TY  - JOUR
EP  - 16
Y1  - 2012///
TI  - Simplification of biochemical models: a general approach based on the analysis of the impact of individual species and reactions on the systems dynamics
SP  - 1
JF  - BMC Systems Biology
VL  - 6
CY  - London
A1  - Surovtsova, Irina
A1  - Simus, Natalia
A1  - Hübner, Katrin
A1  - Sahle, Sven
A1  - Kummer, Ursula
SN  - 1752-0509
AV  - public
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/20076/
IS  - 14
PB  - BioMed Central
ID  - heidok20076
N2  - Background: Given the complex mechanisms underlying biochemical processes systems biology researchers tend to build ever increasing computational models. However, dealing with complex systems entails a variety of problems, e.g. difficult intuitive understanding, variety of time scales or non-identifiable parameters. Therefore, methods are needed that, at least semi-automatically, help to elucidate how the complexity of a model can be reduced such that important behavior is maintained and the predictive capacity of the model is increased. The results should be easily accessible and interpretable. In the best case such methods may also provide insight into fundamental biochemical mechanisms.   Results: We have developed a strategy based on the Computational Singular Perturbation (CSP) method which can be used to perform a "biochemically-driven" model reduction of even large and complex kinetic ODE systems. We provide an implementation of the original CSP algorithm in COPASI (a COmplex PAthway SImulator) and applied the strategy to two example models of different degree of complexity - a simple one-enzyme system and a full-scale model of yeast glycolysis.   Conclusion: The results show the usefulness of the method for model simplification purposes as well as for analyzing fundamental biochemical mechanisms. COPASI is freely available at http://www.copasi.org.
ER  -