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Effect of memory in non-Markovian Boolean networks

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 Added by Haleh Ebadi
 Publication date 2016
  fields Biology Physics
and research's language is English




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One successful model of interacting biological systems is the Boolean network. The dynamics of a Boolean network, controlled with Boolean functions, is usually considered to be a Markovian (memory-less) process. However, both self organizing features of biological phenomena and their intelligent nature should raise some doubt about ignoring the history of their time evolution. Here, we extend the Boolean network Markovian approach: we involve the effect of memory on the dynamics. This can be explored by modifying Boolean functions into non-Markovian functions, for example, by investigating the usual non-Markovian threshold function, - one of the most applied Boolean functions. By applying the non-Markovian threshold function on the dynamical process of a cell cycle network, we discover a power law memory with a more robust dynamics than the Markovian dynamics.



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We study the stable attractors of a class of continuous dynamical systems that may be idealized as networks of Boolean elements, with the goal of determining which Boolean attractors, if any, are good approximations of the attractors of generic continuous systems. We investigate the dynamics in simple rings and rings with one additional self-input. An analysis of switching characteristics and pulse propagation explains the relation between attractors of the continuous systems and their Boolean approximations. For simple rings, reliable Boolean attractors correspond to stable continuous attractors. For networks with more complex logic, the qualitative features of continuous attractors are influenced by inherently non-Boolean characteristics of switching events.
Despite their topological complexity almost all functional properties of metabolic networks can be derived from steady-state dynamics. Indeed, many theoretical investigations (like flux-balance analysis) rely on extracting function from steady states. This leads to the interesting question, how metabolic networks avoid complex dynamics and maintain a steady-state behavior. Here, we expose metabolic network topologies to binary dynamics generated by simple local rules. We find that the networks response is highly specific: Complex dynamics are systematically reduced on metabolic networks compared to randomized networks with identical degree sequences. Already small topological modifications substantially enhance the capacity of a network to host complex dynamic behavior and thus reduce its regularizing potential. This exceptionally pronounced regularization of dynamics encoded in the topology may explain, why steady-state behavior is ubiquitous in metabolism.
Complex systems are often modeled as Boolean networks in attempts to capture their logical structure and reveal its dynamical consequences. Approximating the dynamics of continuous variables by discrete values and Boolean logic gates may, however, introduce dynamical possibilities that are not accessible to the original system. We show that large random networks of variables coupled through continuous transfer functions often fail to exhibit the complex dynamics of corresponding Boolean models in the disordered (chaotic) regime, even when each individual function appears to be a good candidate for Boolean idealization. A suitably modified Boolean theory explains the behavior of systems in which information does not propagate faithfully down certain chains of nodes. Model networks incorporating calculated or directly measured transfer functions reported in the literature on transcriptional regulation of genes are described by the modified theory.
Boolean networks are discrete dynamical systems for modeling regulation and signaling in living cells. We investigate a particular class of Boolean functions with inhibiting inputs exerting a veto (forced zero) on the output. We give analytical expressions for the sensitivity of these functions and provide evidence for their role in natural systems. In an intracellular signal transduction network [Helikar et al., PNAS (2008)], the functions with veto are over-represented by a factor exceeding the over-representation of threshold functions and canalyzing functions in the same system. In Boolean networks for control of the yeast cell cycle [Fangting Li et al., PNAS (2004), Davidich et al., PLoS One (2009)], none or minimal changes to the wiring diagrams are necessary to formulate their dynamics in terms of the veto functions introduced here.
In a recent paper [C. Marr, M. Mueller-Linow, and M.-T. Huett, Phys. Rev. E 75, 041917 (2007)] we discuss the pronounced potential of real metabolic network topologies, compared to randomized counterparts, to regularize complex binary dynamics. In their comment [P. Holme and M. Huss, arXiv:0705.4084v1], Holme and Huss criticize our approach and repeat our study with more realistic dynamics, where stylized reaction kinetics are implemented on sets of pairwise reactions. The authors find no dynamic difference between the reaction sets recreated from the metabolic networks and randomized counterparts. We reproduce the authors observation and find that their algorithm leads to a dynamical fragmentation and thus eliminates the topological information contained in the graphs. Hence, their approach cannot rule out a connection between the topology of metabolic networks and the ubiquity of steady states.
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