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Publications about 'genetic regulatory'
Articles in journal or book chapters
  1. M. Chaves, E.D. Sontag, and R. Albert. Methods of robustness analysis for Boolean models of gene control networks. IET Systems Biology, 153:154-167, 2006. [PDF] Keyword(s): systems biology, biochemical networks, boolean systems, gene and protein networks, hybrid systems.
    Abstract:
    As a discrete approach to genetic regulatory networks, Boolean models provide an essential qualitative description of the structure of interactions among genes and proteins. Boolean models generally assume only two possible states (expressed or not expressed) for each gene or protein in the network as well as a high level of synchronization among the various regulatory processes. In this paper, we discuss and compare two possible methods of adapting qualitative models to incorporate the continuous-time character of regulatory networks. The first method consists of introducing asynchronous updates in the Boolean model. In the second method, we adopt the approach introduced by L. Glass to obtain a set of piecewise linear differential equations which continuously describe the states of each gene or protein in the network. We apply both methods to a particular example: a Boolean model of the segment polarity gene network of Drosophila melanogaster. We analyze the dynamics of the model, and provide a theoretical characterization of the model's gene pattern prediction as a function of the timescales of the various processes.


  2. M. Chaves, R. Albert, and E.D. Sontag. Robustness and fragility of Boolean models for genetic regulatory networks. J. Theoret. Biol., 235(3):431-449, 2005. [PDF] Keyword(s): systems biology, biochemical networks, boolean systems, gene and protein networks.
    Abstract:
    Interactions between genes and gene products give rise to complex circuits that enable cells to process information and respond to external signals. Theoretical studies often describe these interactions using continuous, stochastic, or logical approaches. Here we propose a framework for gene regulatory networks that combines the intuitive appeal of a qualitative description of gene states with a high flexibility in incorporating stochasticity in the duration of cellular processes. We apply our methods to the regulatory network of the segment polarity genes, thus gaining novel insights into the development of gene expression patterns. For example, we show that very short synthesis and decay times can perturb the wild type pattern. On the other hand, separation of timescales between pre- and post-translational processes and a minimal prepattern ensure convergence to the wild type expression pattern regardless of fluctuations.


Conference articles
  1. N.S. Kumar, M. A. Al-Radhawi, D. Del Vecchio, and E. D. Sontag. Stochasticity is necessary for multiple attractors in a class of differentiation networks. In 2017 American Control Conference (ACC), pages submitted, 2017. Keyword(s): systems biology, genetic regulatory, multistability, gene networks.
    Abstract:
    Deterministic models remain the most common option for modeling gene regulatory networks even when the underlying assumptions of high copy numbers and fast promoter kinetics are unsatisfied. Here, we analyze a widely studied differentiation network motif known as the PU.1-GATA-1 circuit and we show that an ODE model of the biomolecular reactions consistent with known biology is incapable of exhibiting multistability, a defining behaviour for such a network. Thus, we consider the chemical master equation model of the same biomolecular reactions and using results recently developed by the authors, we analytically construct the stationary distribution. We show that this distribution is indeed capable of admitting a multitude of modes. We illustrate the results with a numerical example.


  2. Q. Tyles, T. Kang, E.D. Sontag, and L. Bleris. Exploring the impact of resource limitations on gene network reconstruction. In Proc. IEEE Conf. Decision and Control, Dec. 2016, pages 3350-3355, 2016. [PDF] Keyword(s): Biological systems, Genetic regulatory systems, Systems biology.
    Abstract:
    Applying Modular Response Analysis to a synthetic gene circuit, which was introduced in a recent paper by the authors, leads to the inference of a nontrivial "ghost" regulation edge which was not explicitly engineered into the network and which is, in fact, not immediately apparent from experimental measurements. One may thus hypothesize that this ghost regulatory effect is due to competition for resources. A mathematical model is proposed, and analyzed in closed form, that lends validation to this hypothesis.


  3. M. Chaves, E.D. Sontag, and R. Albert. Structure and timescale analysis in genetic regulatory networks. In Proc. IEEE Conf. Decision and Control, San Diego, Dec. 2006, pages 2358-2363, 2006. IEEE. [PDF] Keyword(s): genetic regulatory networks, Boolean systems, hybrid systems.
    Abstract:
    This work is concerned with the study of the robustness and fragility of gene regulation networks to variability in the timescales of the distinct biological processes involved. It explores and compares two methods: introducing asynchronous updates in a Boolean model, or integrating the Boolean rules in a continuous, piecewise linear model. As an example, the segment polarity network of the fruit fly is analyzed. A theoretical characterization is given of the model's ability to predict the correct development of the segmented embryo, in terms of the specific timescales of the various regulation interactions.



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