Journal of Mathematical Biology

, Volume 70, Issue 7, pp 1669–1684 | Cite as

Implicit dose-response curves

Article

Abstract

We develop tools from computational algebraic geometry for the study of steady state features of autonomous polynomial dynamical systems via elimination of variables. In particular, we obtain nontrivial bounds for the steady state concentration of a given species in biochemical reaction networks with mass-action kinetics. This species is understood as the output of the network and we thus bound the maximal response of the system. The improved bounds give smaller starting boxes to launch numerical methods. We apply our results to the sequential enzymatic network studied in Markevich et al. (J Cell Biol 164(3):353–359, 2004) to find nontrivial upper bounds for the different substrate concentrations at steady state. Our approach does not require any simulation, analytical expression to describe the output in terms of the input, or the absence of multistationarity. Instead, we show how to extract information from effectively computable implicit dose-response curves, with the use of resultants and discriminants. We moreover illustrate in the application to an enzymatic network, the relation between the exact implicit dose-response curve we obtain symbolically and the standard hysteresis diagram provided by a numerical ode solver. The setting and tools we propose could yield many other results adapted to any autonomous polynomial dynamical system, beyond those where it is possible to get explicit expressions.

Keywords

Chemical reaction networks Steady states Bounds  Resultants Maximal response 

Mathematics Subject Classification

92C45 13P15 

Notes

Acknowledgments

This work was partially supported by UBACYT 20020100100242, CONICET PIP 11220110100580 and ANPCyT 2008-0902, Argentina.

Supplementary material

285_2014_809_MOESM1_ESM.txt (3 kb)
Supplementary material 1 (txt 3 KB)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Dto. de Matemática, FCENUniversidad de Buenos Aires, Ciudad UniversitariaBuenos AiresArgentina
  2. 2.Dto. de Ciencias Exactas, CBCUniversidad de Buenos AiresBuenos AiresArgentina
  3. 3.IMAS, CONICETCiudad UniversitariaBuenos AiresArgentina

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