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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Aslam, Babar Ahmad, Jamil Ali, Amjad Zafar Paracha, Rehan Tareen, Samar Hayat Khan Niazi, Umar Saeed, Tariq |
| Description | Country affiliation: Pakistan Author Affiliation: Aslam B ( Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.); Ahmad J ( Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan. Electronic address: jamil.ahmad@rcms.nust.edu.pk.); Ali A ( Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.); Zafar Paracha R ( Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.); Tareen SH ( Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.); Niazi U ( IBERS, Aberystwyth University, Edward Llwyd Building, Penglais Campus, Aberystwyth, Ceredigion, Wales SY23 3FG, UK.); Saeed T ( Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.) |
| Abstract | Dengue virus can ignite both protective and pathogenic responses in human. The pathogenesis is related with modified functioning of our immune system during infection. Pattern recognition receptors like Toll like receptor 3 is vital for the induction of innate immunity in case of Dengue infection. Toll like receptor 3 induces TRIF mediated activation of Type 1 interferons and Fc receptor mediated induction of cytokines. Interferons have been related with clearance of Dengue virus but it has adopted modified regulatory mechanisms to counter this effect. SOCS protein is also induced due to the interferon and cytokine mediated signalling which can subsequently play its part in the regulation of interferon and cytokine production. Our hypothesis in this study relates the pathogenesis of Dengue virus with the SOCS mediated inhibition of our innate immunity. We used the qualitative formalism of René Thomas to model the biological regulatory network of Toll like receptor 3 mediated signalling pathway in an association with pathogenesis of dengue. Logical parameters for the qualitative modelling were inferred using a model checking approach implemented in SMBioNet. A linear hybrid model, parametric linear hybrid automaton, was constructed to incorporate the activation and inhibition time delays in the qualitative model. The qualitative model captured all the possible expression dynamics of the proteins in the form of paths, some of which were observed as abstract cycles (representing homoeostasis) and diverging paths towards stable states. The analysis of the qualitative model highlighted the importance of SOCS protein in elevating propagation of dengue virus through inhibition of type 1 interferons. Detailed qualitative analysis of regulatory network endorses our hypothesis that elevated levels of cytokine subsequently induce SOCS expression which in turn results into the continuous down-regulation of Toll like receptor 3 and interferon. This may result into the Dengue pathogenesis during the stage of immunosuppression. Further analysis with HyTech (HYbrid TECHnology) tool provided us with the real-time constraints (delay constraints) of the proteins involved in the cyclic paths of the regulatory network backing the evidence provided by the qualitative analysis. The HyTech results also suggest that the role of SOCS is vital in homoeostasis. |
| File Format | HTM / HTML |
| ISSN | 14769271 |
| Journal | Computational Biology and Chemistry |
| Volume Number | 53PB |
| e-ISSN | 1476928X |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2014-10-14 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Medical Informatics Discipline Chemistry Discipline Computational Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Organic Chemistry Structural Biology Biochemistry Computational Mathematics |
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