Multiomics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity

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dc.contributor.authorAmbikan, Anoop T.
dc.contributor.authorYang, Hong
dc.contributor.authorKrishnan, Shuba
dc.contributor.authorSvensson Akusjärvi, Sara
dc.contributor.authorGupta, Soham
dc.contributor.authorLourda, Magda
dc.contributor.authorSperk, Maike
dc.contributor.authorArif, Muhammad
dc.contributor.authorZhang, Cheng
dc.contributor.authorNordqvist, Hampus
dc.contributor.authorPonnan, Sivasankaran Munusamy
dc.contributor.authorSönnerborg, Anders
dc.contributor.authorTreutiger, Carl Johan
dc.contributor.authorO'Mahony, Liam
dc.contributor.authorMardinoglu, Adil
dc.contributor.authorBenfeitas, Rui
dc.contributor.authorNeogi, Ujjwal
dc.contributor.funderVetenskapsrådeten
dc.contributor.funderKarolinska Instituteten
dc.contributor.funderCenter for Medical Innovationen
dc.contributor.funderÅke Wiberg Stiftelseen
dc.date.accessioned2022-07-12T15:02:51Z
dc.date.available2022-07-12T15:02:51Z
dc.date.issued2022-07-08
dc.date.updated2022-07-12T14:31:33Z
dc.description.abstractThe 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.en
dc.description.sponsorshipVetenskapsrådet (grants 2021-00993; 2017-01330; 2018-06156; 2021-03035) Karolinska Institutet (grant 2020-01554; 2020-02153); Center for Medical Innovation (grant CIMED-FoUI-093304); Åke Wiberg Stiftelse (grant M20-0220)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationAmbikan, 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, 13(8), pp.665-681. https://doi.org/10.1016/j.cels.2022.06.006en
dc.identifier.doi10.1016/j.cels.2022.06.006en
dc.identifier.eissn2405-4712
dc.identifier.endpage681
dc.identifier.issued8
dc.identifier.journaltitleCell Systemsen
dc.identifier.startpage665
dc.identifier.urihttps://hdl.handle.net/10468/13358
dc.identifier.volume13
dc.language.isoenen
dc.publisherElsevier B.V.en
dc.rights© 2021, Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectMultiomics personalized network analysesen
dc.subjectProgressive disruptionen
dc.subjectCentral metabolismen
dc.subjectCOVID-19en
dc.subjectSeverityen
dc.titleMultiomics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severityen
dc.typeArticle (peer-reviewed)en
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