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Formal Modeling of the Key Determinants of Hepatitis C Virus (HCV) Induced Adaptive Immune Response Network: An Integrative Approach to Map the Cellular and Cytokine-Mediated Host Immune Regulations

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Computational Science and Its Applications – ICCSA 2018 (ICCSA 2018)

Part of the book series: Lecture Notes in Computer Science ((LNTCS,volume 10963))

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Abstract

HCV is a major causative agent of liver infection and is the leading cause of Hepatocellular carcinoma (HCC). To understand the complexity in interactions within the HCV induced immune signaling networks, a logic-based diagram is generated based on multiple reported interactions. A simple conceptual framework is presented to explore the key determinants of the immune system and their functions during HCV infection. Furthermore, an abstracted sub-network is modeled qualitatively which consists of both the key cellular and cytokine components of the HCV induced immune system. In the presence of NS5A protein of HCV, the behaviors and the interplay amongst the natural killer (NK) and T regulatory (Tregs) cells along with cytokines such as IFN-γ, IL-10, IL-12 are predicted. The overall modelling approach followed in this study comprises of prior knowledge-based logical interaction network, network abstraction, parameter estimation, regulatory network construction and analysis through state graph, enabling the prediction of paths leading to both, disease state and a homeostatic path/cycle predicted based on maximum betweenness centrality. To study the continuous dynamics of the network, Petri net (PN) model was generated. The analysis implicates the critical role of IFN-γ producing NK cells in recovery while, the role of IL-10 and IL-12 in pathogenesis. The predictive ability of the model implicates that IL-12 has a dual role under varying circumstances and leads to varying disease outcomes. This model attempts to reduce the noisy biological data and captures a holistic view of the key determinants of the HCV induced immune response.

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Acknowledgement

This research is supported by Higher Education Commission (HEC) of Pakistan, NRPU grant no. 4362.

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Authors and Affiliations

  1. Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 44,000, Pakistan

    Ayesha Obaid, Anam Naz, Shifa Tariq Ashraf, Faryal Mehwish Awan, Aqsa Ikram & Amjad Ali

  2. Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, Pakistan

    Muhammad Tariq Saeed & Jamil Ahmad

  3. National Institute of Lasers and Optronics (NILOP), Islamabad, Pakistan

    Abida Raza

Authors
  1. Ayesha Obaid
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  2. Anam Naz
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  3. Shifa Tariq Ashraf
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  4. Faryal Mehwish Awan
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  5. Aqsa Ikram
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  6. Muhammad Tariq Saeed
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  7. Abida Raza
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  8. Jamil Ahmad
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  9. Amjad Ali
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Correspondence to Amjad Ali .

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Editors and Affiliations

  1. University of Perugia, Perugia, Italy

    Osvaldo Gervasi

  2. University of Basilicata, Potenza, Italy

    Beniamino Murgante

  3. Covenant University, Ota, Nigeria

    Sanjay Misra

  4. Saint Petersburg State University, Saint Petersburg, Russia

    Elena Stankova

  5. Polytechnic University of Bari, Bari, Italy

    Carmelo M. Torre

  6. University of Minho, Braga, Portugal

    Ana Maria A.C. Rocha

  7. Monash University, Clayton, Victoria, Australia

    David Taniar

  8. Kyushu Sangyo University, Fukuoka shi, Fukuoka, Japan

    Bernady O. Apduhan

  9. Politecnico di Bari, Bari, Italy

    Eufemia Tarantino

  10. Myongji University, Yongin, Korea (Republic of)

    Yeonseung Ryu

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Obaid, A. et al. (2018). Formal Modeling of the Key Determinants of Hepatitis C Virus (HCV) Induced Adaptive Immune Response Network: An Integrative Approach to Map the Cellular and Cytokine-Mediated Host Immune Regulations. In: Gervasi, O., et al. Computational Science and Its Applications – ICCSA 2018. ICCSA 2018. Lecture Notes in Computer Science(), vol 10963. Springer, Cham. https://doi.org/10.1007/978-3-319-95171-3_50

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  • DOI: https://doi.org/10.1007/978-3-319-95171-3_50

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-95170-6

  • Online ISBN: 978-3-319-95171-3

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