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Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection.
Cell Systems ( IF 9.3 ) Pub Date : 2020-06-02 , DOI: 10.1016/j.cels.2020.05.012
Christoph B Messner 1 , Vadim Demichev 2 , Daniel Wendisch 3 , Laura Michalick 4 , Matthew White 1 , Anja Freiwald 5 , Kathrin Textoris-Taube 6 , Spyros I Vernardis 1 , Anna-Sophia Egger 1 , Marco Kreidl 1 , Daniela Ludwig 7 , Christiane Kilian 7 , Federica Agostini 7 , Aleksej Zelezniak 8 , Charlotte Thibeault 3 , Moritz Pfeiffer 3 , Stefan Hippenstiel 3 , Andreas Hocke 3 , Christof von Kalle 9 , Archie Campbell 10 , Caroline Hayward 11 , David J Porteous 12 , Riccardo E Marioni 12 , Claudia Langenberg 13 , Kathryn S Lilley 14 , Wolfgang M Kuebler 4 , Michael Mülleder 6 , Christian Drosten 15 , Norbert Suttorp 3 , Martin Witzenrath 3 , Florian Kurth 16 , Leif Erik Sander 3 , Markus Ralser 17
Affiliation  

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.



中文翻译:

超高通量临床蛋白质组学揭示了 COVID-19 感染的分类。

COVID-19 大流行是前所未有的全球挑战,迫切需要即时诊断分类器。在这里,我们提出了一个基于 ISO13485 标准化的超高通量血清和血浆蛋白质组学平台,以方便在受监管的临床实验室中简单实施。我们的低成本工作流程每天可处理多达 180 个样本,实现高精度定量,并减少大规模纵向研究的批次效应。我们使用我们的平台对从 SARS-CoV-2 大流行的早期住院病例中收集的样本进行分析,并识别出 27 种潜在的生物标志物,这些标志物的表达根据 WHO 的 COVID-19 严重程度而有所不同。它们包括补体因子、凝血系统、炎症调节剂以及白细胞介素 6 上游和下游的促炎因子。用于实施我们方法的所有协议和软件都是免费提供的。总的来说,这项工作支持常规蛋白质组学检测的开发,以帮助临床决策并生成有关潜在 COVID-19 治疗靶点的假设。

更新日期:2020-06-02
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