Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection

被引：384

作者：

Messner, Christoph B. ^{[1
]}

Demichev, Vadim ^{[1
,2
]}

Wendisch, Daniel ^{[3
]}

Michalick, Laura ^{[4
]}

White, Matthew ^{[1
]}

Freiwald, Anja ^{[5
,6
]}

Textoris-Taube, Kathrin ^{[5
]}

Vernardis, Spyros, I ^{[1
]}

Egger, Anna-Sophia ^{[1
]}

Kreidl, Marco ^{[1
]}

Ludwig, Daniela ^{[6
]}

Kilian, Christiane ^{[6
]}

Agostini, Federica ^{[6
]}

Zelezniak, Aleksej ^{[1
,7
]}

Thibeault, Charlotte ^{[3
]}

Pfeiffer, Moritz ^{[3
]}

Hippenstiel, Stefan ^{[3
]}

Hocke, Andreas ^{[3
]}

von Kalle, Christof ^{[8
,9
]}

Campbell, Archie ^{[10
,11
]}

Hayward, Caroline ^{[12
]}

Porteous, David J. ^{[10
]}

Marioni, Riccardo E. ^{[10
]}

Langenberg, Claudia ^{[1
,13
]}

Lilley, Kathryn S. ^{[2
]}

Kuebler, Wolfgang M. ^{[4
]}

Muelleder, Michael ^{[5
]}

Drosten, Christian ^{[14
]}

Suttorp, Norbert ^{[3
]}

Witzenrath, Martin ^{[3
]}

Kurth, Florian ^{[3
,15
]}

Sander, Leif Erik ^{[3
]}

Ralser, Markus ^{[1
,6
]}

机构：

[1] Francis Crick Inst, Mol Biol Metab Lab, London NW1 1AT, England

[2] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England

[3] Charite, Dept Infect Dis & Resp Med, D-10117 Berlin, Germany

[4] Charite, Inst Physiol, D-10117 Berlin, Germany

[5] Charite, Core Facil High Throughput Mass Spectrometry, D-10117 Berlin, Germany

[6] Charite, Dept Biochem, D-10117 Berlin, Germany

[7] Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden

[8] Berlin Inst Hlth BIH, D-10117 Berlin, Germany

[9] Charite, Clin Study Ctr CSC, D-10117 Berlin, Germany

[10] Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland

[11] Univ Edinburgh, Usher Inst, 9 Edinburgh Bioquarter,9 Little France Rd, Edinburgh EH16 4UX, Midlothian, Scotland

[12] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[13] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England

[14] Charite, Dept Virol, D-10117 Berlin, Germany

[15] Bernhard Nocht Inst Trop Med, Dept Trop Med, Hamburg, Germany

来源：

CELL SYSTEMS | 2020年 / 11卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

LIPOPOLYSACCHARIDE-BINDING PROTEIN; LRG1 PROMOTES ANGIOGENESIS; PLASMA PROTEOME; IMMUNE EVASION; CD14; EXPRESSION; GELSOLIN; STRATEGIES; PATHWAY; MARKER;

D O I：

10.1016/j.cels.2020.05.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up to 180 samples per day, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, this work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.

引用

页码：11 / +

页数：18

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