The Impact of Time Delays on the Robustness of Biological Oscillators and the Effect of Bifurcations on the Inverse Problem

Differential equation models for biological oscillators are often not robust with respect to parameter variations. They are based on chemical reaction kinetics, and solutions typically converge to a fixed point. This behavior is in contrast to real biological oscillators, which work reliably under varying conditions. Moreover, it complicates network inference from time series data. This paper investigates differential equation models for biological oscillators from two perspectives. First, we investigate the effect of time delays on the robustness of these oscillator models. In particular, we provide sufficient conditions for a time delay to cause oscillations by destabilizing a fixed point in two-dimensional systems. Moreover, we show that the inclusion of a time delay also stabilizes oscillating behavior in this way in larger networks. The second part focuses on the inverse problem of estimating model parameters from time series data. Bifurcations are related to nonsmoothness and multiple local minima of the objective function

Data based identification and prediction of nonlinear and complex dynamical systems

We thank Dr. R. Yang (formerly at ASU), Dr. R.-Q. Su (formerly at ASU), and Mr. Zhesi Shen for their contributions to a number of original papers on which this Review is partly based. This work was supported by ARO under Grant No. W911NF-14-1-0504. W.-X. Wang was also supported by NSFC under Grants No. 61573064 and No. 61074116, as well as by the Fundamental Research Funds for the Central Universities, Beijing Nova Programme.Peer reviewedPostprin

Kinetic Intersections as a Source of Information on Rate Coefficients

C

Stochastic analysis of nonlinear dynamics and feedback control for gene regulatory networks with applications to synthetic biology

The focus of the thesis is the investigation of the generalized repressilator model (repressing genes ordered in a ring structure). Using nonlinear bifurcation analysis stable and quasi-stable periodic orbits in this genetic network are characterized and a design for a switchable and controllable genetic oscillator is proposed. The oscillator operates around a quasi-stable periodic orbit using the classical engineering idea of read-out based control. Previous genetic oscillators have been designed around stable periodic orbits, however we explore the possibility of quasi-stable periodic orbit expecting better controllability. The ring topology of the generalized repressilator model has spatio-temporal symmetries that can be understood as propagating perturbations in discrete lattices. Network topology is a universal cross-discipline transferable concept and based on it analytical conditions for the emergence of stable and quasi-stable periodic orbits are derived. Also the length and distribution of quasi-stable oscillations are obtained. The findings suggest that long-lived transient dynamics due to feedback loops can dominate gene network dynamics. Taking the stochastic nature of gene expression into account a master equation for the generalized repressilator is derived. The stochasticity is shown to influence the onset of bifurcations and quality of oscillations. Internal noise is shown to have an overall stabilizing effect on the oscillating transients emerging from the quasi-stable periodic orbits. The insights from the read-out based control scheme for the genetic oscillator lead us to the idea to implement an algorithmic controller, which would direct any genetic circuit to a desired state. The algorithm operates model-free, i.e. in principle it is applicable to any genetic network and the input information is a data matrix of measured time series from the network dynamics. The application areas for readout-based control in genetic networks range from classical tissue engineering to stem cells specification, whenever a quantitatively and temporarily targeted intervention is required

Synchrony and bifurcations in coupled dynamical systems and effects of time delay

Dynamik auf Netzwerken ist ein mathematisches Feld, das in den letzten Jahrzehnten schnell gewachsen ist und Anwendungen in zahlreichen Disziplinen wie z.B. Physik, Biologie und Soziologie findet. Die Funktion vieler Netzwerke hängt von der Fähigkeit ab, die Elemente des Netzwerkes zu synchronisieren. Mit anderen Worten, die Existenz und die transversale Stabilität der synchronen Mannigfaltigkeit sind zentrale Eigenschaften. Erst seit einigen Jahren wird versucht, den verwickelten Zusammenhang zwischen der Kopplungsstruktur und den Stabilitätseigenschaften synchroner Zustände zu verstehen. Genau das ist das zentrale Thema dieser Arbeit. Zunächst präsentiere ich erste Ergebnisse zur Klassifizierung der Kanten eines gerichteten Netzwerks bezüglich ihrer Bedeutung für die Stabilität des synchronen Zustands. Folgend untersuche ich ein komplexes Verzweigungsszenario in einem gerichteten Ring von Stuart-Landau Oszillatoren und zeige, dass das Szenario persistent ist, wenn dem Netzwerk eine schwach gewichtete Kante hinzugefügt wird. Daraufhin untersuche ich synchrone Zustände in Ringen von Phasenoszillatoren die mit Zeitverzögerung gekoppelt sind. Ich bespreche die Koexistenz synchroner Lösungen und analysiere deren Stabilität und Verzweigungen. Weiter zeige ich, dass eine Zeitverschiebung genutzt werden kann, um Muster im Ring zu speichern und wiederzuerkennen. Diese Zeitverschiebung untersuche ich daraufhin für beliebige Kopplungsstrukturen. Ich zeige, dass invariante Mannigfaltigkeiten des Flusses sowie ihre Stabilität unter der Zeitverschiebung erhalten bleiben. Darüber hinaus bestimme ich die minimale Anzahl von Zeitverzögerungen, die gebraucht werden, um das System äquivalent zu beschreiben. Schließlich untersuche ich das auffällige Phänomen eines nichtstetigen Übergangs zu Synchronizität in Klassen großer Zufallsnetzwerke indem ich einen kürzlich eingeführten Zugang zur Beschreibung großer Zufallsnetzwerke auf den Fall zeitverzögerter Kopplungen verallgemeinere.Since a couple of decades, dynamics on networks is a rapidly growing branch of mathematics with applications in various disciplines such as physics, biology or sociology. The functioning of many networks heavily relies on the ability to synchronize the network’s nodes. More precisely, the existence and the transverse stability of the synchronous manifold are essential properties. It was only in the last few years that people tried to understand the entangled relation between the coupling structure of a network, given by a (di-)graph, and the stability properties of synchronous states. This is the central theme of this dissertation. I first present results towards a classification of the links in a directed, diffusive network according to their impact on the stability of synchronization. Then I investigate a complex bifurcation scenario observed in a directed ring of Stuart-Landau oscillators. I show that under the addition of a single weak link, this scenario is persistent. Subsequently, I investigate synchronous patterns in a directed ring of phase oscillators coupled with time delay. I discuss the coexistence of multiple of synchronous solutions and investigate their stability and bifurcations. I apply these results by showing that a certain time-shift transformation can be used in order to employ the ring as a pattern recognition device. Next, I investigate the same time-shift transformation for arbitrary coupling structures in a very general setting. I show that invariant manifolds of the flow together with their stability properties are conserved under the time-shift transformation. Furthermore, I determine the minimal number of delays needed to equivalently describe the system’s dynamics. Finally, I investigate a peculiar phenomenon of non-continuous transition to synchrony observed in certain classes of large random networks, generalizing a recently introduced approach for the description of large random networks to the case of delayed couplings

Complex and Adaptive Dynamical Systems: A Primer

An thorough introduction is given at an introductory level to the field of quantitative complex system science, with special emphasis on emergence in dynamical systems based on network topologies. Subjects treated include graph theory and small-world networks, a generic introduction to the concepts of dynamical system theory, random Boolean networks, cellular automata and self-organized criticality, the statistical modeling of Darwinian evolution, synchronization phenomena and an introduction to the theory of cognitive systems. It inludes chapter on Graph Theory and Small-World Networks, Chaos, Bifurcations and Diffusion, Complexity and Information Theory, Random Boolean Networks, Cellular Automata and Self-Organized Criticality, Darwinian evolution, Hypercycles and Game Theory, Synchronization Phenomena and Elements of Cognitive System Theory.Comment: unformatted version of the textbook; published in Springer, Complexity Series (2008, second edition 2010

The Kuramoto model in complex networks

181 pages, 48 figures. In Press, Accepted Manuscript, Physics Reports 2015 Acknowledgments We are indebted with B. Sonnenschein, E. R. dos Santos, P. Schultz, C. Grabow, M. Ha and C. Choi for insightful and helpful discussions. T.P. acknowledges FAPESP (No. 2012/22160-7 and No. 2015/02486-3) and IRTG 1740. P.J. thanks founding from the China Scholarship Council (CSC). F.A.R. acknowledges CNPq (Grant No. 305940/2010-4) and FAPESP (Grants No. 2011/50761-2 and No. 2013/26416-9) for financial support. J.K. would like to acknowledge IRTG 1740 (DFG and FAPESP).Peer reviewedPreprin

Feedback for neuronal system identification

In order to estimate reliable models from noisy input-output data, system identification techniques usually require that the data be generated by a process with a fading memory. Non-equilibrium systems such as neuronal and chaotic models lack a fading memory. Their identification is challenging, in particular in the presence of input noise. In this thesis, we propose a methodology based on the prediction-error method for the identification of neuronal systems subject to input-additive noise. We build on the fundamental observation that while a neuronal model does not have a fading memory, it can be transformed into a fading memory system by output feedback. Our ideas can be generalized to any non-equilibrium system sharing this property. At the core of the methodology is the use of output feedback in experiment design. We provide a theoretical justification for this design choice, which has been exploited in neurophysiology since the invention of the voltage-clamp experiment. To investigate the problem of feedback for identification, we first address the estimation of simple non-equilibrium systems in Lure form, and show that feedback allows estimating the nonlinearity in a static experiment. We then address the estimation of conductance-based models. Assuming that an informed choice can be made on the elements of the model structure, we show that consistent parameter estimates can be obtained when noise is only present at the system input. Finally, we approach the problem from a black-box perspective, and propose identifying the neuronal internal dynamics using a universal approximator with Generalized Orthogonal Basis Functions.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Brasil (Finance Code 001

A view of Neural Networks as dynamical systems

We consider neural networks from the point of view of dynamical systems theory. In this spirit we review recent results dealing with the following questions, adressed in the context of specific models. 1. Characterizing the collective dynamics; 2. Statistical analysis of spikes trains; 3. Interplay between dynamics and network structure; 4. Effects of synaptic plasticity.Comment: Review paper, 51 pages, 10 figures. submitte