The meaning of sensitivity functions in Signaling Pathways analysis

The paper deals with local sensitivity analysis of signaling path- way models, based on sensitivity functions. Though the methods are well known, their application to various models is always based on the assumption that the output of the system whose sensitivity is analyzed is given by abso- lute quantitative data. In signaling pathways models, however, this data is always normalized. In this paper we show what are the implications of the way the signaling pathways models are built for the interpretation of sensitivity functions and parameter rankings based on them. The reasoning is illustrated using simple first- and second order systems as well as an example of a simple regulatory module.