Parameter Scanning by Parallel Model Checking with Applications in Systems Biology

Abstract

In this paper, a novel scalable method for scanning of kinetic parameter values in continuous (ODE) models of biological networks is provided. The presented method is property-driven, in particular, parameter values are scanned in order to satisfy a given dynamic property. The key result – the parameter scanning method – is based on an innovative adaptation of parallel LTL model checking for the framework of parameterized Kripke structures (PKS). First, we introduce the notion of PKS and we identify the parameter scanning and robustness analysis problems in this framework. Second, we present the algorithms for parallel LTL model checking on PKSs. Finally, the evaluation is provided on case studies of mammalian cell-cycle genetic regulatory network model and E. Coli ammonium transport model.