Display options
Cite
Hasankhani A, Bahrami A, Sheybani N, et al. Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic. Front Immunol. 2021;12:789317doi: 10.3389/fimmu.2021.789317.
Hasankhani, A., Bahrami, A., Sheybani, N., Aria, B., Hemati, B., Fatehi, F., Ghaem Maghami Farahani, H., Javanmard, G., Rezaee, M., Kastelic, J. P., & Barkema, H. W. (2021). Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic. Frontiers in immunology, 12789317. https://doi.org/10.3389/fimmu.2021.789317
Hasankhani, Aliakbar, et al. "Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic." Frontiers in immunology vol. 12 (2021): 789317. doi: https://doi.org/10.3389/fimmu.2021.789317
Hasankhani A, Bahrami A, Sheybani N, Aria B, Hemati B, Fatehi F, Ghaem Maghami Farahani H, Javanmard G, Rezaee M, Kastelic JP, Barkema HW. Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic. Front Immunol. 2021 Dec 15;12:789317. doi: 10.3389/fimmu.2021.789317. eCollection 2021. PMID: 34975885; PMCID: PMC8714803.
Copy Download .nbib Format: NLM
Share it on

Front Immunol. 2021 Dec 15;12:789317. doi: 10.3389/fimmu.2021.789317. eCollection 2021.

Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic.

Frontiers in immunology

Aliakbar Hasankhani, Abolfazl Bahrami, Negin Sheybani, Behzad Aria, Behzad Hemati, Farhang Fatehi, Hamid Ghaem Maghami Farahani, Ghazaleh Javanmard, Mahsa Rezaee, John P Kastelic, Herman W Barkema

Affiliations

  1. Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, Iran.
  2. Biomedical Center for Systems Biology Science Munich, Ludwig-Maximilians-University, Munich, Germany.
  3. Department of Animal and Poultry Science, College of Aburaihan, University of Tehran, Tehran, Iran.
  4. Department of Physical Education and Sports Science, School of Psychology and Educational Sciences, Yazd University, Yazd, Iran.
  5. Biotechnology Research Center, Karaj Branch, Islamic Azad University, Karaj, Iran.
  6. Department of Medical Mycology, School of Medical Science, Tarbiat Modares University, Tehran, Iran.
  7. Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.

PMID: 34975885 PMCID: PMC8714803 DOI: 10.3389/fimmu.2021.789317

Abstract

BACKGROUND: The recent emergence of COVID-19, rapid worldwide spread, and incomplete knowledge of molecular mechanisms underlying SARS-CoV-2 infection have limited development of therapeutic strategies. Our objective was to systematically investigate molecular regulatory mechanisms of COVID-19, using a combination of high throughput RNA-sequencing-based transcriptomics and systems biology approaches.

METHODS: RNA-Seq data from peripheral blood mononuclear cells (PBMCs) of healthy persons, mild and severe 17 COVID-19 patients were analyzed to generate a gene expression matrix. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules in healthy samples as a reference set. For differential co-expression network analysis, module preservation and module-trait relationships approaches were used to identify key modules. Then, protein-protein interaction (PPI) networks, based on co-expressed hub genes, were constructed to identify hub genes/TFs with the highest information transfer (hub-high traffic genes) within candidate modules.

RESULTS: Based on differential co-expression network analysis, connectivity patterns and network density, 72% (15 of 21) of modules identified in healthy samples were altered by SARS-CoV-2 infection. Therefore, SARS-CoV-2 caused systemic perturbations in host biological gene networks. In functional enrichment analysis, among 15 non-preserved modules and two significant highly-correlated modules (identified by MTRs), 9 modules were directly related to the host immune response and COVID-19 immunopathogenesis. Intriguingly, systemic investigation of SARS-CoV-2 infection identified signaling pathways and key genes/proteins associated with COVID-19's main hallmarks, e.g., cytokine storm, respiratory distress syndrome (ARDS), acute lung injury (ALI), lymphopenia, coagulation disorders, thrombosis, and pregnancy complications, as well as comorbidities associated with COVID-19, e.g., asthma, diabetic complications, cardiovascular diseases (CVDs), liver disorders and acute kidney injury (AKI). Topological analysis with betweenness centrality (BC) identified 290 hub-high traffic genes, central in both co-expression and PPI networks. We also identified several transcriptional regulatory factors, including

CONCLUSION: This study provides comprehensive information on molecular mechanisms of SARS-CoV-2-host interactions and identifies several hub-high traffic genes as promising therapeutic targets for the COVID-19 pandemic.

Copyright © 2021 Hasankhani, Bahrami, Sheybani, Aria, Hemati, Fatehi, Ghaem Maghami Farahani, Javanmard, Rezaee, Kastelic and Barkema.

Keywords: COVID-19 pandemic; WGCNA; hub-high traffic genes; immunopathogenesis; systems biology; systems immunology; therapeutic targets in infectious diseases

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Mol Divers. 2021 Jun 9;: - PubMed
  2. J Formos Med Assoc. 2021 Jun 19;: - PubMed
  3. Front Aging Neurosci. 2021 Jan 12;12:614650 - PubMed
  4. Nat Commun. 2021 Aug 26;12(1):5148 - PubMed
  5. Front Public Health. 2020 Jun 18;8:299 - PubMed
  6. PLoS One. 2016 Jun 03;11(6):e0156006 - PubMed
  7. Nat Rev Cardiol. 2021 May;18(5):313-330 - PubMed
  8. Bioinformatics. 2015 Jan 15;31(2):166-9 - PubMed
  9. Neuroscientist. 2021 Aug;27(4):331-339 - PubMed
  10. Brief Bioinform. 2021 Sep 2;22(5): - PubMed
  11. Pharmacol Res. 2021 Jan;163:105297 - PubMed
  12. Immunother Adv. 2021 Jun 02;1(1):ltab013 - PubMed
  13. Int J Mol Sci. 2021 Aug 12;22(16): - PubMed
  14. Front Immunol. 2021 Jul 12;12:701085 - PubMed
  15. Front Immunol. 2020 Dec 09;11:590459 - PubMed
  16. Pharmacol Res. 2020 Jun;156:104808 - PubMed
  17. Int J Infect Dis. 2021 Feb;103:25-32 - PubMed
  18. J Med Virol. 2021 May;93(5):2867-2874 - PubMed
  19. Infect Genet Evol. 2021 Aug;92:104892 - PubMed
  20. Hereditas. 2019 Jan 28;156:7 - PubMed
  21. Front Genet. 2021 Oct 18;12:753839 - PubMed
  22. Nature. 2006 May 11;441(7090):235-8 - PubMed
  23. BMC Pulm Med. 2020 Nov 16;20(1):301 - PubMed
  24. Int Rev Immunol. 2021;40(1-2):72-107 - PubMed
  25. Nat Commun. 2020 Aug 6;11(1):3924 - PubMed
  26. Front Immunol. 2020 Oct 08;11:589380 - PubMed
  27. Methods. 2021 Aug 27;: - PubMed
  28. Front Immunol. 2020 Aug 18;11:2063 - PubMed
  29. Int Immunopharmacol. 2021 Jul;96:107777 - PubMed
  30. BMC Syst Biol. 2012 Apr 30;6:28 - PubMed
  31. Front Immunol. 2021 Mar 04;12:598799 - PubMed
  32. J Med Virol. 2021 Jul;93(7):4576-4584 - PubMed
  33. J Infect Dis. 2021 Feb 13;223(3):536-537 - PubMed
  34. Int J Antimicrob Agents. 2020 May;55(5):105954 - PubMed
  35. PLoS One. 2021 Sep 10;16(9):e0256899 - PubMed
  36. BMC Syst Biol. 2014;8 Suppl 4:S11 - PubMed
  37. Front Pharmacol. 2021 Feb 26;12:598925 - PubMed
  38. Autophagy. 2021 Sep;17(9):2659-2661 - PubMed
  39. J Biomol Struct Dyn. 2021 Jan 28;:1-12 - PubMed
  40. Sci Rep. 2021 Mar 18;11(1):6357 - PubMed
  41. Front Immunol. 2021 Jun 28;12:700782 - PubMed
  42. Arch Pharm Res. 2021 Jan;44(1):99-116 - PubMed
  43. Blood. 2020 Sep 3;136(10):1169-1179 - PubMed
  44. EBioMedicine. 2021 Mar;65:103262 - PubMed
  45. Front Immunol. 2021 Jun 11;12:650465 - PubMed
  46. Med (N Y). 2020 Dec 18;1(1):90-102 - PubMed
  47. Front Genet. 2019 Nov 13;10:1142 - PubMed
  48. Arthritis Res Ther. 2004;6(4):R326-34 - PubMed
  49. Expert Opin Investig Drugs. 2020 Jul;29(7):633-637 - PubMed
  50. Brief Bioinform. 2021 Sep 09;: - PubMed
  51. Clin Infect Dis. 2020 Nov 19;71(16):2052-2060 - PubMed
  52. Am J Reprod Immunol. 2020 Nov;84(5):e13304 - PubMed
  53. Front Microbiol. 2021 May 14;12:675419 - PubMed
  54. BMC Bioinformatics. 2013 Apr 15;14:128 - PubMed
  55. J Cell Biochem. 2019 Jun;120(6):10855-10863 - PubMed
  56. Mol Med Rep. 2017 Nov;16(5):6499-6505 - PubMed
  57. Brief Bioinform. 2021 Mar 22;22(2):1161-1174 - PubMed
  58. J Infect. 2020 Oct;81(4):e11-e17 - PubMed
  59. Cell Rep. 2021 Mar 16;34(11):108863 - PubMed
  60. Front Immunol. 2021 Jul 29;12:716075 - PubMed
  61. Cell. 2002 Feb 22;108(4):557-72 - PubMed
  62. PLoS Comput Biol. 2011 Jan 20;7(1):e1001057 - PubMed
  63. Cell Death Dis. 2021 Jul 23;12(8):732 - PubMed
  64. Sci Rep. 2020 Nov 30;10(1):20834 - PubMed
  65. Front Pharmacol. 2021 Jun 07;12:673485 - PubMed
  66. J Neurovirol. 2020 Oct;26(5):619-630 - PubMed
  67. Front Med (Lausanne). 2021 Jun 22;8:637642 - PubMed
  68. Virulence. 2020 Dec;11(1):1250-1256 - PubMed
  69. Cell Prolif. 2021 May;54(5):e13024 - PubMed
  70. J Med Virol. 2001 Nov;65(3):431-40 - PubMed
  71. J Med Virol. 2021 May;93(5):2735-2739 - PubMed
  72. Pharmacol Res. 2020 Sep;159:105051 - PubMed
  73. Obes Med. 2021 Mar;22:100317 - PubMed
  74. Nat Med. 2021 May;27(5):904-916 - PubMed
  75. Sci Rep. 2018 Jan 12;8(1):622 - PubMed
  76. Sci Rep. 2020 Nov 25;10(1):20533 - PubMed
  77. Int J Mol Sci. 2021 Sep 07;22(18): - PubMed
  78. Cytokine Growth Factor Rev. 2021 Apr;58:102-110 - PubMed
  79. Nat Rev Immunol. 2020 Jul;20(7):397-398 - PubMed
  80. Front Immunol. 2021 Aug 19;12:601080 - PubMed
  81. Front Immunol. 2020 Oct 09;11:590870 - PubMed
  82. Pathol Oncol Res. 2018 Jul;24(3):507-514 - PubMed
  83. Front Pharmacol. 2021 Mar 02;12:646701 - PubMed
  84. Arthritis Rheum. 2000 Nov;43(11):2391-6 - PubMed
  85. Int J Biol Sci. 2020 Mar 15;16(10):1724-1731 - PubMed
  86. Drug Dev Ind Pharm. 2020 Dec;46(12):1947-1959 - PubMed
  87. Int J Mol Sci. 2021 Jun 01;22(11): - PubMed
  88. BMC Bioinformatics. 2012 Dec 09;13:328 - PubMed
  89. Front Cell Dev Biol. 2020 Oct 06;8:545089 - PubMed
  90. Nat Med. 2020 Jun;26(6):842-844 - PubMed
  91. N Engl J Med. 2020 Apr 30;382(18):1708-1720 - PubMed
  92. Am J Clin Pathol. 2004 Apr;121(4):507-11 - PubMed
  93. Cells. 2020 Jul 05;9(7): - PubMed
  94. J Exp Med. 2020 Dec 7;217(12): - PubMed
  95. Front Pharmacol. 2020 Sep 15;11:584057 - PubMed
  96. Sci Rep. 2021 Mar 24;11(1):6725 - PubMed
  97. Rheumatology (Oxford). 2004 Aug;43(8):960-4 - PubMed
  98. Front Immunol. 2020 Jun 16;11:1446 - PubMed
  99. Nat Commun. 2021 Feb 11;12(1):961 - PubMed
  100. Signal Transduct Target Ther. 2021 Jul 30;6(1):292 - PubMed
  101. Autophagy. 2020 Dec;16(12):2276-2281 - PubMed
  102. Infect Genet Evol. 2021 Sep;93:104921 - PubMed
  103. Brief Bioinform. 2021 Nov 5;22(6): - PubMed
  104. Cell Res. 2021 Mar;31(3):272-290 - PubMed
  105. Bioinformatics. 2014 Aug 1;30(15):2114-20 - PubMed
  106. Mol Neurobiol. 2021 Oct;58(10):5356-5368 - PubMed
  107. J Infect Dis. 2020 Jul 23;222(4):556-563 - PubMed
  108. F1000Res. 2020 Nov 19;9:1349 - PubMed
  109. BioData Min. 2020 Nov 10;13(1):19 - PubMed
  110. Chem Biol Interact. 2021 Sep 1;346:109583 - PubMed
  111. J Med Virol. 2021 Apr;93(4):2396-2405 - PubMed
  112. J Exp Med. 2021 Mar 1;218(3): - PubMed
  113. J Med Virol. 2021 Feb;93(2):615-617 - PubMed
  114. Lancet. 2020 May 2;395(10234):1407-1409 - PubMed
  115. Onco Targets Ther. 2020 Jul 12;13:6805-6817 - PubMed
  116. Cell Mol Immunol. 2021 Oct;18(10):2457-2459 - PubMed
  117. Autophagy. 2020 Dec;16(12):2260-2266 - PubMed
  118. Curr Pharmacol Rep. 2020 May 11;:1-15 - PubMed
  119. Nat Commun. 2020 Jul 6;11(1):3434 - PubMed
  120. Clin Infect Dis. 2020 Jul 28;71(15):762-768 - PubMed
  121. Cell. 2020 Mar 19;180(6):1044-1066 - PubMed
  122. Front Pharmacol. 2021 Aug 31;12:688227 - PubMed
  123. Front Immunol. 2020 Dec 07;11:586765 - PubMed
  124. EBioMedicine. 2021 Aug;70:103500 - PubMed
  125. Mediators Inflamm. 2021 Apr 1;2021:6635925 - PubMed
  126. Front Cell Dev Biol. 2021 Jul 27;9:716208 - PubMed
  127. Nat Commun. 2020 Oct 7;11(1):5048 - PubMed
  128. PLoS One. 2011;6(12):e28438 - PubMed
  129. Brief Bioinform. 2021 Nov 5;22(6): - PubMed
  130. Nat Commun. 2021 Aug 26;12(1):5152 - PubMed
  131. Biomedicines. 2021 May 17;9(5): - PubMed
  132. Z Naturforsch C J Biosci. 2021 Aug 05;: - PubMed
  133. Leukemia. 2021 Oct;35(10):3026-3029 - PubMed
  134. Annu Rev Pathol. 2009;4:365-98 - PubMed
  135. Nat Biotechnol. 2019 Aug;37(8):907-915 - PubMed
  136. iScience. 2021 Aug 20;24(8):102823 - PubMed
  137. Autoimmun Rev. 2020 Jul;19(7):102567 - PubMed
  138. Cell Discov. 2020 Nov 10;6(1):83 - PubMed
  139. Emerg Microbes Infect. 2020 Dec;9(1):761-770 - PubMed
  140. Cell. 2020 Nov 25;183(5):1340-1353.e16 - PubMed
  141. PLoS One. 2021 Aug 4;16(8):e0255335 - PubMed
  142. Nat Commun. 2021 Jun 9;12(1):3501 - PubMed
  143. Int J Clin Pract. 2014 Apr;68(4):520-8 - PubMed
  144. Cell Commun Signal. 2021 Jul 8;19(1):73 - PubMed
  145. Front Cardiovasc Med. 2021 Jan 15;7:623012 - PubMed
  146. Brief Bioinform. 2021 Mar 22;22(2):1279-1290 - PubMed
  147. Sci Rep. 2020 Mar 6;10(1):4271 - PubMed
  148. Front Pharmacol. 2021 Jul 16;12:624006 - PubMed
  149. Immunity. 2020 Dec 15;53(6):1296-1314.e9 - PubMed
  150. Proteomics. 2021 Jun;21(11-12):e2000278 - PubMed
  151. Front Immunol. 2021 Jun 28;12:686699 - PubMed
  152. Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3799-804 - PubMed
  153. Toxicol Appl Pharmacol. 2010 Jul;246(1-2):91-9 - PubMed
  154. Arthritis Rheum. 2000 Jan;43(1):38-47 - PubMed
  155. Cells. 2019 Oct 30;8(11): - PubMed
  156. Cell. 2021 Apr 1;184(7):1895-1913.e19 - PubMed
  157. J Virol. 2021 Jun 24;95(14):e0013021 - PubMed
  158. Viruses. 2021 May 28;13(6): - PubMed
  159. Front Immunol. 2021 Feb 16;12:581469 - PubMed
  160. J Biomol Struct Dyn. 2021 Jun;39(9):3194-3203 - PubMed
  161. Comput Biol Med. 2021 Jan;128:104123 - PubMed
  162. Comput Biol Med. 2021 Jan;128:104126 - PubMed
  163. Front Immunol. 2021 Jun 24;12:648250 - PubMed
  164. Front Immunol. 2020 Jul 10;11:1708 - PubMed
  165. Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3747-52 - PubMed
  166. Pain Rep. 2021 Jan 07;6(1):e885 - PubMed
  167. Environ Sci Pollut Res Int. 2021 Dec;28(46):65769-65775 - PubMed
  168. Nat Immunol. 2017 Apr 18;18(5):488-498 - PubMed
  169. Free Radic Biol Med. 2021 Aug 20;172:688-698 - PubMed
  170. Brief Bioinform. 2018 Jul 20;19(4):575-592 - PubMed
  171. BMC Genomics. 2009 Jul 20;10:327 - PubMed
  172. Chin J Nat Med. 2020 Dec;18(12):881-889 - PubMed
  173. Int J Mol Med. 2019 Sep;44(3):771-786 - PubMed
  174. Mol Immunol. 2020 Feb;118:73-78 - PubMed
  175. Cell Mol Immunol. 2020 Sep;17(9):998-1000 - PubMed
  176. J Exp Med. 2020 Dec 7;217(12): - PubMed
  177. Nat Rev Immunol. 2015 Jun;15(6):388-400 - PubMed
  178. Sci Rep. 2021 Mar 29;11(1):7052 - PubMed
  179. Biochem Biophys Res Commun. 2020 Jun 11;526(4):947-952 - PubMed
  180. Int J Surg. 2020 Apr;76:71-76 - PubMed
  181. Front Pharmacol. 2021 Jun 09;12:631206 - PubMed
  182. Nucleic Acids Res. 2019 Jan 8;47(D1):D33-D38 - PubMed
  183. BMC Res Notes. 2015 May 03;8:182 - PubMed
  184. Int Immunopharmacol. 2020 Nov;88:106995 - PubMed
  185. Chin Med. 2021 Mar 3;16(1):25 - PubMed
  186. Front Genet. 2021 Mar 08;12:627623 - PubMed
  187. J Leukoc Biol. 2021 May 31;: - PubMed
  188. Nat Immunol. 2021 Jan;22(1):32-40 - PubMed
  189. Brief Bioinform. 2021 May 20;22(3): - PubMed
  190. Front Physiol. 2021 Apr 27;12:652799 - PubMed
  191. Front Pharmacol. 2020 Jul 10;11:1095 - PubMed
  192. J Enzyme Inhib Med Chem. 2021 Dec;36(1):1258-1267 - PubMed
  193. J Transl Med. 2020 Dec 3;18(1):457 - PubMed
  194. Front Immunol. 2020 Oct 23;11:582102 - PubMed
  195. Cancers (Basel). 2020 Jul 06;12(7): - PubMed
  196. Neurologia (Engl Ed). 2021 Jul 16;: - PubMed
  197. J Med Virol. 2021 Jan;93(1):250-256 - PubMed
  198. J Thromb Thrombolysis. 2021 Feb;51(2):446-453 - PubMed
  199. Cells. 2020 Dec 13;9(12): - PubMed
  200. Int J Mol Sci. 2021 Jul 26;22(15): - PubMed
  201. Mol Neurobiol. 2021 May;58(5):1875-1893 - PubMed
  202. Cell. 2021 Jan 7;184(1):120-132.e14 - PubMed
  203. Front Genet. 2021 Jul 05;12:668448 - PubMed
  204. J Immunol. 2013 Apr 15;190(8):4274-82 - PubMed
  205. Cell. 2008 Mar 7;132(5):818-31 - PubMed
  206. Int J Mol Sci. 2021 Mar 20;22(6): - PubMed
  207. J Transl Med. 2021 Jan 7;19(1):32 - PubMed
  208. Proc Natl Acad Sci U S A. 2021 Feb 9;118(6): - PubMed
  209. JCI Insight. 2021 Jan 11;6(1): - PubMed
  210. J Mol Cell Biol. 2021 Mar 10;12(12):946-957 - PubMed
  211. Sci Transl Med. 2020 Dec 16;12(574): - PubMed
  212. Comput Struct Biotechnol J. 2020 Dec 17;19:153-160 - PubMed
  213. Medicine (Baltimore). 2018 Feb;97(5):e9687 - PubMed
  214. Science. 2020 Sep 4;369(6508): - PubMed
  215. Nat Commun. 2020 Jul 8;11(1):3410 - PubMed
  216. Crit Care Med. 2020 Jul;48(7):e599-e610 - PubMed
  217. Cell. 2021 Jan 7;184(1):92-105.e16 - PubMed
  218. J Infect Dis. 2020 Aug 17;222(6):894-898 - PubMed
  219. J Biol Regul Homeost Agents. 2020 Mar 14;34(2):327-331 - PubMed
  220. Blood. 2005 Oct 1;106(7):2366-74 - PubMed
  221. Nat Rev Immunol. 2020 Jun;20(6):355-362 - PubMed
  222. FEBS J. 2016 May;283(10):1812-22 - PubMed
  223. PLoS Pathog. 2021 Jun 28;17(6):e1009687 - PubMed
  224. Front Immunol. 2021 Feb 24;12:625881 - PubMed
  225. Front Immunol. 2020 Dec 10;11:598444 - PubMed
  226. Trends Endocrinol Metab. 2021 Nov;32(11):842-845 - PubMed
  227. Curr Opin Immunol. 2007 Jun;19(3):301-8 - PubMed
  228. Cytokine Growth Factor Rev. 2020 Jun;53:38-42 - PubMed
  229. BMC Med Genomics. 2021 Sep 17;14(1):226 - PubMed
  230. J Pers Med. 2021 Jul 20;11(7): - PubMed
  231. J Pathol Clin Res. 2021 Sep;7(5):446-458 - PubMed
  232. Signal Transduct Target Ther. 2020 Mar 27;5(1):33 - PubMed
  233. J Cell Physiol. 2021 Jul;236(7):5325-5338 - PubMed
  234. Phytother Res. 2020 Nov;34(11):2786-2789 - PubMed
  235. Front Genet. 2020 Oct 27;11:558557 - PubMed
  236. Front Nutr. 2020 Sep 02;7:143 - PubMed
  237. Brief Bioinform. 2021 Mar 22;22(2):1415-1429 - PubMed
  238. Sci Rep. 2021 Jun 4;11(1):11886 - PubMed
  239. iScience. 2021 Apr 23;24(4):102293 - PubMed
  240. Pathog Immun. 2020 Oct 22;5(1):291-311 - PubMed
  241. J Virol. 2006 Mar;80(6):2684-93 - PubMed
  242. Vaccines (Basel). 2020 Nov 12;8(4): - PubMed
  243. Cell Rep. 2020 Oct 6;33(1):108234 - PubMed
  244. Autophagy. 2020 Dec;16(12):2131-2139 - PubMed
  245. Arthritis Rheum. 1998 Jul;41(7):1258-65 - PubMed
  246. Front Genet. 2020 Jul 13;11:722 - PubMed
  247. Nat Struct Mol Biol. 2020 Oct;27(10):959-966 - PubMed
  248. J Microbiol Immunol Infect. 2020 Jun;53(3):368-370 - PubMed
  249. Cell Rep. 2021 May 4;35(5):109055 - PubMed
  250. Nat Rev Immunol. 2020 May;20(5):269-270 - PubMed
  251. Cell Death Differ. 2019 Jan;26(1):4-13 - PubMed
  252. Clin Rheumatol. 2020 Jul;39(7):2085-2094 - PubMed
  253. Aging Dis. 2021 Feb 1;12(1):42-49 - PubMed
  254. J Stat Softw. 2012 Mar;46(11): - PubMed
  255. Genome Biol. 2014 Feb 03;15(2):R29 - PubMed
  256. Rheumatol Int. 2015 Apr;35(4):727-34 - PubMed
  257. Brief Bioinform. 2021 Mar 22;22(2):1175-1196 - PubMed
  258. BMC Pharmacol Toxicol. 2020 Sep 3;21(1):65 - PubMed
  259. Nat Rev Immunol. 2002 Oct;2(10):735-47 - PubMed
  260. Cell. 2020 Dec 10;183(6):1479-1495.e20 - PubMed
  261. J Cell Mol Med. 2021 Jul;25(14):7001-7012 - PubMed
  262. BMC Genomics. 2020 Oct 2;21(1):684 - PubMed
  263. Cell Mol Immunol. 2020 May;17(5):533-535 - PubMed
  264. J Infect. 2021 Mar;82(3):e4-e7 - PubMed
  265. Autoimmun Rev. 2021 Oct;20(10):102909 - PubMed
  266. Ann Rheum Dis. 2002 Aug;61(8):723-5 - PubMed
  267. Clin Immunol. 2021 Jun;227:108723 - PubMed
  268. Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613 - PubMed
  269. Viruses. 2020 Jul 20;12(7): - PubMed
  270. PLoS One. 2014 Apr 17;9(4):e94868 - PubMed
  271. Viruses. 2021 Jan 08;13(1): - PubMed
  272. Nat Med. 2020 Jul;26(7):1070-1076 - PubMed
  273. EBioMedicine. 2021 May;67:103378 - PubMed
  274. Signal Transduct Target Ther. 2020 Dec 24;5(1):294 - PubMed
  275. Rheumatol Int. 2021 Jan;41(1):7-18 - PubMed
  276. Front Immunol. 2021 Jun 21;12:677008 - PubMed
  277. Immunol Lett. 2020 Sep;225:31-32 - PubMed
  278. Front Pharmacol. 2020 Oct 16;11:588508 - PubMed
  279. Cell. 2020 Aug 6;182(3):734-743.e5 - PubMed
  280. Eur J Med Res. 2021 Jul 13;26(1):75 - PubMed
  281. Inflammopharmacology. 2021 Feb;29(1):91-100 - PubMed
  282. Acta Biomed. 2020 Mar 19;91(1):157-160 - PubMed
  283. Immunity. 2021 Jun 8;54(6):1304-1319.e9 - PubMed
  284. Front Pharmacol. 2020 Sep 16;11:556984 - PubMed
  285. Int Immunopharmacol. 2021 Nov;100:108125 - PubMed
  286. Front Genet. 2021 Mar 16;12:599261 - PubMed
  287. Brain Behav Immun. 2020 Jul;87:59-73 - PubMed
  288. Front Immunol. 2020 May 01;11:827 - PubMed
  289. Int Immunopharmacol. 2020 Jul;84:106560 - PubMed
  290. Autoimmun Rev. 2020 Jul;19(7):102571 - PubMed
  291. J Inflamm (Lond). 2020 Oct 29;17:33 - PubMed
  292. Arthritis Rheum. 1996 Jul;39(7):1077-81 - PubMed
  293. Front Public Health. 2020 Jul 03;8:281 - PubMed
  294. Sci Rep. 2021 Jul 16;11(1):14601 - PubMed
  295. Lancet. 2020 Feb 15;395(10223):497-506 - PubMed
  296. Autoimmun Rev. 2020 Jun;19(6):102537 - PubMed
  297. J Clin Med. 2020 Apr 01;9(4): - PubMed
  298. Front Immunol. 2020 Jun 23;11:1512 - PubMed
  299. Int Immunopharmacol. 2021 Jun;95:107586 - PubMed
  300. NPJ Syst Biol Appl. 2021 May 24;7(1):21 - PubMed
  301. Int J Med Sci. 2020 Sep 12;17(16):2511-2530 - PubMed
  302. J Infect Dis. 2016 Mar 15;213(6):904-14 - PubMed
  303. Drug Deliv. 2021 Dec;28(1):325-342 - PubMed
  304. J Immunol. 2021 May 1;206(9):2146-2159 - PubMed
  305. Front Pharmacol. 2020 Oct 08;11:581277 - PubMed
  306. Sci Rep. 2020 Nov 10;10(1):19395 - PubMed
  307. PLoS Biol. 2020 Nov 6;18(11):e3000970 - PubMed
  308. Phytother Res. 2021 Jan 15;: - PubMed
  309. Pathologe. 2021 Nov;42(Suppl 1):89-97 - PubMed
  310. Commun Biol. 2021 May 17;4(1):590 - PubMed
  311. BMC Bioinformatics. 2008 Dec 29;9:559 - PubMed
  312. Eur J Immunol. 2020 Sep;50(9):1412-1414 - PubMed
  313. Immunology. 2021 Jan;162(1):30-43 - PubMed
  314. Cell. 2020 Sep 17;182(6):1419-1440.e23 - PubMed
  315. Gut. 1997 Apr;40(4):443-8 - PubMed
  316. Eur J Hum Genet. 2021 Aug;29(8):1312-1315 - PubMed
  317. Nature. 2015 Oct 29;526(7575):660-5 - PubMed
  318. Medicine (Baltimore). 2021 Jan 8;100(1):e23582 - PubMed
  319. Cell Discov. 2021 Jun 8;7(1):42 - PubMed
  320. Eur J Immunol. 2010 Jul;40(7):1830-5 - PubMed
  321. Front Immunol. 2021 Jun 25;12:653110 - PubMed
  322. J Med Virol. 2021 Sep;93(9):5544-5554 - PubMed
  323. Nat Biotechnol. 2020 Aug;38(8):970-979 - PubMed
  324. Cytokine. 2009 Sep;47(3):149-56 - PubMed
  325. J Ethnopharmacol. 2021 Jun 12;273:113871 - PubMed
  326. J Clin Med. 2020 Nov 21;9(11): - PubMed
  327. Mitochondrion. 2020 Sep;54:1-7 - PubMed
  328. Cell. 2020 May 28;181(5):1036-1045.e9 - PubMed
  329. F1000Res. 2020 Jun 15;9:609 - PubMed
  330. Nat Methods. 2012 Nov;9(11):1069-76 - PubMed
  331. Biochem Biophys Res Commun. 2021 Jan 15;536:59-66 - PubMed
  332. Front Cardiovasc Med. 2020 Nov 03;7:582399 - PubMed
  333. Front Immunol. 2020 Jun 23;11:1518 - PubMed
  334. Cell Discov. 2020 May 4;6:31 - PubMed
  335. Front Physiol. 2019 Aug 20;10:1081 - PubMed
  336. Signal Transduct Target Ther. 2020 Aug 14;5(1):156 - PubMed
  337. Signal Transduct Target Ther. 2021 Mar 6;6(1):110 - PubMed
  338. Int J Mol Sci. 2021 Jul 01;22(13): - PubMed
  339. Clin Chim Acta. 2020 Sep;508:254-266 - PubMed
  340. Biol Sex Differ. 2020 May 25;11(1):29 - PubMed
  341. Signal Transduct Target Ther. 2020 Oct 9;5(1):235 - PubMed
  342. iScience. 2020 Oct 23;23(10):101611 - PubMed
  343. J Infect Dis. 2020 Feb 3;221(4):647-659 - PubMed
  344. Science. 2020 Sep 4;369(6508):1210-1220 - PubMed
  345. Int J Infect Dis. 2021 Apr;105:49-53 - PubMed
  346. J Clin Med. 2021 Apr 09;10(8): - PubMed
  347. Cells. 2021 Aug 07;10(8): - PubMed
  348. FASEB J. 2020 Jul;34(7):8787-8795 - PubMed
  349. Immunity. 2018 Feb 20;48(2):202-213 - PubMed
  350. Antioxid Redox Signal. 2014 Mar 1;20(7):1126-67 - PubMed
  351. EBioMedicine. 2020 Aug;58:102925 - PubMed
  352. Lancet. 2020 Feb 15;395(10223):507-513 - PubMed
  353. Biomed Pharmacother. 2021 Jun;138:111437 - PubMed
  354. Clin Transl Med. 2020 Oct;10(6):e200 - PubMed
  355. Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28336-28343 - PubMed
  356. J Exp Med. 2020 Jun 1;217(6): - PubMed
  357. Sci Rep. 2021 Jul 8;11(1):14151 - PubMed
  358. Antiviral Res. 2020 Jun;178:104791 - PubMed
  359. Nat Cell Biol. 2021 May;23(5):538-551 - PubMed
  360. Front Immunol. 2021 Apr 14;12:651656 - PubMed
  361. iScience. 2020 Sep 25;23(9):101526 - PubMed
  362. Cell. 2021 Jan 7;184(1):149-168.e17 - PubMed
  363. Proteomics. 2021 Aug;21(15):e2100002 - PubMed
  364. Eur J Immunol. 2021 Aug 1;: - PubMed
  365. Am J Physiol Cell Physiol. 2020 Aug 1;319(2):C258-C267 - PubMed
  366. Sci Rep. 2016 Jan 04;6:18424 - PubMed
  367. Cell Host Microbe. 2020 Jun 10;27(6):879-882.e2 - PubMed
  368. Nat Rev Immunol. 2020 Jun;20(6):363-374 - PubMed
  369. Med Hypotheses. 2020 Nov;144:110161 - PubMed
  370. Biomed Pharmacother. 2020 Aug;128:110316 - PubMed
  371. Int J Mol Sci. 2021 Sep 22;22(19): - PubMed
  372. J Med Virol. 2021 Feb;93(2):1105-1110 - PubMed
  373. Signal Transduct Target Ther. 2017;2: - PubMed
  374. Br J Pharmacol. 2020 Nov;177(21):4899-4920 - PubMed
  375. Eur J Pharmacol. 2021 Apr 15;897:173928 - PubMed
  376. Scand J Immunol. 2019 Jul;90(1):e12771 - PubMed
  377. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8685-90 - PubMed
  378. Front Immunol. 2014 Apr 16;5:167 - PubMed
  379. J Med Virol. 2021 Mar;93(3):1589-1598 - PubMed
  380. Curr Opin Immunol. 2018 Dec;55:9-14 - PubMed
  381. Int J Mol Sci. 2021 Mar 15;22(6): - PubMed
  382. Nat Microbiol. 2021 Mar;6(3):339-353 - PubMed
  383. Placenta. 2021 Jan 1;103:141-151 - PubMed
  384. Infect Agent Cancer. 2021 Mar 16;16(1):18 - PubMed
  385. Front Immunol. 2020 Dec 03;11:611004 - PubMed
  386. Nat Med. 2020 Oct;26(10):1636-1643 - PubMed
  387. Front Pharmacol. 2020 Nov 19;11:569849 - PubMed
  388. Cell Metab. 2021 Aug 3;33(8):1565-1576.e5 - PubMed
  389. Science. 2020 Aug 7;369(6504):718-724 - PubMed
  390. Front Immunol. 2021 Jun 28;12:595150 - PubMed
  391. Saudi J Biol Sci. 2021 Dec;28(12):6939-6945 - PubMed
  392. Immun Inflamm Dis. 2020 Dec;8(4):753-762 - PubMed
  393. Am J Hum Genet. 2007 Jun;80(6):1103-14 - PubMed
  394. iScience. 2021 Mar 19;24(3):102151 - PubMed
  395. Cell Discov. 2020 Oct 20;6:73 - PubMed
  396. Eur J Pharmacol. 2020 Nov 15;887:173594 - PubMed
  397. Mol Cell Endocrinol. 2020 Sep 15;515:110917 - PubMed
  398. JCI Insight. 2020 Jul 9;5(13): - PubMed
  399. Lancet Rheumatol. 2020 Nov;2(11):e653-e655 - PubMed
  400. Environ Int. 2021 Dec;157:106232 - PubMed
  401. Circ Res. 2021 Sep 3;129(6):631-646 - PubMed
  402. Nat Immunol. 2020 Sep;21(9):1107-1118 - PubMed
  403. J Clin Med. 2019 Aug 02;8(8): - PubMed
  404. Sci Rep. 2020 Nov 30;10(1):20836 - PubMed
  405. Int J Mol Sci. 2021 Aug 05;22(16): - PubMed
  406. Nat Rev Immunol. 2006 Dec;6(12):940-52 - PubMed
  407. Science. 2020 Sep 4;369(6508):1249-1255 - PubMed
  408. Sci Transl Med. 2021 Sep 22;13(612):eabh2624 - PubMed
  409. Sci Rep. 2020 Nov 30;10(1):20848 - PubMed
  410. Cell Discov. 2020 Sep 15;6:65 - PubMed
  411. Cell Syst. 2021 Jan 20;12(1):23-40.e7 - PubMed
  412. Microbiol Immunol. 2021 Oct;65(10):422-431 - PubMed
  413. Front Pharmacol. 2020 Dec 15;11:615972 - PubMed
  414. Antioxidants (Basel). 2021 Sep 09;10(9): - PubMed
  415. Int Immunopharmacol. 2021 Nov;100:108071 - PubMed
  416. Nat Biotechnol. 2021 Sep 6;: - PubMed
  417. mSphere. 2020 Jun 24;5(3): - PubMed

Publication Types