TY - JOUR
T1 - In silico investigation of novel biological pathways
T2 - The role of CD200 in regulation of T cell priming in experimental autoimmune encephalomyelitis
AU - Greaves, Richard B.
AU - Read, Mark
AU - Timmis, Jon
AU - Andrews, Paul S.
AU - Butler, James A.
AU - Gerckens, Bjorn Ole
AU - Kumar, Vipin
PY - 2013/5
Y1 - 2013/5
N2 - 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.
AB - 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.
KW - Agent-based simulation
KW - CD200
KW - Experimental autoimmune encephalomyelitis
KW - In silico experimentation
KW - Principled simulation development
KW - Regulatory pathway
UR - http://www.scopus.com/inward/record.url?scp=84877925521&partnerID=8YFLogxK
U2 - 10.1016/j.biosystems.2013.03.007
DO - 10.1016/j.biosystems.2013.03.007
M3 - Article
C2 - 23499816
AN - SCOPUS:84877925521
SN - 0303-2647
VL - 112
SP - 107
EP - 121
JO - Biosystems
JF - Biosystems
IS - 2
ER -