Artículo

Pérez Millán, M.; Dickenstein, A. "Implicit dose-response curves" (2015) Journal of Mathematical Biology. 70(7):1669-1684
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

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. © 2014, Springer-Verlag Berlin Heidelberg.

Registro:

Documento: Artículo
Título:Implicit dose-response curves
Autor:Pérez Millán, M.; Dickenstein, A.
Filiación:Dto. de Matemática, FCEN, Universidad de Buenos Aires, Ciudad Universitaria, Pab. I, Buenos Aires, C1428EGA, Argentina
Dto. de Ciencias Exactas, CBC, Universidad de Buenos Aires, Ramos Mejía 841, Buenos Aires, C1405CAE, Argentina
IMAS, CONICET, Ciudad Universitaria, Pab. I, Buenos Aires, C1428EGA, Argentina
Palabras clave:Bounds; Chemical reaction networks; Maximal response; Resultants; Steady states; enzyme; biological model; dose response; kinetics; mathematical phenomena; metabolism; phosphorylation; signal transduction; systems biology; Dose-Response Relationship, Drug; Enzymes; Kinetics; MAP Kinase Signaling System; Mathematical Concepts; Metabolic Networks and Pathways; Models, Biological; Phosphorylation; Systems Biology
Año:2015
Volumen:70
Número:7
Página de inicio:1669
Página de fin:1684
DOI: http://dx.doi.org/10.1007/s00285-014-0809-4
Título revista:Journal of Mathematical Biology
Título revista abreviado:J. Math. Biol.
ISSN:03036812
CAS:Enzymes
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03036812_v70_n7_p1669_PerezMillan

Referencias:

  • Cox, D., Little, J., O’Shea, D., (2007) Ideals, varieties and algorithms. Undergraduate texts in Mathematics, , Springer, New York:
  • http://www.singular.uni-kl.de, Decker W, Greuel G-M, Pfister G, Schönemann H (2012) Singular 3-1-6: a computer algebra system for polynomial computations; Feinberg, M., (1979) Lectures on chemical reaction networks, , http://www.crnt.osu.edu/LecturesOnReactionNetworks, Ohio State University, Columbus:
  • Feinberg, M., Horn, F., Chemical mechanism structure and the coincidence of the stoichiometric and kinetic subspaces (1977) Arch Ration Mech Anal, 66 (1), pp. 83-97
  • Feliu, E., Wiuf, C., Enzyme-sharing as a cause of multi-stationarity in signalling systems (2012) J R Soc Interface, 9 (71), pp. 1224-1232
  • Feliu, E., Knudsen, M., Andersen, L., Wiuf, C., An algebraic approach to signaling cascades with(Formula presented.) layers (2012) Bull Math Biol, 74 (1), pp. 45-72
  • Flockerzi, D., Holstein, K., Conradi, C., N-site phosphorylation systems with 2N–1 steady states (2013) Available at arXiv, 1312, p. 4774. , arXiv:1312.4774
  • Gelf’and, I., Kapranov, M., Zelevinsky, A., (1994) Discriminants, resultants and multidimensional determinants, , Birkhäuser, Boston:
  • Horn, F., Jackson, R., General mass action kinetics (1972) Arch Ration Mech Anal, 47 (2), pp. 81-116
  • Karp, R., Pérez Millán, M., Dasgupta, T., Dickenstein, A., Gunawardena, J., Complex-linear invariants of biochemical networks (2012) J Theor Biol, 311, pp. 130-138
  • 17, M., (2013) Maplesoft: a division of Waterloo Maple Inc., , Waterloo, Ontario:
  • Markevich, N., Hoek, J., Kholodenko, B., Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades (2004) J Cell Biol, 164 (3), pp. 353-359
  • (2014) version 8.3.0. Natick, , Massachusetts: The MathWorks Inc
  • Pérez Millán, M., Dickenstein, A., Shiu, A., Conradi, C., Chemical reaction systems with toric steady states (2012) Bull Math Biol, 74 (5), pp. 1027-1065
  • Shafarevich, I., (1994) Basic algebraic geometry 1. Varieties in projective space, , Springer, Berlin:
  • Tobis, E.A., Libraries for counting real roots, Reports on computer algebra, ZCA (2005) University of Kaiserslautern, p. 34
  • Vol’pert, A.I., Hudjaev, S.I., (1985) Analysis in classes of discontinuous functions and equations of mathematical physics, vol 8. Mechanics: analysis, , Martinus Nijhoff Publishers, Dordrecht:
  • Wang, L., Sontag, E., On the number of steady states in a multiple futile cycle (2008) J Math Biol, 57 (1), pp. 29-52

Citas:

---------- APA ----------
Pérez Millán, M. & Dickenstein, A. (2015) . Implicit dose-response curves. Journal of Mathematical Biology, 70(7), 1669-1684.
http://dx.doi.org/10.1007/s00285-014-0809-4
---------- CHICAGO ----------
Pérez Millán, M., Dickenstein, A. "Implicit dose-response curves" . Journal of Mathematical Biology 70, no. 7 (2015) : 1669-1684.
http://dx.doi.org/10.1007/s00285-014-0809-4
---------- MLA ----------
Pérez Millán, M., Dickenstein, A. "Implicit dose-response curves" . Journal of Mathematical Biology, vol. 70, no. 7, 2015, pp. 1669-1684.
http://dx.doi.org/10.1007/s00285-014-0809-4
---------- VANCOUVER ----------
Pérez Millán, M., Dickenstein, A. Implicit dose-response curves. J. Math. Biol. 2015;70(7):1669-1684.
http://dx.doi.org/10.1007/s00285-014-0809-4