Power-law modeling based on least-squares criteria: consequences for system analysis and simulation.

The power-law formalism was initially derived as a Taylor series approximation in logarithmic space for kinetic rate-laws. The resulting models, either as generalized mass action (GMA) or as S-systems models, allow to characterize the target system and to simulate its dynamical behavior in response to external perturbations and parameter changes. This approach has been succesfully used as a modeling tool in many applications from cell metabolism to population dynamics. Without leaving the general formalism, we recently proposed to derive the power-law representation in an alternative way that uses least-squares (LS) minimization instead of the traditional derivation based on Taylor series [B. Hernández-Bermejo, V. Fairén, A. Sorribas, Math. Biosci. 161 (1999) 83-94]. It was shown that the resulting LS power-law mimics the target rate-law in a wider range of concentration values than the classical power-law, and that the prediction of the steady-state using the LS power-law is closer to the actual steady-state of the target system. However, many implications of this alternative approach remained to be established. We explore some of them in the present work. Firstly, we extend the definition of the LS power-law within a given operating interval in such a way that no preferred operating point is selected. Besides providing an alternative to the classical Taylor power-law, that can be considered a particular case when the operating interval is reduced to a single point, the LS power-law so defined is consistent with the results that can be obtained by fitting experimental data points. Secondly, we show that the LS approach leads to a system description, either as an S-system or a GMA model, in which the systemic properties (such as the steady-state prediction or the log-gains) appear averaged over the corresponding interval when compared with the properties that can be computed from Taylor-derived models in different operating points within the considered operating range. Finally, we also show that the LS description leads to a global, accurate description of the system when it is submitted to external forcing.

Power-law modeling based on least-squares minimization criteria.

The power-law formalism has been successfully used as a modeling tool in many applications. The resulting models, either as Generalized Mass Action or as S-systems models, allow one to characterize the target system and to simulate its dynamical behavior in response to external perturbations and parameter changes. The power-law formalism was first derived as a Taylor series approximation in logarithmic space for kinetic rate-laws. The especial characteristics of this approximation produce an extremely useful systemic representation that allows a complete system characterization. Furthermore, their parameters have a precise interpretation as local sensitivities of each of the individual processes and as rate-constants. This facilitates a qualitative discussion and a quantitative estimation of their possible values in relation to the kinetic properties. Following this interpretation, parameter estimation is also possible by relating the systemic behavior to the underlying processes. Without leaving the general formalism, in this paper we suggest deriving the power-law representation in an alternative way that uses least-squares minimization. The resulting power-law mimics the target rate-law in a wider range of concentration values than the classical power-law. Although the implications of this alternative approach remain to be established, our results show that the predicted steady-state using the least-squares power-law is closest to the actual steady-state of the target system.

Graph-theoretic description of the interplay between non-linearity and connectivity in biological systems.

The purpose of this article is to stress the implications that the consideration of nonlinearity has upon the extension and strength of connectivity, if this is understood as a characterization of the degree of interrelation between parts of the system. This objective is reached within the QP formalism for non-linear ODEs. The formalism is developed in a graph-theoretic setting, with the help of which the connectionist aspect of non-linearity becomes apparent. Topology-preserving transformations involve an exchange between the degree of non-linearity and the strengths of interactions, thus assembling systems of apparently different nature into classes of equivalence. We argue that, if we have in mind a classification of systems according to behavior, these classes of equivalence should be given their proper singularity. We characterize globally the connectivity of a class with an index, although we point out during the discussion that the mathematical conception of the complex idea of connectivity is still incomplete.

Lotka-Volterra representation of general nonlinear systems.

In this article we elaborate on the structure of the generalized Lotka-Volterra (GLV) form for nonlinear differential equations. We discuss here the algebraic properties of the GLV family, such as the invariance under quasimonomial transformations and the underlying structure of classes of equivalence. Each class possesses a unique representative under the classical quadratic Lotka-Volterra form. We show how other standard modeling forms of biological interest, such as S-systems or mass-action systems, are naturally embedded into the GLV form, which thus provides a formal framework for their comparison and for the establishment of transformation rules. We also focus on the issue of recasting of general nonlinear systems into the GLV format. We present a procedure for doing so and point at possible sources of ambiguity that could make the resulting Lotka-Volterra system dependent on the path followed. We then provide some general theorems that define the operational and algorithmic framework in which this is not the case.