arXiv subjects

Aivar Sootla

Publications and source records attributed to Aivar Sootla.

31 records · Page 2Linked to original sources

arXiv2017

Pulse-Based Control Using Koopman Operator Under Parametric Uncertainty

In applications, such as biomedicine and systems/synthetic biology, technical limitations in actuation complicate implementation of time-varying control signals. In order to alleviate some of these limitations, it may be desirable to derive simple control policies, such as step functions with fixed magnitude and length (or temporal pulses). In this technical note, we further develop a recently proposed pulse-based solution to the convergence problem, i.e., minimizing the convergence time to the target exponentially stable equilibrium, for monotone systems. In particular, we extend this solution to monotone systems with parametric uncertainty. Our solutions also provide worst-case estimates on convergence times. Furthermore, we indicate how our tools can be used for a class of non-monotone systems, and more importantly how these tools can be extended to other control problems. We illustrate our approach on switching under parametric uncertainty and regulation around a saddle point problems in a genetic toggle switch system.

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arXiv2017

Operator-Theoretic Characterization of Eventually Monotone Systems

Monotone systems are dynamical systems whose solutions preserve a partial order in the initial condition for all positive times. It stands to reason that some systems may preserve a partial order only after some initial transient. These systems are usually called eventually monotone. While monotone systems have a characterization in terms of their vector fields (i.e. Kamke-Muller condition), eventually monotone systems have not been characterized in such an explicit manner. In order to provide a characterization, we drew inspiration from the results for linear systems, where eventually monotone (positive) systems are studied using the spectral properties of the system (i.e. Perron-Frobenius property). In the case of nonlinear systems, this spectral characterization is not straightforward, a fact that explains why the class of eventually monotone systems has received little attention to date. In this paper, we show that a spectral characterization of nonlinear eventually monotone systems can be obtained through the Koopman operator framework. We consider a number of biologically inspired examples to illustrate the potential applicability of eventual monotonicity.

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arXiv2017

Geometric Properties of Isostables and Basins of Attraction of Monotone Systems

In this paper, we study geometric properties of basins of attraction of monotone systems. Our results are based on a combination of monotone systems theory and spectral operator theory. We exploit the framework of the Koopman operator, which provides a linear infinite-dimensional description of nonlinear dynamical systems and spectral operator-theoretic notions such as eigenvalues and eigenfunctions. The sublevel sets of the dominant eigenfunction form a family of nested forward-invariant sets and the basin of attraction is the largest of these sets. The boundaries of these sets, called isostables, allow studying temporal properties of the system. Our first observation is that the dominant eigenfunction is increasing in every variable in the case of monotone systems. This is a strong geometric property which simplifies the computation of isostables. We also show how variations in basins of attraction can be bounded under parametric uncertainty in the vector field of monotone systems. Finally, we study the properties of the parameter set for which a monotone system is multistable. Our results are illustrated on several systems of two to four dimensions.

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arXiv2016

Shaping Pulses to Control Bistable Monotone Systems Using Koopman Operator

In this paper, we further develop a recently proposed control method to switch a bistable system between its steady states using temporal pulses. The motivation for using pulses comes from biomedical and biological applications (e.g. synthetic biology), where it is generally difficult to build feedback control systems due to technical limitations in sensing and actuation. The original framework was derived for monotone systems and all the extensions relied on monotone systems theory. In contrast, we introduce the concept of switching function which is related to eigenfunctions of the so-called Koopman operator subject to a fixed control pulse. Using the level sets of the switching function we can (i) compute the set of all pulses that drive the system toward the steady state in a synchronous way and (ii) estimate the time needed by the flow to reach an epsilon neighborhood of the target steady state. Additionally, we show that for monotone systems the switching function is also monotone in some sense, a property that can yield efficient algorithms to compute it. This observation recovers and further extends the results of the original framework, which we illustrate on numerical examples inspired by biological applications.

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arXiv2016

Properties of Isostables and Basins of Attraction of Monotone Systems

In this paper, we investigate geometric properties of monotone systems by studying their isostables and basins of attraction. Isostables are boundaries of specific forward-invariant sets defined by the so-called Koopman operator, which provides a linear infinite-dimensional description of a nonlinear system. First, we study the spectral properties of the Koopman operator and the associated semigroup in the context of monotone systems. Our results generalize the celebrated Perron-Frobenius theorem to the nonlinear case and allow us to derive geometric properties of isostables and basins of attraction. Additionally, we show that under certain conditions we can characterize the bounds on the basins of attraction under parametric uncertainty in the vector field. We discuss computational approaches to estimate isostables and basins of attraction and illustrate the results on two and four state monotone systems.

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arXiv2015

Structured Projection-Based Model Reduction with Application to Stochastic Biochemical Networks

The Chemical Master Equation (CME) is well known to provide the highest resolution models of a biochemical reaction network. Unfortunately, even simulating the CME can be a challenging task. For this reason more simple approximations to the CME have been proposed. In this work we focus on one such model, the Linear Noise Approximation. Specifically, we consider implications of a recently proposed LNA time-scale separation method. We show that the reduced order LNA converges to the full order model in the mean square sense. Using this as motivation we derive a network structure preserving reduction algorithm based on structured projections. We present convex optimisation algorithms that describe how such projections can be computed and we discuss when structured solutions exits. We also show that for a certain class of systems, structured projections can be found using basic linear algebra and no optimisation is necessary. The algorithms are then applied to a linearised stochastic LNA model of the yeast glycolysis pathway.

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arXiv2015

Shaping Pulses to Control Bistable Biological Systems

In this paper we study how to shape temporal pulses to switch a bistable system between its stable steady states. Our motivation for pulse-based control comes from applications in synthetic biology, where it is generally difficult to implement real-time feedback control systems due to technical limitations in sensors and actuators. We show that for monotone bistable systems, the estimation of the set of all pulses that switch the system reduces to the computation of one non-increasing curve. We provide an efficient algorithm to compute this curve and illustrate the results with a genetic bistable system commonly used in synthetic biology. We also extend these results to models with parametric uncertainty and provide a number of examples and counterexamples that demonstrate the power and limitations of the current theory. In order to show the full potential of the framework, we consider the problem of inducing oscillations in a monotone biochemical system using a combination of temporal pulses and event-based control. Our results provide an insight into the dynamics of bistable systems under external inputs and open up numerous directions for future investigation.

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arXiv2015

On Monotonicity and Propagation of Order Properties

In this paper, a link between monotonicity of deterministic dynamical systems and propagation of order by Markov processes is established. The order propagation has received considerable attention in the literature, however, this notion is still not fully understood. The main contribution of this paper is a study of the order propagation in the deterministic setting, which potentially can provide new techniques for analysis in the stochastic one. We take a close look at the propagation of the so-called increasing and increasing convex orders. Infinitesimal characterisations of these orders are derived, which resemble the well-known Kamke conditions for monotonicity. It is shown that increasing order is equivalent to the standard monotonicity, while the class of systems propagating the increasing convex order is equivalent to the class of monotone systems with convex vector fields. The paper is concluded by deriving a novel result on order propagating diffusion processes and an application of this result to biological processes.

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arXiv2015

Toggling a Genetic Switch Using Reinforcement Learning

In this paper, we consider the problem of optimal exogenous control of gene regulatory networks. Our approach consists in adapting an established reinforcement learning algorithm called the fitted Q iteration. This algorithm infers the control law directly from the measurements of the system's response to external control inputs without the use of a mathematical model of the system. The measurement data set can either be collected from wet-lab experiments or artificially created by computer simulations of dynamical models of the system. The algorithm is applicable to a wide range of biological systems due to its ability to deal with nonlinear and stochastic system dynamics. To illustrate the application of the algorithm to a gene regulatory network, the regulation of the toggle switch system is considered. The control objective of this problem is to drive the concentrations of two specific proteins to a target region in the state space.

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arXiv2014

Distributed Reconstruction of Nonlinear Networks: An ADMM Approach

In this paper, we present a distributed algorithm for the reconstruction of large-scale nonlinear networks. In particular, we focus on the identification from time-series data of the nonlinear functional forms and associated parameters of large-scale nonlinear networks. Recently, a nonlinear network reconstruction problem was formulated as a nonconvex optimisation problem based on the combination of a marginal likelihood maximisation procedure with sparsity inducing priors. Using a convex-concave procedure (CCCP), an iterative reweighted lasso algorithm was derived to solve the initial nonconvex optimisation problem. By exploiting the structure of the objective function of this reweighted lasso algorithm, a distributed algorithm can be designed. To this end, we apply the alternating direction method of multipliers (ADMM) to decompose the original problem into several subproblems. To illustrate the effectiveness of the proposed methods, we use our approach to identify a network of interconnected Kuramoto oscillators with different network sizes (500~100,000 nodes).

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arXiv2014

On Projection-Based Model Reduction of Biochemical Networks-- Part II: The Stochastic Case

In this paper, we consider the problem of model order reduction of stochastic biochemical networks. In particular, we reduce the order of (the number of equations in) the Linear Noise Approximation of the Chemical Master Equation, which is often used to describe biochemical networks. In contrast to other biochemical network reduction methods, the presented one is projection-based. Projection-based methods are powerful tools, but the cost of their use is the loss of physical interpretation of the nodes in the network. In order alleviate this drawback, we employ structured projectors, which means that some nodes in the network will keep their physical interpretation. For many models in engineering, finding structured projectors is not always feasible; however, in the context of biochemical networks it is much more likely as the networks are often (almost) monotonic. To summarise, the method can serve as a trade-off between approximation quality and physical interpretation, which is illustrated on numerical examples.

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arXiv2014

On Projection-Based Model Reduction of Biochemical Networks-- Part I: The Deterministic Case

This paper addresses the problem of model reduction for dynamical system models that describe biochemical reaction networks. Inherent in such models are properties such as stability, positivity and network structure. Ideally these properties should be preserved by model reduction procedures, although traditional projection based approaches struggle to do this. We propose a projection based model reduction algorithm which uses generalised block diagonal Gramians to preserve structure and positivity. Two algorithms are presented, one provides more accurate reduced order models, the second provides easier to simulate reduced order models. The results are illustrated through numerical examples.

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arXiv2013

On Periodic Reference Tracking Using Batch-Mode Reinforcement Learning with Application to Gene Regulatory Network Control

In this paper, we consider the periodic reference tracking problem in the framework of batch-mode reinforcement learning, which studies methods for solving optimal control problems from the sole knowledge of a set of trajectories. In particular, we extend an existing batch-mode reinforcement learning algorithm, known as Fitted Q Iteration, to the periodic reference tracking problem. The presented periodic reference tracking algorithm explicitly exploits a priori knowledge of the future values of the reference trajectory and its periodicity. We discuss the properties of our approach and illustrate it on the problem of reference tracking for a synthetic biology gene regulatory network known as the generalised repressilator. This system can produce decaying but long-lived oscillations, which makes it an interesting system for the tracking problem. In our companion paper we also take a look at the regulation problem of the toggle switch system, where the main goal is to drive the system's states to a specific bounded region in the state space.

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