tetano
Editor, Senior Moderator
Cell Syst
. 2022 Jul 8;S2405-4712(22)00276-9.
doi: 10.1016/j.cels.2022.06.006. Online ahead of print.
Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity
Anoop T Ambikan[SUP] 1 [/SUP], Hong Yang[SUP] 2 [/SUP], Shuba Krishnan[SUP] 1 [/SUP], Sara Svensson Akusjärvi[SUP] 1 [/SUP], Soham Gupta[SUP] 1 [/SUP], Magda Lourda[SUP] 3 [/SUP], Maike Sperk[SUP] 1 [/SUP], Muhammad Arif[SUP] 2 [/SUP], Cheng Zhang[SUP] 2 [/SUP], Hampus Nordqvist[SUP] 4 [/SUP], Sivasankaran Munusamy Ponnan[SUP] 5 [/SUP], Anders Sönnerborg[SUP] 6 [/SUP], Carl Johan Treutiger[SUP] 7 [/SUP], Liam O'Mahony[SUP] 8 [/SUP], Adil Mardinoglu[SUP] 9 [/SUP], Rui Benfeitas[SUP] 10 [/SUP], Ujjwal Neogi[SUP] 11 [/SUP]
Affiliations
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, 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.
Keywords: COVID-19; personalized genome-scale metabolic model; similarity network fusion.
. 2022 Jul 8;S2405-4712(22)00276-9.
doi: 10.1016/j.cels.2022.06.006. Online ahead of print.
Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity
Anoop T Ambikan[SUP] 1 [/SUP], Hong Yang[SUP] 2 [/SUP], Shuba Krishnan[SUP] 1 [/SUP], Sara Svensson Akusjärvi[SUP] 1 [/SUP], Soham Gupta[SUP] 1 [/SUP], Magda Lourda[SUP] 3 [/SUP], Maike Sperk[SUP] 1 [/SUP], Muhammad Arif[SUP] 2 [/SUP], Cheng Zhang[SUP] 2 [/SUP], Hampus Nordqvist[SUP] 4 [/SUP], Sivasankaran Munusamy Ponnan[SUP] 5 [/SUP], Anders Sönnerborg[SUP] 6 [/SUP], Carl Johan Treutiger[SUP] 7 [/SUP], Liam O'Mahony[SUP] 8 [/SUP], Adil Mardinoglu[SUP] 9 [/SUP], Rui Benfeitas[SUP] 10 [/SUP], Ujjwal Neogi[SUP] 11 [/SUP]
Affiliations
- PMID: 35933992
- DOI: 10.1016/j.cels.2022.06.006
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, 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.
Keywords: COVID-19; personalized genome-scale metabolic model; similarity network fusion.