A Promising Method for Calculating True Steady-State Metabolite Concentrations in Large-Scale Metabolic Reaction Network Models
| Autor: | Atsuko Miyawaki-Kuwakado, Soichiro Komori, Fumihide Shiraishi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Steady state (electronics)
Differential equation Systems Biology Applied Mathematics Numerical analysis Citric Acid Cycle Rate equation Models Biological Nonlinear system Convergence (routing) Linear Models Genetics Applied mathematics Sensitivity (control systems) Algorithms Metabolic Networks and Pathways Biotechnology Network model Mathematics |
| Zdroj: | IEEE/ACM Transactions on Computational Biology and Bioinformatics. 17:27-36 |
| ISSN: | 2374-0043 1545-5963 |
| DOI: | 10.1109/tcbb.2018.2853724 |
| Popis: | The calculation of steady-state metabolite concentrations in metabolic reaction network models is the first step in the sensitivity analysis of a metabolic reaction system described by differential equations. However, this calculation becomes very difficult when the number of differential equations is more than 100. In the present study, therefore, we investigated a calculation procedure for obtaining true steady-state metabolite concentrations both efficiently and accurately even in large-scale network models. For convenience, a linear pathway model composed of a simple Michaelis-Menten rate law and two TCA cycle models were used as case studies. The calculation procedure is as follows: first solve the differential equations by a numerical method for solving initial-value problems until the upper several digits of the calculated values stabilize, and then use these values as initial guesses for a root-finding technique. An intensive investigation indicates that the S-system technique, finding roots in logarithmic space and providing a broader convergence region, is superior to the Newton-Raphson technique, and the algorithm using the S-system technique successfully provides true steady-state values with machine accuracy even with 1,500 differential equations. The complex-step method is also shown to contribute to shortening the calculation time and enhancing the accuracy. The program code has been deposited to https://github.com/BioprocessdesignLab/Steadystateconc . |
| Databáze: | OpenAIRE |
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