A Systemc-Based Platform For Assertion-Based Verification And Mutation Analysis In Systems Biology

Boolean models are gaining an increasing interest for reproducing dynamic behaviours, understanding processes, and predicting emerging properties of cellular signalling networks through in-silico experiments. They are emerging as a valid alternative to the quantitative approaches (i.e., based on ordinary differential equations) for exploratory modelling when little is known about reaction kinetics or equilibrium constants in the context of gene expression or signalling. Even though several approaches and software have been recently proposed for logic modelling of biological systems, they are limited to specific modelling contexts and they lack of automation in analysing biological properties such as complex attractors, molecule vulnerability, dose response. This paper presents a design and verification platform based on SystemC that applies methodologies and tools well established in the electronic-design automation (EDA) field such as assertion-based verification (ABV) and mutation analysis, which allow complex attractors (i.e., protein oscillations) and robustness/sensitivity of the signalling networks to be simulated and analysed. The paper reports the results obtained by applying such verification techniques for the analysis of the intracellular signalling network controlling integrin activation mediating leukocyte recruitment from the blood into the tissues.