytical column. Totally, 565 proteins (459 identified with two or more peptide sequences) were profiled with 74% data set completeness. On average 408 proteins (5246 peptides) were identified per acquisition (319 proteins in 90% of all acquisitions). The workflow reproducibility was assessed using 34 quality control pools acquired at regular intervals, resulting in 92% data set completeness with CVs for protein measurements of 10.9%. The profiles of 20 apolipoproteins could be profiled revealing distinct changes. The weight loss and weight maintenance resulted in sustained effects on low-grade inflammation, as well as steroid hormone and lipid metabolism, indicating beneficial effects. Comparison to other largescale plasma weight loss studies demonstrated high robustness and quality of biomarker candidates identified. Tracking of nonenzymatic glycation indicated a delayed, slight reduction of glycation in the weight maintenance phase. Using stable-isotope-references, we could directly and absolutely quantify 60 proteins in the DIA. In conclusion, we present herein the first large-scale plasma DIA study and one of the largest clinical research proteomic studies to date. Application of this fast and robust workflow has great potential to advance biomarker discovery in plasma.
KW - BIOMARKER DISCOVERY
KW - MASS-SPECTROMETRY
KW - EXPRESSION
KW - PROTEINS
KW - VALIDATION
KW - RECEPTOR
KW - PEPTIDE
KW - RATES
U2 - 10.1074/mcp.RA118.001288
DO - 10.1074/mcp.RA118.001288
M3 - Article
C2 - 30948622
SN - 1535-9476
VL - 18
SP - 1242
EP - 1254
JO - Molecular & Cellular Proteomics
JF - Molecular & Cellular Proteomics
IS - 6
M1 - ARTN RA118.001288
ER -