Analysis of 1508 plasma samples by capillary-flow data-independent acquisition profiles proteomics of weight loss and maintenance

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 - Müller, Sebastian

AU - Bernhardt, Oliver M

AU - Gandhi, Tejas

AU - Cominetti, Ornella

AU - Macron, Charlotte

AU - Carayol, Jérôme

AU - Rinner, Oliver

AU - Astrup, Arne

AU - Saris, Wim H M

AU - Hager, Jorg

AU - Valsesia, Armand

AU - Dayon, Loïc

AU - Reiter, Lukas

N1 - CURIS 2019 NEXS 189 Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2019

Y1 - 2019

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 large-scale 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 large-scale 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.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 large-scale 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 large-scale 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.proteomic studies to date. Application of this fast and robust workflow has great potential to advance biomarker discovery in plasma.

KW - Faculty of Science

KW - Plasma proteomics

KW - Data-independent acquisition

KW - SWATH

KW - Label-free quantification

KW - Stable isotope-based quantification

KW - Library

KW - Single shot

KW - High throughput

KW - clinical proteomics

U2 - 10.1074/mcp.RA118.001288

DO - 10.1074/mcp.RA118.001288

M3 - Journal article

C2 - 30948622

SN - 1535-9476

VL - 18

SP - 1242

EP - 1254

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

IS - 6

ER -