Generating synthetic signaling networks for in silico modeling studies.

Jin Xu, H Steven Wiley, Herbert M Sauro
Author Information
  1. Jin Xu: Department of Bioengineering, University of Washington, Seattle 98195, WA, USA. Electronic address: jxu2019@uw.edu.
  2. H Steven Wiley: Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland 99352, WA, USA.
  3. Herbert M Sauro: Department of Bioengineering, University of Washington, Seattle 98195, WA, USA.

Abstract

Predictive models of signaling pathways have proven to be difficult to develop. Traditional approaches to developing mechanistic models rely on collecting experimental data and fitting a single model to that data. This approach works for simple systems but has proven unreliable for complex systems such as biological signaling networks. Thus, there is a need to develop new approaches to create predictive mechanistic models of complex systems. To meet this need, we developed a method for generating artificial signaling networks that were reasonably realistic and thus could be treated as ground truth models. These synthetic models could then be used to generate synthetic data for developing and testing algorithms designed to recover the underlying network topology and associated parameters. We defined the reaction degree and reaction distance to measure the topology of reaction networks, especially to consider enzymes. To determine whether our generated signaling networks displayed meaningful behavior, we compared them with signaling networks from the BioModels Database. This comparison indicated that our generated signaling networks had high topological similarities with BioModels signaling networks with respect to the reaction degree and distance distributions. In addition, our synthetic signaling networks had similar behavioral dynamics with respect to both steady states and oscillations, suggesting that our method generated synthetic signaling networks comparable with BioModels and thus could be useful for building network evaluation tools.

Keywords

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Grants

  1. U01 CA227544/NCI NIH HHS
  2. R01 GM123032/NIGMS NIH HHS

MeSH Term

Signal Transduction
Models, Biological
Computer Simulation
Algorithms
Synthetic Biology

Word Cloud

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