systematic analysis of stability patterns in plant primary metabolism系统分析在植物初级代谢稳定的模式.pdf

Systematic Analysis of Stability Patterns in Plant Primary Metabolism 1 2 1,2 Dorothee Girbig *, Sergio Grimbs , Joachim Selbig 1 Max-Planck Institute for Molecular Plant Physiology, Potsdam, Germany, 2 Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany Abstract Metabolic networks are characterized by complex interactions and regulatory mechanisms between many individual components. These interactions determine whether a steady state is stable to perturbations. Structural kinetic modeling (SKM) is a framework to analyze the stability of metabolic steady states that allows the study of the system Jacobian without requiring detailed knowledge about individual rate equations. Stability criteria can be derived by generating a large number of structural kinetic models (SK-models) with randomly sampled parameter sets and evaluating the resulting Jacobian matrices. Until now, SKM experiments applied univariate tests to detect the network components with the largest influence on stability. In this work, we present an extended SKM approach relying on supervised machine learning to detect patterns of enzyme-metabolite interactions that act together in an orchestrated manner to ensure stability. We demonstrate its application on a detailed SK-model of the Calvin-Benson cycle and connected pathways. The identified stability patterns are highly complex reflecting that changes in dynamic properties depend on concerted interactions between several network components. In total, we find more patterns that reliably ensure stability than patterns ensuring instability. This shows that the design of this system is strongly targeted towards maintaining stability. We also investigate the effect of allosteric r