Methods for the theoretical analysis of cellular networks

Reinhart Heinrich


I will discuss the ideas behind various methods for analyzing metabolic networks and networks of signal transduction with respect to two different goals, (1) explaining their dynamic behaviour, and (2) understanding their structural design.

(1) Principles of nonlinear dynamics, and bifurcation analysis are outlined with specific examples for intracellular oscillations and intercellular waves. Other methods include metabolic control analysis for identifing key reactions steps, and stoichiometric analysis for identifying specific routes, such as elementary pathways, through complex networks.

(2) I will show how principles of network design can be analyzed by using optimization methods including evolutionary algorithms. Design principles are discussed resulting from specific properties of metabolism (fluxes, homeostasis, stoichiometric robustness), and of signal transduction (amplification, signal duration, dynamic stability). A new method, dynamic network expansion, aims to relate the present day structure of networks to their evolutionary history. Here, extensive use is made of databases for metabolism and signal transduction on a large scale.