Analysis of ERK dynamics using SQUAD and its add-on SQUADD

Logical modeling is increasingly popular method in system biology to explain and predict the behavior of a complex process (differentiation, cell growth, division etc. . . ) through their regulatory and signalling mechanisms. The SQUAD software (Standardized Qualitative Dynamical Systems) is dedicated to the analysis of Boolean logical models [1]. It was the first tool to combine the traditional Boolean approach and a continuous system. This novel feature permits the dynamical analysis of regulatory network in the absence of kinetic data ([6], [5], [1]). In order to improve this approach, we provide the R package SQUADD, the SQUAD add-on. It is built in respect to S4 classes and the methods convention. This extension permits: (i) to simplify the visualization of the initial SQUAD simulation output, (ii) to generate qualitative predictions of the component change between two conditions and (iii) to assess the coherence of a network model using PCA analysis. The SQUADD uses are illustrated on the simplified model of the ERK signaling in mammalian cells. The ERK cascade is composed of three major kinase components, RAF MEK and ERK.