Multi-parameter exploration of dynamics of regulatory networks

Abstract

Over the last twenty years advances in systems biology have changed our views on microbial communities and promise to revolutionize treatment of human diseases. In almost all scientific breakthroughs since time of Newton, mathematical modeling has played a prominent role. Regulatory networks emerged as preferred descriptors of how abundances of molecular species depend on each other. However, the central question on how cellular phenotypes emerge from dynamics of these network remains elusive. The principal reason is that differential equation models in the field of biology (while so successful in areas of physics and physical chemistry), do not arise from first principles, and these models suffer from lack of proper parameterization. In response to these challenges, discrete time models based on Boolean networks have been developed. In this review, we discuss an emerging modeling paradigm that combines ideas from differential equations and Boolean models, and has been developed independently within dynamical systems and computer science communities. The result is an approach that can associate a range of potential dynamical behaviors to a network, arrange the descriptors of the dynamics in a searchable database, and allows for multi-parameter exploration of the dynamics akin to bifurcation theory. Since this approach is computationally accessible for moderately sized networks, it allows, perhaps for the first time, to rationally compare different network topologies based on their dynamics.