Abstract
SummaryAt the cellular level, cancer is triggered by mutations of the proteins involved in signalling networks made of hundreds of reacting species. The corresponding mathematical model consists of a large system of non-linear Ordinary Differential Equations for the unknown proteins concentrations depending on a consistently large number of kinetic parameters and initial concentrations. For this model, the present paper considers the problem of assessing the impact of each parameter and initial concentration on the system’s output. More specifically, we introduced a statistical sensitivity index whose values can be easily computed by means of principal component analysis, and which leads to the partition of the parameters’ and initial concentrations’ sets into sensible and non-sensible families. This approach allows the identification of those kinetic parameters and initial concentrations that mostly impact the mutation-driven modification of the proteomic profile at equilibrium, and of those pathways in the network that are mostly affected by the presence of mutations in the cancer cell.
Publisher
Cold Spring Harbor Laboratory
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