Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19

Abstract 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 correlatio...

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Autores principales:	Arindam Banerjee, Rudra Prosad Goswami, Moumita Chatterjee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/554ef04ec0e4423590e724823127b30b
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spelling	oai:doaj.org-article:554ef04ec0e4423590e724823127b30b2021-12-02T10:47:54ZNetwork theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-1910.1038/s41598-021-82139-x2045-2322https://doaj.org/article/554ef04ec0e4423590e724823127b30b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82139-xhttps://doaj.org/toc/2045-2322Abstract 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 “size” (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’s 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 = − 0.815, R2 = 0.676, p = 0.007, for vertex cover rho = − 0.793, R2 = 0.635, p = 0.011). 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.Arindam BanerjeeRudra Prosad GoswamiMoumita ChatterjeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arindam Banerjee Rudra Prosad Goswami Moumita Chatterjee Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19
description	Abstract 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 “size” (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’s 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 = − 0.815, R2 = 0.676, p = 0.007, for vertex cover rho = − 0.793, R2 = 0.635, p = 0.011). 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.
format	article
author	Arindam Banerjee Rudra Prosad Goswami Moumita Chatterjee
author_facet	Arindam Banerjee Rudra Prosad Goswami Moumita Chatterjee
author_sort	Arindam Banerjee
title	Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19
title_short	Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19
title_full	Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19
title_fullStr	Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19
title_full_unstemmed	Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19
title_sort	network theoretic analysis of jak/stat pathway and extrapolation to drugs and viruses including covid-19
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/554ef04ec0e4423590e724823127b30b
work_keys_str_mv	AT arindambanerjee networktheoreticanalysisofjakstatpathwayandextrapolationtodrugsandvirusesincludingcovid19 AT rudraprosadgoswami networktheoreticanalysisofjakstatpathwayandextrapolationtodrugsandvirusesincludingcovid19 AT moumitachatterjee networktheoreticanalysisofjakstatpathwayandextrapolationtodrugsandvirusesincludingcovid19
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Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19

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