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Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity
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- Ambikan, Anoop T. (author)
- Karolinska Institutet
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- Yang, Hong (author)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Krishnan, Shuba (author)
- Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Syst Virol Lab, Stockholm S-14152, Sweden.
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- (creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
- In: Cell systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 13:8, s. 665-681
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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 metabolo-mics 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 sub-stantial role in coordinating the immune cells that mediate COVID-19 severity. Stratum-specific and person-alized genome-scale metabolic modeling indicated monocarboxylate transporter family genes (e.g., SLC16A6), nucleoside transporter genes (e.g., SLC29A1), and metabolites such as a-ketoglutarate, succi-nate, 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- COVID-19
- similarity network fusion
- personalized genome-scale metabolic model
Publication and Content Type
- ref (subject category)
- art (subject category)
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- About the subject
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- NATURAL SCIENCES
- NATURAL SCIENCES
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- Articles in the publication
- Cell systems
- By the university
- Stockholm University
- Royal Institute of Technology
- Karolinska Institutet
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