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Publications about 'adaptation'
Articles in journal or book chapters
  1. S. J. Rahi, J. Larsch, K. Pecani, N. Mansouri, A. Y. Katsov, K. Tsaneva-Atanasova, E. D. Sontag, and F. R. Cross. Oscillatory stimuli differentiate adapting circuit topologies. Nature Methods, 14:1010-1016, 2017. [PDF] Keyword(s): biochemical networks, periodic behaviors, monotone systems, entrainment, oscillations.
    Abstract:
    Elucidating the structure of biological intracellular networks from experimental data remains a major challenge. This paper studies two types of ``response signatures'' to identify specific circuit motifs, from the observed response to periodic inputs. In particular, the objective is to distinguish negative feedback loops (NFLs) from incoherent feedforward loops (IFFLs), which are two types of circuits capable of producing exact adaptation. The theory of monotone systems with inputs is used to show that ``period skipping'' (non-harmonic responses) is ruled out in IFFL's, and a notion called ``refractory period stabilization'' is also analyzed. The approach is then applied to identify a circuit dominating cell cycle timing in yeast, and to uncover a calcium-mediated NFL circuit in \emph{C.elegans} olfactory sensory neurons.


  2. A.O. Hamadeh, B.P. Ingalls, and E.D. Sontag. Transient dynamic phenotypes as criteria for model discrimination: fold-change detection in Rhodobacter sphaeroides chemotaxis. Proc. Royal Society Interface, 10:20120935, 2013. [PDF] Keyword(s): scale invariance, systems biology, transient behavior, symmetries, fcd, fold-change detection, chemotaxis.
    Abstract:
    The chemotaxis pathway of the bacterium Rhodobacter sphaeroides has many similarities to that of Escherichia coli. It exhibits robust adaptation and has several homologues of the latter's chemotaxis proteins. Recent theoretical results have correctly predicted that, in response to a scaling of its ligand input signal, Escherichia coli exhibits the same output behavior, a property known as fold-change detection (FCD). In light of recent experimental results suggesting that R. sphaeroides may also show FCD, we present theoretical assumptions on the R. sphaeroides chemosensory dynamics that can be shown to yield FCD behavior. Furthermore, it is shown that these assumptions make FCD a property of this system that is robust to structural and parametric variations in the chemotaxis pathway, in agreement with experimental results. We construct and examine models of the full chemotaxis pathway that satisfy these assumptions and reproduce experimental time-series data from earlier studies. We then propose experiments in which models satisfying our theoretical assumptions predict robust FCD behavior where earlier models do not. In this way, we illustrate how transient dynamic phenotypes such as FCD can be used for the purposes of discriminating between models that reproduce the same experimental time-series data.


  3. L. Bleris, Z. Xie, D. Glass, A. Adadey, E.D. Sontag, and Y. Benenson. Synthetic incoherent feed-forward circuits show adaptation to the amount of their genetic template. Molecular Systems Biology, 7:519-, 2011. [PDF] Keyword(s): adaptation, feedforward loops, systems biology, synthetic biology.
    Abstract:
    Natural and synthetic biological networks must function reliably in the face of fluctuating stoichiometry of their molecular components. These fluctuations are caused in part by changes in relative expression efficiency and the DNA template amount of the network-coding genes. Gene product levels could potentially be decoupled from these changes via built-in adaptation mechanisms, thereby boosting network reliability. Here we show that a mechanism based on an incoherent feed-forward motif enables adaptive gene expression in mammalian cells. We modeled, synthesized, and tested transcriptional and post-transcriptional incoherent loops and found that in all cases the gene product adapts to changes in DNA template abundance. We also observed that the post-transcriptional form results in superior adaptation behavior, higher absolute expression levels, and lower intrinsic fluctuations. Our results support a previously-hypothesized endogenous role in gene dosage compensation for such motifs and suggest that their incorporation in synthetic networks will improve their robustness and reliability.


  4. O. Shoval, U. Alon, and E.D. Sontag. Symmetry invariance for adapting biological systems. SIAM Journal on Applied Dynamical Systems, 10:857-886, 2011. Note: See here for a small typo: http://www.math.rutgers.edu/(tilde)sontag/FTPDIR/shoval.alon.sontag.erratum.pdf.[PDF] Keyword(s): adaptation, feedforward loops, integral feedback, scale invariance, systems biology, transient behavior, symmetries, fcd, fold-change detection.
    Abstract:
    Often, the ultimate goal of regulation is to maintain a narrow range of concentration levels of vital quantities (homeostasis, adaptation) while at the same time appropriately reacting to changes in the environment (signal detection or sensitivity). Much theoretical, modeling, and analysis effort has been devoted to the understanding of these questions, traditionally in the context of steady-state responses to constant or step-changing stimuli. In this paper, we present a new theorem that provides a necessary and sufficient characterization of invariance of transient responses to symmetries in inputs. A particular example of this property, scale invariance (a.k.a. "fold change detection"), appears to be exhibited by biological sensory systems ranging from bacterial chemotaxis pathways to signal transduction mechanisms in eukaryotes. The new characterization amounts to the solvability of an associated partial differential equation. It is framed in terms of a notion which considerably extends equivariant actions of compact Lie groups. For several simple system motifs that are recurrent in biology, the solvability criterion may be checked explicitly.


  5. O. Shoval, L. Goentoro, Y. Hart, A. Mayo, E.D. Sontag, and U. Alon. Fold change detection and scalar symmetry of sensory input fields. Proc Natl Acad Sci USA, 107:15995-16000, 2010. [PDF] Keyword(s): adaptation, feedforward loops, integral feedback, scale invariance, systems biology, transient behavior, symmetries, fcd, fold-change detection.
    Abstract:
    Certain cellular sensory systems display fold-change detection (FCD): a response whose entire shape, including amplitude and duration, depends only on fold-changes in input, and not on absolute changes. Thus, a step change in input from, say, level 1 to 2, gives precisely the same dynamical output as a step from level 2 to 4, since the steps have the same fold-change. We ask what is the benefit of FCD, and show that FCD is necessary and sufficient for sensory search to be independent of multiplying the input-field by a scalar. Thus the FCD search pattern depends only on the spatial profile of the input, and not on its amplitude. Such scalar symmetry occurs in a wide range of sensory inputs, such as source strength multiplying diffusing/convecting chemical fields sensed in chemotaxis, ambient light multiplying the contrast field in vision, and protein concentrations multiplying the output in cellular signaling-systems.Furthermore, we demonstrate that FCD entails two features found across sensory systems, exact adaptation and Weber's law, but that these two features are not sufficient for FCD. Finally, we present a wide class of mechanisms that have FCD, including certain non-linear feedback and feedforward loops.. We find that bacterial chemotaxis displays feedback within the present class, and hence is expected to show FCD. This can explain experiments in which chemotaxis searches are insensitive to attractant source levels. This study thus suggests a connection between properties of biological sensory systems and scalar symmetry stemming from physical properties of their input-fields.


  6. E.D. Sontag. Remarks on Feedforward Circuits, Adaptation, and Pulse Memory. IET Systems Biology, 4:39-51, 2010. [PDF] Keyword(s): adaptation, feedforward loops, integral feedback, systems biology, transient behavior.
    Abstract:
    This note studies feedforward circuits as models for perfect adaptation to step signals in biological systems. A global convergence theorem is proved in a general framework, which includes examples from the literature as particular cases. A notable aspect of these circuits is that they do not adapt to pulse signals, because they display a memory phenomenon. Estimates are given of the magnitude of this effect.


  7. L. Wang and E.D. Sontag. Singularly perturbed monotone systems and an application to double phosphorylation cycles. J. Nonlinear Science, 18:527-550, 2008. [PDF] Keyword(s): singular perturbations, futile cycles, MAPK cascades, systems biology, biochemical networks, nonlinear stability, nonlinear dynamics, multistability, monotone systems.
    Abstract:
    The theory of monotone dynamical systems has been found very useful in the modeling of some gene, protein, and signaling networks. In monotone systems, every net feedback loop is positive. On the other hand, negative feedback loops are important features of many systems, since they are required for adaptation and precision. This paper shows that, provided that these negative loops act at a comparatively fast time scale, the main dynamical property of (strongly) monotone systems, convergence to steady states, is still valid. An application is worked out to a double-phosphorylation "futile cycle" motif which plays a central role in eukaryotic cell signaling.


  8. T. Gedeon and E.D. Sontag. Oscillations in multi-stable monotone systems with slowly varying feedback. J. of Differential Equations, 239:273-295, 2007. [PDF] Keyword(s): systems biology, biochemical networks, nonlinear stability, dynamical systems, monotone systems.
    Abstract:
    This paper gives a theorem showing that a slow feedback adaptation, acting entirely analogously to the role of negative feedback for ordinary relaxation oscillations, leads to periodic orbits for bistable monotone systems. The proof is based upon a combination of i/o monotone systems theory and Conley Index theory.


  9. L. Moreau and E.D. Sontag. Balancing at the border of instability. Phys. Rev. E (3), 68(2):020901, 4, 2003. [PDF] Keyword(s): bifurcations, adaptive control.
    Abstract:
    Some biological systems operate at the critical point between stability and instability and this requires a fine-tuning of parameters. We bring together two examples from the literature that illustrate this: neural integration in the nervous system and hair cell oscillations in the auditory system. In both examples the question arises as to how the required fine-tuning may be achieved and maintained in a robust and reliable way. We study this question using tools from nonlinear and adaptive control theory. We illustrate our approach on a simple model which captures some of the essential features of neural integration. As a result, we propose a large class of feedback adaptation rules that may be responsible for the experimentally observed robustness of neural integration. We mention extensions of our approach to the case of hair cell oscillations in the ear.


  10. E.D. Sontag. Adaptation and regulation with signal detection implies internal model. Systems Control Lett., 50(2):119-126, 2003. [PDF] Keyword(s): biological adaptation, internal model principle.
    Abstract:
    This note provides a simple result showing, under suitable technical assumptions, that if a system S adapts to a class of external signals U, then S must necessarily contain a subsystem which is capable of generating all the signals in U. It is not assumed that regulation is robust, nor is there a prior requirement for the system to be partitioned into separate plant and controller components. Instead, a "signal detection" capability is imposed. These weaker assumptions make the result better applicable to cellular phenomena such as the adaptation of E-coli chemotactic tumbling rate to constant concentrations.


Conference articles
  1. M. Skataric, E.V. Nikolaev, and E.D. Sontag. Scale-invariance in singularly perturbed systems. In Proc. IEEE Conf. Decision and Control, Los Angeles, Dec. 2014, pages 3035-3040, 2014. [PDF] Keyword(s): singular perturbations, scale invariance, systems biology, transient behavior, symmetries, fcd, fold-change detection.
    Abstract:
    This conference paper (a) summarizes material from "A fundamental limitation to fold-change detection by biological systems with multiple time scales" (IET Systems Biology 2014) and presents additional remarks regarding (b) expansion techniques to compute FCD error and (c) stochastic adaptation and FCD


  2. O. Shoval, U. Alon, and E.D. Sontag. Input symmetry invariance, and applications to biological systems. In Proc. IEEE Conf. Decision and Control, Orlando, Dec. 2011, pages TuA02.5, 2011. Keyword(s): adaptation, feedforward loops, integral feedback, scale invariance, systems biology, transient behavior, symmetries, fcd, fold-change detection, jump Markov processes.
    Abstract:
    This paper studies invariance with respect to symmetries in sensory fields, a particular case of which, scale invariance, has recently been found in certain eukaryotic as well as bacterial cell signaling systems. We describe a necessary and sufficient characterization of symmetry invariance in terms of equivariant transformations, show how this characterization helps find all possible symmetries in standard models of biological adaptation, and discuss symmetry-invariant searches.


  3. B. Andrews, E.D. Sontag, and P. Iglesias. An approximate internal model principle: Applications to nonlinear models of biological systems. In Proc. 17th IFAC World Congress, Seoul, pages Paper FrB25.3, 6 pages, 2008. [PDF] Keyword(s): biological adaptation, internal model principle.
    Abstract:
    The proper function of many biological systems requires that external perturbations be detected, allowing the system to adapt to these environmental changes. It is now well established that this dual detection and adaptation requires that the system have an internal model in the feedback loop. In this paper we relax the requirement that the response of the system adapt perfectly, but instead allow regulation to within a neighborhood of zero. We show, in a nonlinear setting, that systems with the ability to detect input signals and approximately adapt require an approximate model of the input. We illustrate our results by analyzing a well-studied biological system. These results generalize previous work which treats the perfectly adapting case.


  4. B. Andrews, P. Iglesias, and E.D. Sontag. Signal detection and approximate adaptation implies an approximate internal model. In Proc. IEEE Conf. Decision and Control, San Diego, Dec. 2006, pages 2364-2369, 2006. IEEE. [PDF] Keyword(s): biological adaptation, internal model principle.
    Abstract:
    This conference paper presented a version of an approximate internal model principle, for linear systems. A subsequent paper at the IFAC 2008 conference improved on this result by extending it to a class of nonlinear systems.



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Last modified: Thu Nov 23 10:40:56 2017
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