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全面蛋白质组学和 COVID-19 宿主反应的荟萃分析。

Comprehensive proteomics and meta-analysis of COVID-19 host response.

机构信息

Science for Life Laboratory and Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

Centre for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.

出版信息

Nat Commun. 2023 Sep 22;14(1):5921. doi: 10.1038/s41467-023-41159-z.

DOI:10.1038/s41467-023-41159-z
PMID:37739942
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10516886/
Abstract

COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community.

摘要

COVID-19 的特征是人体系统性免疫紊乱,可导致多器官损伤。这些过程中的许多被认为是由血液介导的。因此,为了更好地了解人体对 SARS-CoV-2 感染的系统性宿主反应,我们通过 MS 蛋白质组学对血液中的循环可溶性蛋白质进行了系统分析。在这里,我们表明,在 COVID-19 中,大部分可溶性血液蛋白质组发生了改变,其中干扰素诱导和蛋白酶体蛋白的水平升高。一些在体外 SARS-CoV-2 感染后和 COVID-19 患者不同器官中人类细胞中水平交替的蛋白质在血液中失调,表明存在共同的感染相关变化。由于不同的可溶性血液蛋白质组改变的公共蛋白质组学资源的可用性,使得在 COVID-19 期间给定蛋白质变化的不确定性。因此,我们对可溶性血液蛋白质组的 MS 全局蛋白质组学研究进行了系统综述和荟萃分析,其中包括多达 1706 个人(1039 例 COVID-19 患者),以提供 COVID-19 中 1517 种可溶性血液蛋白质变化的结论估计。最后,基于荟萃分析,我们开发了 CoViMAPP,这是一个用于 COVID-19 中可溶性血液蛋白质改变的效应大小和诊断潜力的开放访问资源,可供研究、临床和学术界使用。

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