{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T15:54:28Z","timestamp":1777996468378,"version":"3.51.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Whenever some phenomenon can be represented as a graph or a network it seems pertinent to explore how much the mathematical properties of that network impact the phenomenon. In this study we explore the same philosophy in the context of immunology. Our objective was to assess the correlation of \u201csize\u201d (number of edges and minimum vertex cover) of the JAK\/STAT network with treatment effect in rheumatoid arthritis (RA), phenotype of viral infection and effect of immunosuppressive agents on a system infected with the coronavirus. We extracted the JAK\/STAT pathway from Kyoto Encyclopedia of Genes and Genomes (KEGG, hsa04630). The effects of the following drugs, and their combinations, commonly used in RA were tested: methotrexate, prednisolone, rituximab, tocilizumab, tofacitinib and baricitinib. Following viral systems were also tested for their ability to evade the JAK\/STAT pathway: Measles, Influenza A, West Nile virus, Japanese B virus, Yellow Fever virus, respiratory syncytial virus, Kaposi\u2019s sarcoma virus, Hepatitis B and C virus, cytomegalovirus, Hendra and Nipah virus and Coronavirus. Good correlation of edges and minimum vertex cover with clinical efficacy were observed (for edge, rho\u2009=\u2009\u2009\u2212\u20090.815, R\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.676, p\u2009=\u20090.007, for vertex cover rho\u2009=\u2009\u2009\u2212\u20090.793, R\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.635, p\u2009=\u20090.011). In the viral systems both edges and vertex cover were associated with acuteness of viral infections. In the JAK\/STAT system already infected with coronavirus, maximum reduction in size was achieved with baricitinib. To conclude, algebraic and combinatorial invariant of a network may explain its biological behaviour. At least theoretically, baricitinib may be an attractive target for treatment of coronavirus infection.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-82139-x","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T06:04:39Z","timestamp":1611813879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Network theoretic analysis of JAK\/STAT pathway and extrapolation to drugs and viruses including COVID-19"],"prefix":"10.1038","volume":"11","author":[{"given":"Arindam","family":"Banerjee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudra Prosad","family":"Goswami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moumita","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"82139_CR1","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/B978-0-12-813651-5.00008-5","volume-title":"Mathematical Physics in Theoretical Chemistry","author":"KJ Burch","year":"2019","unstructured":"Burch, K. J. Chapter 8\u2014Chemical applications of graph theory. In Mathematical Physics in Theoretical Chemistry (eds Blinder, S. M. & House, J. E.) 261\u2013294 (Elsevier, Amsterdam, 2019) https:\/\/doi.org\/10.1016\/B978-0-12-813651-5.00008-5."},{"key":"82139_CR2","doi-asserted-by":"publisher","unstructured":"Herzog, J. & Hibi, T. Monomial Ideals. (eds. Herzog, J. & Hibi, T.) 3\u201322 (Springer, Berlin, 2011) https:\/\/doi.org\/10.1007\/978-0-85729-106-6_1.","DOI":"10.1007\/978-0-85729-106-6_1"},{"key":"82139_CR3","doi-asserted-by":"publisher","first-page":"9209","DOI":"10.1073\/pnas.1201416109","volume":"109","author":"D Breitkreutz","year":"2012","unstructured":"Breitkreutz, D., Hlatky, L., Rietman, E. & Tuszynski, J. A. Molecular signaling network complexity is correlated with cancer patient survivability. Proc. Natl. Acad. Sci. USA. 109, 9209\u20139212 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"82139_CR4","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1136\/annrheumdis-2019-216656","volume":"79","author":"A Kerschbaumer","year":"2020","unstructured":"Kerschbaumer, A. et al. Efficacy of pharmacological treatment in rheumatoid arthritis: A systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis. Ann. Rheum. Dis. 79, 744\u2013759. https:\/\/doi.org\/10.1136\/annrheumdis-2019-216656 (2020).","journal-title":"Ann. Rheum. Dis."},{"key":"82139_CR5","doi-asserted-by":"publisher","first-page":"108393","DOI":"10.1016\/j.clim.2020.108393","volume":"214","author":"W Zhang","year":"2020","unstructured":"Zhang, W. et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The perspectives of clinical immunologists from China. Clin. Immunol. 214, 108393 (2020).","journal-title":"Clin. Immunol."},{"key":"82139_CR6","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","volume":"395","author":"P Mehta","year":"2020","unstructured":"Mehta, P. et al. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 395, 1033\u20131034 (2020).","journal-title":"Lancet"},{"key":"82139_CR7","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa587","author":"JL Rodriguez-Garcia","year":"2020","unstructured":"Rodriguez-Garcia, J. L. et al. Baricitinib improves respiratory function in patients treated with corticosteroids for SARS-CoV-2 pneumonia: An observational cohort study. Rheumatology https:\/\/doi.org\/10.1093\/rheumatology\/keaa587 (2020).","journal-title":"Rheumatology"},{"key":"82139_CR8","doi-asserted-by":"publisher","first-page":"141772","DOI":"10.1172\/JCI141772","volume":"18","author":"V Bronte","year":"2020","unstructured":"Bronte, V. et al. Baricitinib restrains the immune dysregulation in severe COVID-19 patients. J. Clin. Investig. 18, 141772. https:\/\/doi.org\/10.1172\/JCI141772 (2020).","journal-title":"J. Clin. Investig."},{"key":"82139_CR9","unstructured":"KEGG: Kyoto Encyclopedia of Genes and Genomes. https:\/\/www.genome.jp\/kegg\/."},{"key":"82139_CR10","unstructured":"Zhang, J. D.\u00a0KEGGgraph: Application Examples. R package version 1.50.0. (2020)."},{"key":"82139_CR11","doi-asserted-by":"publisher","first-page":"D355","DOI":"10.1093\/nar\/gkp896","volume":"38","author":"M Kanehisa","year":"2010","unstructured":"Kanehisa, M., Goto, S., Furumichi, M., Tanabe, M. & Hirakawa, M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 38, D355-360 (2010).","journal-title":"Nucleic Acids Res."},{"key":"82139_CR12","doi-asserted-by":"publisher","first-page":"D277","DOI":"10.1093\/nar\/gkh063","volume":"32","author":"M Kanehisa","year":"2004","unstructured":"Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y. & Hattori, M. The KEGG resource for deciphering the genome. Nucleic Acids Res. 32, D277-280 (2004).","journal-title":"Nucleic Acids Res."},{"key":"82139_CR13","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1196\/annals.1310.009","volume":"1020","author":"CF Schaefer","year":"2004","unstructured":"Schaefer, C. F. Pathway Databases. Ann. N. Y. Acad. Sci. 1020, 77\u201391 (2004).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"82139_CR14","unstructured":"R Core Team. 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PLoS ONE 10, e0130078 (2015).","journal-title":"PLoS ONE"},{"key":"82139_CR17","doi-asserted-by":"publisher","first-page":"i17","DOI":"10.1093\/rheumatology\/key225","volume":"58","author":"PC Taylor","year":"2019","unstructured":"Taylor, P. C. Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis. Rheumatology 58, i17\u2013i26 (2019).","journal-title":"Rheumatology"},{"key":"82139_CR18","doi-asserted-by":"publisher","first-page":"3086","DOI":"10.3389\/fimmu.2018.03086","volume":"9","author":"HS Chiang","year":"2018","unstructured":"Chiang, H. S. & Liu, H. M. The molecular basis of viral inhibition of IRF- and STAT-dependent immune responses. Front. Immunol. 9, 3086 (2018).","journal-title":"Front. Immunol."},{"key":"82139_CR19","doi-asserted-by":"publisher","first-page":"e000889","DOI":"10.1136\/rmdopen-2018-000889","volume":"5","author":"F Buttgereit","year":"2019","unstructured":"Buttgereit, F. et al. Fosdagrocorat (PF-04171327) versus prednisone or placebo in rheumatoid arthritis: A randomised, double-blind, multicentre, phase IIb study. RMD Open 5, e000889 (2019).","journal-title":"RMD Open"},{"key":"82139_CR20","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1136\/ard.2009.119933","volume":"69","author":"P Emery","year":"2010","unstructured":"Emery, P. et al. Efficacy and safety of different doses and retreatment of rituximab: A randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab\u2019s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann. Rheum. Dis. 69, 1629\u20131635 (2010).","journal-title":"Ann. Rheum. Dis."},{"key":"82139_CR21","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1056\/NEJMoa1109071","volume":"367","author":"R Fleischmann","year":"2012","unstructured":"Fleischmann, R. et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N. Engl. J. Med. 367, 495\u2013507 (2012).","journal-title":"N. Engl. J. Med."},{"key":"82139_CR22","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1002\/art.39953","volume":"69","author":"R Fleischmann","year":"2017","unstructured":"Fleischmann, R. et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol. 69, 506\u2013517 (2017).","journal-title":"Arthritis Rheumatol."},{"key":"82139_CR23","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.1056\/NEJMoa032534","volume":"350","author":"JCW Edwards","year":"2004","unstructured":"Edwards, J. C. W. et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350, 2572\u20132581 (2004).","journal-title":"N. Engl. J. 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Arthritis Rheum. 38, 727\u2013735 (1995).","journal-title":"Arthritis Rheum."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82139-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82139-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82139-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T21:44:05Z","timestamp":1670017445000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82139-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,28]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["82139"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-82139-x","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-25845\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,28]]},"assertion":[{"value":"16 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2512"}}