In silico investigation of novel biological pathways: The role of CD200 in regulation of T cell priming in experimental autoimmune encephalomyelitis

Richard B. Greaves*, Mark Read, Jon Timmis, Paul S. Andrews, James A. Butler, Bjorn Ole Gerckens, Vipin Kumar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (SciVal)

Abstract

The use of simulation to investigate biological domains will inevitably lead to the need to extend existing simulations as new areas of these domains become more fully understood. Such simulation extensions can entail the incorporation of additional cell types, molecules or molecular pathways, all of which can exert a profound influence on the simulation behaviour. Where the biological domain is not well characterised, a structured development methodology must be employed to ensure that the extended simulation is well aligned with its predecessor. We develop and discuss such a methodology, relying on iterative simulation development and sensitivity analysis. The utility of this methodology is demonstrated using a case study simulation of experimental autoimmune encephalomyelitis (EAE), a murine T cell-mediated autoimmune disease model of multiple sclerosis, where it is used to investigate the activity of an additional regulatory pathway. We discuss how application of this methodology guards against creating inappropriate simulation representations of the biology when investigating poorly characterised biological mechanisms.

Original languageEnglish
Pages (from-to)107-121
Number of pages15
JournalBioSystems
Volume112
Issue number2
DOIs
Publication statusPublished - May 2013
Externally publishedYes

Keywords

  • Agent-based simulation
  • CD200
  • Experimental autoimmune encephalomyelitis
  • In silico experimentation
  • Principled simulation development
  • Regulatory pathway
  • Reproducibility of Results
  • T-Lymphocytes/immunology
  • Humans
  • Computational Biology/methods
  • Models, Immunological
  • Animals
  • Antigens, CD/immunology
  • Computer Simulation
  • Signal Transduction/immunology
  • Encephalomyelitis, Autoimmune, Experimental/immunology
  • Mice
  • Multiple Sclerosis/immunology
  • Disease Models, Animal

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