Structurally robust biological networks

Background: The molecular circuitry of living organisms performs remarkably robust regulatory tasks, despite the often intrinsic variability of its components. A large body of research has in fact highlighted that robustness is often a structural property of biological systems. However, there are few systematic methods to mathematically model and describe structural robustness. With a few exceptions, numerical studies are often the preferred approach to this type of investigation. Results: In this paper, we propose a framework to analyze robust stability of equilibria in biological networks. We employ Lyapunov and invariant sets theory, focusing on the structure of ordinary differential equation models. Without resorting to extensive numerical simulations, often necessary to explore the behavior of a model in its parameter space, we provide rigorous proofs of robust stability of known bio-molecular networks. Our results are in line with existing literature. Conclusions: The impact of our results is twofold: on the one hand, we highlight that classical and simple control theory methods are extremely useful to characterize the behavior of biological networks analytically. On the other hand, we are able to demonstrate that some biological networks are robust thanks to their structure and some qualitative properties of the interactions, regardless of the specific values of their parameters

Integral population control of a quadratic dimerization process

Moment control of a simple quadratic reaction network describing a dimerization process is addressed. It is shown that the moment closure problem can be circumvented without invoking any moment closure technique. Local stabilization and convergence of the average dimer population to any desired reference value is ensured using a pure integral control law. Explicit bounds on the controller gain are provided and shown to be valid for any reference value. As a byproduct, an explicit upper-bound of the variance of the monomer species, acting on the system as unknown input due to the moment openness, is obtained. The obtained results are illustrated by an example relying on the simulation of a cell population using stochastic simulation algorithms.Comment: 7 pages; 3 figures; accepted at the 52nd IEEE Conference on Decision and Contro

Transient cognitive dynamics, metastability, and decision making

Transient Cognitive Dynamics, Metastability, and Decision Making. Rabinovich et al. PLoS Computational Biology. 2008. 4(5) doi:10.1371/journal.pcbi.1000072The idea that cognitive activity can be understood using nonlinear dynamics has been intensively discussed at length for the last 15 years. One of the popular points of view is that metastable states play a key role in the execution of cognitive functions. Experimental and modeling studies suggest that most of these functions are the result of transient activity of large-scale brain networks in the presence of noise. Such transients may consist of a sequential switching between different metastable cognitive states. The main problem faced when using dynamical theory to describe transient cognitive processes is the fundamental contradiction between reproducibility and flexibility of transient behavior. In this paper, we propose a theoretical description of transient cognitive dynamics based on the interaction of functionally dependent metastable cognitive states. The mathematical image of such transient activity is a stable heteroclinic channel, i.e., a set of trajectories in the vicinity of a heteroclinic skeleton that consists of saddles and unstable separatrices that connect their surroundings. We suggest a basic mathematical model, a strongly dissipative dynamical system, and formulate the conditions for the robustness and reproducibility of cognitive transients that satisfy the competing requirements for stability and flexibility. Based on this approach, we describe here an effective solution for the problem of sequential decision making, represented as a fixed time game: a player takes sequential actions in a changing noisy environment so as to maximize a cumulative reward. As we predict and verify in computer simulations, noise plays an important role in optimizing the gain.This work was supported by ONR N00014-07-1-0741. PV acknowledges support from Spanish BFU2006-07902/BFI and CAM S-SEM-0255-2006

Robust detection, isolation and accommodation for sensor failures

The objective is to extend the recent advances in robust control system design of multivariable systems to sensor failure detection, isolation, and accommodation (DIA), and estimator design. This effort provides analysis tools to quantify the trade-off between performance robustness and DIA sensitivity, which are to be used to achieve higher levels of performance robustness for given levels of DIA sensitivity. An innovations-based DIA scheme is used. Estimators, which depend upon a model of the process and process inputs and outputs, are used to generate these innovations. Thresholds used to determine failure detection are computed based on bounds on modeling errors, noise properties, and the class of failures. The applicability of the newly developed tools are demonstrated on a multivariable aircraft turbojet engine example. A new concept call the threshold selector was developed. It represents a significant and innovative tool for the analysis and synthesis of DiA algorithms. The estimators were made robust by introduction of an internal model and by frequency shaping. The internal mode provides asymptotically unbiased filter estimates.The incorporation of frequency shaping of the Linear Quadratic Gaussian cost functional modifies the estimator design to make it suitable for sensor failure DIA. The results are compared with previous studies which used thresholds that were selcted empirically. Comparison of these two techniques on a nonlinear dynamic engine simulation shows improved performance of the new method compared to previous technique

Data-based mechanistic modelling, forecasting, and control.

This article briefly reviews the main aspects of the generic data based mechanistic (DBM) approach to modeling stochastic dynamic systems and shown how it is being applied to the analysis, forecasting, and control of environmental and agricultural systems. The advantages of this inductive approach to modeling lie in its wide range of applicability. It can be used to model linear, nonstationary, and nonlinear stochastic systems, and its exploitation of recursive estimation means that the modeling results are useful for both online and offline applications. To demonstrate the practical utility of the various methodological tools that underpin the DBM approach, the article also outlines several typical, practical examples in the area of environmental and agricultural systems analysis, where DBM models have formed the basis for simulation model reduction, control system design, and forecastin