Combining Boolean Networks and Ordinary Differential Equations for Analysis and Comparison of Gene Regulatory Networks
This thesis is concerned with different groups of qualitative models of gene regulatory networks. Four types of models will be considered: interaction graphs, Boolean networks, models based on differential equations and discrete abstractions of differential equations. We will investigate the relations between these modeling frameworks and how they can be used in the analysis of individual models. The focus lies on the mathematical analysis of these models. This thesis makes several contributions in relating these different modeling frameworks. The first approach concerns individual Boolean models and parametrized families of ordinary differential equations (ODEs). To construct ODE models systematically from Boolean models several automatic conversion algorithms have been proposed. In Chapter 2 several such closely related algorithms will be considered. It will be proven that certain invariant sets are preserved during the conversion from a Boolean network to a model based on ODEs. In the second approach the idea of abstracting the dynamics of individual models to relate structure and dynamics will be introduced. This approach will be applied to Boolean models and models based on differential equations. This allows to compare groups of models in these modeling frameworks which have the same structure. We demonstrate that this constitutes an approach to link the interaction graph to the dynamics of certain sets of Boolean networks and models based on differential equations. The abstracted dynamics – or more precisely the restrictions on the abstracted behavior – of such sets of Boolean networks or models based on differential equations will be represented as Boolean state transitions graphs themselves. We will show that these state transition graphs can be considered as asynchronous Boolean networks. Despite the rather theoretical question this thesis tries to answer there are many potential applications of the results. The results in Chapter 2 can be applied to network reduction of ODE models based on Hill kinetics. The results of the second approach in Chapter 4 can be applied to network inference and analysis of Boolean model sets. Furthermore, in the last chapter of this thesis several ideas for applications with respect to experiment design will be considered. This leads to the question how different asynchronous Boolean networks or different behaviours of a single asynchronous Boolean network can be distinguished.