Sensitivity analysis of signaling pathway models with a model combining HSF and NF-kB signaling pathways as an example

In the speech selected methods of sensitivity analysis will be discussed. Though the sensitivity methods are well known, their application to various models is always based on the assumption that the output of the system is given by absolute quantitative data. In signaling pathway models, however, direct measurements of concentrations are not always feasible, which may skew conclusions stemming from standard sensitivity analysis. Therefore, a new method of sensitivity analysis will be presented that overcomes constraints imposed by experimental methods. The applicability of selected methods will be illustrated with a novel model describing interactions between two signaling pathways: HSF and NF-κB. These two major stress-response pathways interfere with each other in a number of ways. Following heat shock, cells usually do not exhibit cytokine-induced activation of NF-κB and upregulation of classical NF-κB dependent genes, however the precise mechanism of this inhibition is not clear.