A simple and highly accurate numerical differentiation method for sensitivity analysis of large-scale metabolic reaction systems

Fumihide Shiraishi, Shingo Furuta, Takaaki Ishimatsu, Jarin Akhter

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17 Citations (Scopus)


Numerical differentiation is known to be one of the most difficult numerical calculation methods to obtain reliable calculated values at all times. A simple numerical differentiation method using a combination of finite-difference formulas, derived by approximation of Taylor-series equations, is investigated in order to efficiently perform the sensitivity analysis of large-scale metabolic reaction systems. A result of the application to four basic mathematical functions reveals that the use of the eight-point differentiation formula with a non-dimensionalized stepsize close to 0.01 mostly provides more than 14 digits of accuracy in double precision for the numerical derivatives. Moreover, a result of the application to the modified TCA cycle model indicates that the numerical differentiation method gives the calculated values of steady-state metabolite concentrations within a range of round-off error and also makes it possible to transform the Michaelis-Menten equations into the S-system equations having the kinetic orders whose accuracies are mostly more than 14 significant digits. Because of the simple structure of the numerical differentiation formula and its promising high accuracy, it is evident that the present numerical differentiation method is useful for the analysis of large-scale metabolic reaction systems according to the systematic procedure of BST.

Original languageEnglish
Pages (from-to)590-606
Number of pages17
JournalMathematical Biosciences
Issue number2
Publication statusPublished - Aug 1 2007


All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Modelling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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