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Construction of Cell Type-Specific Logic Models of Signaling Networks Using CellNOpt

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Computational Toxicology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 930))

Abstract

Mathematical models are useful tools for understanding protein signaling networks because they provide an integrated view of pharmacological and toxicological processes at the molecular level. Here we describe an approach previously introduced based on logic modeling to generate cell-specific, mechanistic and predictive models of signal transduction. Models are derived from a network encoding prior knowledge that is trained to signaling data, and can be either binary (based on Boolean logic) or quantitative (using a recently developed formalism, constrained fuzzy logic). The approach is implemented in the freely available tool CellNetOptimizer (CellNOpt). We explain the process CellNOpt uses to train a prior knowledge network to data and illustrate its application with a toy example as well as a realistic case describing signaling networks in the HepG2 liver cancer cell line.

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Acknowledgments

We thank Peter K. Sorger and Douglas A. Lauffenburger for guidance during the development of CellNOpt. The original development of CellNOpt was funded by NIH grants P50-GM68762 and U54-CA112967 and the DoD Institute for Collaborative Biotechnologies (http://www.icb.ucsb.edu/). We also thank Beatriz Penalver, Leonidas G. Alexopoulos, Regina Samaga, Jonathan Epperlein, Steffen Klamt for their contributions to CellNOpt, and to Camille Terfve, David Henriques, Aidan MacNamara, and Francesco Iorio for critically reading the manuscript.

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Authors and Affiliations

  1. Center for Cell Decision Processes Massachusetts Institute of Technology and Harvard Medical School, Cambridge, MA, USA

    Melody K. Morris

  2. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Melody K. Morris

  3. European Bioinformatics Institute (EMBL-EBI), Cambridge, UK

    Ioannis Melas & Julio Saez-Rodriguez

  4. National Technical University of Athens, Athens, Greece

    Ioannis Melas

  5. Genome Biology Unit, European Molecular Biology Laboratory(EMBL), Heidelberg, Germany

    Julio Saez-Rodriguez

Authors
  1. Melody K. Morris
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  2. Ioannis Melas
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  3. Julio Saez-Rodriguez
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Correspondence to Julio Saez-Rodriguez .

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Editors and Affiliations

  1. School of Biomedical Engineering, Chemical & Biological Engineering, Colorado State University, Campus Delivery 1370, Fort Collins, 80523-1370, Colorado, USA

    Brad Reisfeld

  2. , Chemical & Biological Engineering, Colorado State University, Campus Delivery 1370, Fort Collins, 80523-1370, Colorado, USA

    Arthur N. Mayeno

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Morris, M.K., Melas, I., Saez-Rodriguez, J. (2013). Construction of Cell Type-Specific Logic Models of Signaling Networks Using CellNOpt . In: Reisfeld, B., Mayeno, A. (eds) Computational Toxicology. Methods in Molecular Biology, vol 930. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-059-5_8

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  • DOI: https://doi.org/10.1007/978-1-62703-059-5_8

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-058-8

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