Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity.
COVID-19
personalized genome-scale metabolic model
similarity network fusion
Journal
Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080
Informations de publication
Date de publication:
17 08 2022
17 08 2022
Historique:
received:
08
12
2021
revised:
18
04
2022
accepted:
27
06
2022
pubmed:
8
8
2022
medline:
23
8
2022
entrez:
7
8
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35933992
pii: S2405-4712(22)00276-9
doi: 10.1016/j.cels.2022.06.006
pmc: PMC9263811
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
665-681.e4Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Nat Methods. 2014 Mar;11(3):333-7
pubmed: 24464287
J Biol Chem. 2022 Apr;298(4):101800
pubmed: 35257743
J Infect Dis. 2020 Aug 17;222(6):894-898
pubmed: 32582936
Nucleic Acids Res. 2013 Apr;41(8):4378-91
pubmed: 23444143
Crit Rev Immunol. 2012;32(2):139-55
pubmed: 23216612
Pharmacol Rev. 2020 Jan;72(1):343-379
pubmed: 31882442
Life Sci Alliance. 2022 May 10;5(9):
pubmed: 35537851
Annu Rev Nutr. 2017 Aug 21;37:51-76
pubmed: 28826372
Life Sci Alliance. 2021 Aug 5;4(10):
pubmed: 34353886
Sci Rep. 2021 Jul 1;11(1):13637
pubmed: 34211032
Int J Infect Dis. 2021 Feb;103:25-32
pubmed: 33186704
J Cell Mol Med. 2020 Oct;24(19):11603-11606
pubmed: 32864865
Immun Ageing. 2019 Jan 26;16:3
pubmed: 30700992
Mol Syst Biol. 2014 Mar 19;10:721
pubmed: 24646661
Sci Signal. 2020 Mar 24;13(624):
pubmed: 32209698
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2247-52
pubmed: 24390544
Front Immunol. 2021 Jun 28;12:700782
pubmed: 34262570
Adv Nutr. 2018 Jan 1;9(1):21-29
pubmed: 29438462
Nat Commun. 2021 Jul 5;12(1):4117
pubmed: 34226537
Mol Cell Proteomics. 2021;20:100159
pubmed: 34619366
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
Nat Med. 2020 Jun;26(6):842-844
pubmed: 32398875
PLoS Comput Biol. 2012;8(5):e1002518
pubmed: 22615553
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Mucosal Immunol. 2022 Mar;15(3):515-524
pubmed: 35288643
Front Immunol. 2021 Jul 30;12:700152
pubmed: 34394094
Database (Oxford). 2019 Jan 1;2019:
pubmed: 30951143
Mol Syst Biol. 2009;5:323
pubmed: 19888218
J R Soc Interface. 2018 Sep 12;15(146):
pubmed: 30209043
Emerg Microbes Infect. 2020 Dec;9(1):1748-1760
pubmed: 32691695
Methods Mol Biol. 2020;2120:233-248
pubmed: 32124324
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):
pubmed: 33479167
Bioinformatics. 2020 Dec 30;36(Suppl 2):i813-i821
pubmed: 33381848
Science. 2017 Apr 21;356(6335):
pubmed: 28428369
Comput Struct Biotechnol J. 2021;19:976-988
pubmed: 33558827
Mol Aspects Med. 2013 Apr-Jun;34(2-3):337-49
pubmed: 23506875
Front Immunol. 2021 Jun 23;12:691725
pubmed: 34248984
Nat Protoc. 2019 Mar;14(3):639-702
pubmed: 30787451
J Mol Cell Biol. 2019 Jan 1;11(1):1-13
pubmed: 30239845
Mol Syst Biol. 2020 May;16(5):e8982
pubmed: 32463598
Front Pharmacol. 2021 Feb 04;11:600369
pubmed: 33613280
Trends Microbiol. 2011 Jul;19(7):360-7
pubmed: 21570293
PLoS Pathog. 2021 Jul 6;17(7):e1009721
pubmed: 34228753
FEBS Lett. 2021 Sep;595(18):2350-2365
pubmed: 34409594
Microbiol Spectr. 2021 Oct 31;9(2):e0054921
pubmed: 34468185
Anal Biochem. 2004 Aug 15;331(2):283-95
pubmed: 15265734
Bioinformatics. 2016 Sep 15;32(18):2847-9
pubmed: 27207943
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Nucleic Acids Res. 2019 Jan 8;47(D1):D721-D728
pubmed: 30289549
JCI Insight. 2020 Jul 23;5(14):
pubmed: 32559180
Science. 2017 Aug 18;357(6352):
pubmed: 28818916
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Natl Sci Rev. 2020 Jul;7(7):1157-1168
pubmed: 34676128
Cell Death Differ. 2020 Nov;27(11):3196-3207
pubmed: 32514047
Am J Physiol Lung Cell Mol Physiol. 2013 Nov 15;305(10):L702-11
pubmed: 24056971
Scand J Immunol. 2022 Jan;95(1):e13108
pubmed: 34625989
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cell Metab. 2020 Sep 1;32(3):498-499
pubmed: 32877692
EMBO J. 2020 Dec 15;39(24):e105896
pubmed: 33140861
Front Immunol. 2021 Mar 25;12:652470
pubmed: 33841435
J Clin Invest. 2021 Mar 15;131(6):
pubmed: 33492309
PLoS Comput Biol. 2018 Oct 18;14(10):e1006541
pubmed: 30335785
Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):E8929-E8938
pubmed: 30181265
Sci Rep. 2019 Mar 26;9(1):5233
pubmed: 30914743
Proc Natl Acad Sci U S A. 2021 Oct 5;118(40):
pubmed: 34548411
Front Immunol. 2021 May 24;12:665773
pubmed: 34108966
Cell. 2020 Sep 17;182(6):1419-1440.e23
pubmed: 32810438
JCI Insight. 2020 Jun 4;5(11):
pubmed: 32329756
Biomed Pharmacother. 2021 Dec;144:112346
pubmed: 34678727
Front Immunol. 2019 Dec 13;10:2759
pubmed: 31921102
Nat Biotechnol. 2020 Aug;38(8):970-979
pubmed: 32591762
Nat Cell Biol. 2021 May;23(5):538-551
pubmed: 33972731
Nat Biotechnol. 2014 Sep;32(9):896-902
pubmed: 25150836
Cell Host Microbe. 2020 Jun 10;27(6):992-1000.e3
pubmed: 32320677
Gut Microbes. 2022 Jan-Dec;14(1):2073131
pubmed: 35574937
Nature. 2021 Jul;595(7865):107-113
pubmed: 33915569
Virol J. 2019 Oct 29;16(1):124
pubmed: 31665046
Cell. 2020 Jul 9;182(1):59-72.e15
pubmed: 32492406
Circ Cardiovasc Genet. 2012 Feb 1;5(1):7-9
pubmed: 22337925
BMC Bioinformatics. 2011 Jan 26;12:35
pubmed: 21269502
Sci Immunol. 2020 Sep 28;5(51):
pubmed: 32989174
Nat Immunol. 2020 Sep;21(9):1107-1118
pubmed: 32788748