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Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

ABSTRACT: Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

SUBMITTER: Shen B

PROVIDER: S-EPMC7254001 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Shen Bo B Yi Xiao X Sun Yaoting Y Bi Xiaojie X Du Juping J Zhang Chao C Quan Sheng S Zhang Fangfei F Sun Rui R Qian Liujia L Ge Weigang W Liu Wei W Liang Shuang S Chen Hao H Zhang Ying Y Li Jun J Xu Jiaqin J He Zebao Z Chen Baofu B Wang Jing J Yan Haixi H Zheng Yufen Y Wang Donglian D Zhu Jiansheng J Kong Ziqing Z Kang Zhouyang Z Liang Xiao X Ding Xuan X Ruan Guan G Xiang Nan N Cai Xue X Gao Huanhuan H Li Lu L Li Sainan S Xiao Qi Q Lu Tian T Zhu Yi Y Liu Huafen H Chen Haixiao H Guo Tiannan T

Cell 20200528 1

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employe ...[more]

PMID: 32492406

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Project description:BackgroundThe pathogenesis of moyamoya disease (MMD) is unclear. Inflammation and immune imbalance have been identified as potential factors contributing to the occurrence and progression of MMD. However, the specific proteins and metabolites responsible for triggering this process are yet to be established. The purpose of this study is to identify differentially expressed proteins and metabolites in patients with MMD and perform Kyoto Encyclopedia of Genes and Genomes pathway integration analysis to pinpoint crucial proteins and metabolites involved in the disease.MethodsWe performed untargeted metabolomic and data-independent acquisition proteomic analyses on the serum samples of individuals with MMD and healthy controls (HC).ResultsIn patients with MMD versus HC, 24 proteins and 60 metabolites, including 21 anionic metabolites and 39 cationic metabolites, which were significantly different, were identified. In patients with MMD, several proteins involved in inflammation and immune metabolism, such as tubulin beta-6 and complement C4, were found to have significantly altered levels. Similarly, many metabolites involved in inflammation and immune metabolisms, such as dimethyl 4-hydroxyisophthalate, beta-nicotinamide mononucleotide, 2-(3-(4-pyridyl)-1H-1,2,4-triazol-5-yl)pyridine, and PC (17:1/18:2), were significantly altered. Intriguingly, these proteins and metabolites are involved in the progression of atherosclerosis through immune and inflammatory pathways, although some have never been reported in MMD. Moreover, integrated proteomics and metabolomics studies were conducted to determine shared pathways involving cholesterol metabolism, vitamin digestion, fat digestion, and absorption pathways of proteins and metabolites, which warrant further investigation.ConclusionsSignificant increases in pro-inflammatory and immunosuppressive abilities have been observed in patients with MMD, accompanied by significant reductions in anti-inflammatory and immune regulation. Various metabolites and proteins implicated in these processes have been identified for the first time. These findings hold immense significance for comprehending the pathogenesis of MMD and for the development of future drug therapies.

Dataset Information

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Publications

Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

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