TY  - JOUR
A1  - Neigenfind, Jost
A1  - Grimbs, Sergio
A1  - Nikoloski, Zoran
T1  - On the relation between reactions and complexes of (bio)chemical reaction networks
JF  - Journal of theoretical biology
N2  - Robustness of biochemical systems has become one of the central questions in systems biology although it is notoriously difficult to formally capture its multifaceted nature. Maintenance of normal system function depends not only on the stoichiometry of the underlying interrelated components, but also on the multitude of kinetic parameters. Invariant flux ratios, obtained within flux coupling analysis, as well as invariant complex ratios, derived within chemical reaction network theory, can characterize robust properties of a system at steady state. However, the existing formalisms for the description of these invariants do not provide full characterization as they either only focus on the flux-centric or the concentration-centric view. Here we develop a novel mathematical framework which combines both views and thereby overcomes the limitations of the classical methodologies. Our unified framework will be helpful in analyzing biologically important system properties.
KW  - Metabolic network
KW  - Mass action system
KW  - Flux coupling analysis
KW  - Chemical reaction network theory
Y1  - 2013
U6  - https://doi.org/10.1016/j.jtbi.2012.10.016
SN  - 0022-5193
VL  - 317
IS  - 2
SP  - 359
EP  - 365
PB  - Elsevier
CY  - London
ER  - 
TY  - JOUR
A1  - Töpfer, Nadine
A1  - Caldana, Camila
A1  - Grimbs, Sergio
A1  - Willmitzer, Lothar
A1  - Fernie, Alisdair R.
A1  - Nikoloski, Zoran
T1  - Integration of genome-scale modeling and transcript profiling reveals metabolic pathways underlying light and temperature acclimation in arabidopsis
JF  - The plant cell
N2  - Understanding metabolic acclimation of plants to challenging environmental conditions is essential for dissecting the role of metabolic pathways in growth and survival. As stresses involve simultaneous physiological alterations across all levels of cellular organization, a comprehensive characterization of the role of metabolic pathways in acclimation necessitates integration of genome-scale models with high-throughput data. Here, we present an integrative optimization-based approach, which, by coupling a plant metabolic network model and transcriptomics data, can predict the metabolic pathways affected in a single, carefully controlled experiment. Moreover, we propose three optimization-based indices that characterize different aspects of metabolic pathway behavior in the context of the entire metabolic network. We demonstrate that the proposed approach and indices facilitate quantitative comparisons and characterization of the plant metabolic response under eight different light and/or temperature conditions. The predictions of the metabolic functions involved in metabolic acclimation of Arabidopsis thaliana to the changing conditions are in line with experimental evidence and result in a hypothesis about the role of homocysteine-to-Cys interconversion and Asn biosynthesis. The approach can also be used to reveal the role of particular metabolic pathways in other scenarios, while taking into consideration the entirety of characterized plant metabolism.
Y1  - 2013
U6  - https://doi.org/10.1105/tpc.112.108852
SN  - 1040-4651
VL  - 25
IS  - 4
SP  - 1197
EP  - 1211
PB  - American Society of Plant Physiologists
CY  - Rockville
ER  -