1. Max Planck Institute for Dynamics of Complex Technical Systems, D-39106 Magdeburg, Germany
2. Max Delbrück Center for Molecular Medicine, D-13092 Berlin, Germany

Correspondence to: Jörg Stelling¹ Correspondence and requests for materials should be addressed to J.S. (e-mail: Email: stelling@mpi-magdeburg.mpg.de).

The relationship between structure, function and regulation in complex cellular networks is a still largely open question^{1, 2, 3}. Systems biology aims to explain this relationship by combining experimental and theoretical approaches⁴. Current theories have various strengths and shortcomings in providing an integrated, predictive description of cellular networks. Specifically, dynamic mathematical modelling of large-scale networks meets difficulties because the necessary mechanistic detail and kinetic parameters are rarely available. In contrast, structure-oriented analyses only require network topology, which is well known in many cases. Previous approaches of this type focus on network robustness⁵ or metabolic phenotype^{2, 6}, but do not give predictions on cellular regulation. Here, we devise a theoretical method for simultaneously predicting key aspects of network functionality, robustness and gene regulation from network structure alone. This is achieved by determining and analysing the non-decomposable pathways able to operate coherently at steady state (elementary flux modes). We use the example of Escherichia coli central metabolism to illustrate the method.