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

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

Date Published: 2013-05

DOI: 10.1016/j.biosystems.2013.03.007

Sponsors: Royal Society United Kingdom Engineering and Physical Sciences Research Council (EPSRC) United States National Institutes of Health (NIH)

Platforms: No platforms listed

Model Documentation: Other Narrative Flow charts

Model Code URLs: Model code not found

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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Tags

agent-based simulation In silico experimentation CD200 Experimental autoimmune Principled simulation development Regulatory pathway encephalomyelitis