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.
Highlights
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
Our objectives were to assess the correlation of “size” of the JAK/STAT network with treatment effect in rheumatoid arthritis (RA), phenotype of viral infections and effect of immunosuppressive agents on a system infected with the coronavirus
In the JAK/STAT system already infected with coronavirus the effect of adding the following drugs were tested: prednisolone, baricitinib and tocilizumab (Fig. 2 for edge and Fig. 3 for minimum vertex cover)
Summary
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. It turns out that for our case the number of edges is a good quantitative measure of effectiveness and minimum size of a vertex cover is a good qualitative measure. Biochemical networks, such as signalling pathways, like the JAK/STAT pathway, are protein–protein interaction networks. As in case of the effect of drugs, ability of these viruses to reduce the network size could be paralleled by their ability to successfully evade the host defence mechanisms for prolonged periods of time and result in chronicity. Our objectives were to assess the correlation of “size” of the JAK/STAT network with treatment effect in rheumatoid arthritis (RA), phenotype of viral infections and effect of immunosuppressive agents on a system infected with the coronavirus
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
