François Fages, Sylvain Soliman:
From Reaction Models to Influence Graphs and Back: a Theorem.

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In: Proceedings of First International Workshop on Formal Methods in Systems Biology (FMSB 2008), Cambridge, UK (4th - 5th June 2008), LNCS 5054, June 2008
© Springer

Biologists use diagrams to represent interactions between molecular species, and on the computer, diagrammatic notations are also more and more employed in interactive maps. These diagrams are fundamentally of two types: reaction graphs and activation/inhibition graphs. In this paper, we study the formal relationship between these graphs. We consider systems of biochemical reactions with kinetic expressions, as written in the Systems Biology Markup Language SBML, and interpreted by a system of Ordinary Differential Equations over molecular concentrations. We show that under a general condition of increasing monotonicity of the kinetic expressions, and in absence of both activation and inhibition effects between a pair of molecules, the influence graph inferred from the stoichiometric coefficients of the reactions is equal to the one defined by the signs of the coefficients of the Jacobian matrix. Under these conditions, satisfied by mass action law, Michaelis-Menten and Hill kinetics, the influence graph is thus independent of the precise kinetic expressions, and is computable in linear time in the number of reactions. We apply these results to Kohn’s map of the mammalian cell cycle and to the MAPK signalling cascade. Then we propose a syntax for denoting antagonists in reaction rules and generalize our results to this setting.



	author = {Fran\c{c}ois Fages and Sylvain Soliman},
	title = {From Reaction Models to Influence Graphs and Back: a Theorem},
	booktitle = {Proceedings of First International Workshop on Formal Methods in Systems Biology, Cambridge, UK (4th--5th June 2008)},
	year = {2008},
	volume = {5054},
	series = {LNCS},
	url = {}