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Formal Modeling and Analysis of Pancreatic Cancer Microenvironment

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Computational Methods in Systems Biology (CMSB 2016)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 9859))

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Abstract

The focus of pancreatic cancer research has been shifted from pancreatic cancer cells towards their microenvironment, involving pancreatic stellate cells that interact with cancer cells and influence tumor progression. To quantitatively understand the pancreatic cancer microenvironment, we construct a computational model for intracellular signaling networks of cancer cells and stellate cells as well as their intercellular communication. We extend the rule-based BioNetGen language to depict intra- and inter-cellular dynamics using discrete and continuous variables respectively. Our framework also enables a statistical model checking procedure for analyzing the system behavior in response to various perturbations. The results demonstrate the predictive power of our model by identifying important system properties that are consistent with existing experimental observations. We also obtain interesting insights into the development of novel therapeutic strategies for pancreatic cancer.

This work was partially supported by ONR Award (N00014-13-1-0090), NSF CPS Breakthrough (CNS-1330014), NSF CPS Frontier (CNS-1446725), and NIH award U54HG008540.

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Author information

Authors and Affiliations

  1. Computer Science Department, Carnegie Mellon University, Pittsburgh, USA

    Qinsi Wang & Edmund M. Clarke

  2. Electrical and Computer Engineering Department, Carnegie Mellon University, Pittsburgh, USA

    Natasa Miskov-Zivanov

  3. Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, USA

    Bing Liu & James R. Faeder

  4. Surgery and Bioengineering, UPMC, Pittsburgh, USA

    Michael Lotze

Authors
  1. Qinsi Wang
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  2. Natasa Miskov-Zivanov
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  3. Bing Liu
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  4. James R. Faeder
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  5. Michael Lotze
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  6. Edmund M. Clarke
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Corresponding author

Correspondence to Qinsi Wang .

Editor information

Editors and Affiliations

  1. TU Wien, Vienna, Austria

    Ezio Bartocci

  2. Computer Laboratory, University of Cambridge, Cambridge, United Kingdom

    Pietro Lio

  3. Department of Computer Science, University of Oxford, Oxford, United Kingdom

    Nicola Paoletti

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Wang, Q., Miskov-Zivanov, N., Liu, B., Faeder, J.R., Lotze, M., Clarke, E.M. (2016). Formal Modeling and Analysis of Pancreatic Cancer Microenvironment. In: Bartocci, E., Lio, P., Paoletti, N. (eds) Computational Methods in Systems Biology. CMSB 2016. Lecture Notes in Computer Science(), vol 9859. Springer, Cham. https://doi.org/10.1007/978-3-319-45177-0_18

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  • DOI: https://doi.org/10.1007/978-3-319-45177-0_18

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  • Publisher Name: Springer, Cham

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  • Online ISBN: 978-3-319-45177-0

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