Multiomics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity
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Accepted Version
Date
2022-07-08
Authors
Ambikan, Anoop T.
Yang, Hong
Krishnan, Shuba
Svensson Akusjärvi, Sara
Gupta, Soham
Lourda, Magda
Sperk, Maike
Arif, Muhammad
Zhang, Cheng
Nordqvist, Hampus
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier B.V.
Published Version
Abstract
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, immune-phenotyping by flow cytometry, plasma metabolomics, and single cell-type metabolomics of the monocytes to identify the potential determinants of COVID-19 severity at the personalized and group level. Digital cell quantification and immune-phenotyping of the mononuclear phagocytes indicated a substantial role in coordinating the immune cells that mediate the 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.
Description
Keywords
Multiomics personalized network analyses , Progressive disruption , Central metabolism , COVID-19 , Severity
Citation
Ambikan, A. T., Krishnan, S., Yang, H., Svensson Akusjärvi, S., Gupta, S., Lourda, M., Sperk, M., Arif, M., Zhang, C., Nordqvist, H., Ponnan, S. M., Sönnerborg, A., Treutiger, C. J., O’Mahony, L., Mardinoglu, A., Benfeitas, R. and Neogi, U. (2022) 'Multiomics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity', Cell Systems. doi: 10.1016/j.cels.2022.06.006