Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity.
Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity.
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DOI：
10.1016/j.cels.2022.06.006
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发表时间：
2022-08-17
期刊：
影响因子：
9.3
通讯作者：
中科院分区：
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--
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2019冠状病毒病（COVID-19）的临床结局和疾病严重程度是异质性的，疾病的进展或死亡不能用年龄或合并症等单一因素来解释。在这项研究中，我们使用全血RNA测序、流式细胞术免疫表型、血浆代谢组学和单核细胞单细胞代谢组学等系统范围的基于网络的系统生物学分析，在个性化和群体水平上确定COVID-19严重程度的潜在决定因素。单核吞噬细胞的数字细胞定量和免疫表型分析表明，在协调介导COVID-19严重程度的免疫细胞中发挥重要作用。分层特异性和个性化基因组尺度代谢模型表明，单羧酸转运蛋白家族基因（如SLC16A6）、核苷转运蛋白基因（如SLC29A1）以及代谢物如α-酮戊二酸盐、琥珀酸盐、苹果酸盐和丁酸盐可能在COVID-19严重程度中发挥关键作用。针对中枢代谢途径（TCA循环）的代谢扰动可作为重症COVID-19的替代治疗策略。Ambikan等人使用血细胞转录组学、免疫表型、血浆代谢组学和单核细胞的单细胞型代谢组学来鉴定COVID-19患者系统水平的代谢重新连接。整合组学改进了COVID-19严重程度风险组的临床定义。个性化和群体特异性代谢模型表明，中枢代谢（TCA循环）转运体和代谢物在COVID-19严重程度中发挥重要作用。这可能导致重症COVID-19患者通过中枢代谢紊乱而采取替代治疗策略。
The clinical outcome and disease severity in coronavirus disease 2019 (COVID-19) are heterogeneous, and the progression or fatality of the disease cannot be explained by a single factor like age or comorbidities. In this study, we used system-wide network-based system biology analysis using whole blood RNA sequencing, immunophenotyping by flow cytometry, plasma metabolomics, and single-cell-type metabolomics of monocytes to identify the potential determinants of COVID-19 severity at personalized and group levels. Digital cell quantification and immunophenotyping of the mononuclear phagocytes indicated a substantial role in coordinating the immune cells that mediate COVID-19 severity. Stratum-specific and personalized genome-scale metabolic modeling indicated monocarboxylate transporter family genes (e.g., SLC16A6), nucleoside transporter genes (e.g., SLC29A1), and metabolites such as α-ketoglutarate, succinate, malate, and butyrate could play a crucial role in COVID-19 severity. Metabolic perturbations targeting the central metabolic pathway (TCA cycle) can be an alternate treatment strategy in severe COVID-19. Ambikan et al. used blood cell transcriptomics, immunophenotyping, plasma metabolomics, and single-cell-type metabolomics of monocytes to identify the system-level metabolic rewiring in COVID-19 patients. Integrative omics improved the clinical definition of the risk group of COVID-19 severity. The personalized and group-specific metabolic models indicated the essential role of transporters and metabolites of central metabolism (TCA cycle) in COVID-19 severity. This can lead to an alternate treatment strategy through metabolic perturbations of central metabolism in severe COVID-19.
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影响因子：
8
作者：
Bohnacker, Sina;Hartung, Franziska;Henkel, Fiona;Quaranta, Alessandro;Kolmert, Johan;Priller, Alina;Ud-Dean, Minhaz;Giglberger, Johanna;Kugler, Luisa M.;Pechtold, Lisa;Yazici, Sarah;Lechner, Antonie;Erber, Johanna;Protzer, Ulrike;Lingor, Paul;Knolle, Percy;Chaker, Adam M.;Schmidt-Weber, Carsten B.;Wheelock, Craig E.;Esser-von Bieren, Julia
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