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Modeling cell signal transduction pathways via Boolean networks (BNs) has become an established method for analyzing intracellular communications over the last few decades. What's more, BNs provide a course-grained approach, not only to understanding molecular communications, but also for targeting pathway components that alter the long-term outcomes of the system. This has come to be known as phenotype control theory. In this review we study the interplay of various approaches for controlling gene regulatory networks such as: algebraic methods, control kernel, feedback vertex set, and stable motifs. The study will also include comparative discussion between the methods, using an established cancer model of T-Cell Large Granular Lymphocyte Leukemia. Further, we explore possible options for making the control search more efficient using reduction and modularity. Finally, we will include challenges presented such as the complexity and the availability of software for implementing each of these control techniques.

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In this paper, four kinds of shadowing properties in non-autonomous discrete dynamical systems (NDDSs) are discussed. It is pointed out that if an NDDS has a F-shadowing property (resp. ergodic shadowing property, d¯ shadowing property, d̲ shadowing property), then the compound systems, conjugate systems, and product systems all have accordant shadowing properties. Moreover, the set-valued system (K(X),f¯1,∞) induced by the NDDS (X,f1,∞) has the above four shadowing properties, implying that the NDDS (X,f1,∞) has these properties.

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One of the main theoretical questions in the field of discrete regulatory networks is the question what aspects of the dynamics - the structure of the state transition graph - are already imposed by structural descriptions of the network such as the interaction graph. For Boolean networks, prior work has concentrated on different versions of the Thomas conjectures that link feedback cycles in the network structure to attractor properties. Other approaches check algorithmically whether certain properties hold true for all models sharing specific structural constraints, e.g. by using model checking techniques. In this work we investigate the behavior of the pool of Boolean networks in agreement with a given interaction graph using a different approach. Grouping together states that are updated consistently across the pool we derive an equivalence relation and analyze a corresponding quotient graph on the state space. By construction this graph yields information about the dynamics of all functions in the pool. Our main result is that this graph can be computed efficiently without enumerating and analyzing all individual functions. This opens up new possibilities for applications, where such model pools arise when modeling under uncertainty.

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The study of epidemics is useful for not only understanding outbreaks and trying to limit their adverse effects, but also because epidemics are related to social phenomena such as government instability, crime, poverty, and inequality. One approach for studying epidemics is to simulate their spread through populations. In this work, we describe an integrated multi-dimensional approach to epidemic simulation, which encompasses: (1) a theoretical framework for simulation and analysis; (2) synthetic population (digital twin) generation; (3) (social contact) network construction methods from synthetic populations, (4) stylized network construction methods; and (5) simulation of the evolution of a virus or disease through a social network. We describe these aspects and end with a short discussion on simulation results that inform public policy.

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Most studies of motifs of biological regulatory networks focus on the analysis of asymptotical behaviours (attractors, and even often only stable states), but transient properties are rarely addressed. In the line of our previous study devoted to isolated circuits (Remy et al. in Bioinformatics (Oxford, England) 19(Suppl. 2):172-178, 2003), we consider chorded circuits, that are motifs made of an elementary positive or negative circuit with a chord, possibly a self-loop. We provide detailed descriptions of the boolean dynamics of chorded circuits versus isolated circuits, under the synchronous and asynchronous updating schemes within the logical formalism. To this end, we address the description of the trajectories in the dynamics of isolated circuits with coding techniques and adapt them for chorded circuits. The use of the logical modeling gives access to mathematical tools (group actions, analysis of recurrent sequences, coding of trajectories, specific abacus...) allowing complete analytical analysis of basic yet important motifs. In particular, we show that whatever the chosen updating rule, the dynamics depends on a small number of parameters.

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Overpopulation and environmental degradation due to inadequate resource-use are outcomes of human's ecosystem engineering that has profoundly modified the world's landscape. Despite the age-old concern that unchecked population and economic growth may be unsustainable, the prospect of societal collapse remains contentious today. Contrasting with the usual approach to modeling human-nature interactions, which are based on the Lotka-Volterra predator-prey model with humans as the predators and nature as the prey, here we address this issue using a discrete-time population dynamics model of ecosystem engineers. The growth of the population of engineers is modeled by the Beverton-Holt equation with a density-dependent carrying capacity that is proportional to the number of usable habitats. These habitats (e.g., farms) are the products of the work of the individuals on the virgin habitats (e.g., native forests), hence the denomination engineers of ecosystems to those agents. The human-made habitats decay into degraded habitats, which eventually regenerate into virgin habitats. For slow regeneration resources, we find that the dynamics is dominated by rounds of prosperity and collapse, in which the population reaches vanishing small densities. However, increase of the efficiency of the engineers to explore the resources eliminates the dangerous oscillatory patterns of feast and famine and leads to a stable equilibrium that balances population growth and resource availability. This finding supports the viewpoint of growth optimists that technological progress may avoid collapse.

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Mental disorders like major depressive disorder can be modeled as complex dynamical systems. In this study we investigate the dynamic behavior of individuals to see whether or not we can expect a transition to another mood state. We introduce a mean field model to a binomial process, where we reduce a dynamic multidimensional system (stochastic cellular automaton) to a one-dimensional system to analyse the dynamics. Using maximum likelihood estimation, we can estimate the parameter of interest which, in combination with a bifurcation diagram, reflects the expectancy that someone has to transition to another mood state. After numerically illustrating the proposed method with simulated data, we apply this method to two empirical examples, where we show its use in a clinical sample consisting of patients diagnosed with major depressive disorder, and a general population sample. Results showed that the majority of the clinical sample was categorized as having an expectancy for a transition, while the majority of the general population sample did not have this expectancy. We conclude that the mean field model has great potential in assessing the expectancy for a transition between mood states. With some extensions it could, in the future, aid clinical therapists in the treatment of depressed patients.

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We present mathematical techniques for exhaustive studies of long-term dynamics of asynchronous biological system models. Specifically, we extend the notion of [Formula: see text]-equivalence developed for graph dynamical systems to support systematic analysis of all possible attractor configurations that can be generated when varying the asynchronous update order (Macauley and Mortveit in Nonlinearity 22(2):421, 2009). We extend earlier work by Veliz-Cuba and Stigler (J Comput Biol 18(6):783-794, 2011), Goles et al. (Bull Math Biol 75(6):939-966, 2013), and others by comparing long-term dynamics up to topological conjugation: rather than comparing the exact states and their transitions on attractors, we only compare the attractor structures. In general, obtaining this information is computationally intractable. Here, we adapt and apply combinatorial theory for dynamical systems from Macauley and Mortveit (Proc Am Math Soc 136(12):4157-4165, 2008. https://doi.org/10.1090/S0002-9939-09-09884-0 ; 2009; Electron J Comb 18:197, 2011a; Discret Contin Dyn Syst 4(6):1533-1541, 2011b. https://doi.org/10.3934/dcdss.2011.4.1533 ; Theor Comput Sci 504:26-37, 2013. https://doi.org/10.1016/j.tcs.2012.09.015 ; in: Isokawa T, Imai K, Matsui N, Peper F, Umeo H (eds) Cellular automata and discrete complex systems, 2014. https://doi.org/10.1007/978-3-319-18812-6_6 ) to develop computational methods that greatly reduce this computational cost. We give a detailed algorithm and apply it to (i) the lac operon model for Escherichia coli proposed by Veliz-Cuba and Stigler (2011), and (ii) the regulatory network involved in the control of the cell cycle and cell differentiation in the Caenorhabditis elegans vulva precursor cells proposed by Weinstein et al. (BMC Bioinform 16(1):1, 2015). In both cases, we uncover all possible limit cycle structures for these networks under sequential updates. Specifically, for the lac operon model, rather than examining all [Formula: see text] sequential update orders, we demonstrate that it is sufficient to consider 344 representative update orders, and, more notably, that these 344 representatives give rise to 4 distinct attractor structures. A similar analysis performed for the C. elegans model demonstrates that it has precisely 125 distinct attractor structures. We conclude with observations on the variety and distribution of the models' attractor structures and use the results to discuss their robustness.

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This article uses a recently presented abstract, tunable Boolean regulatory network model to further explore aspects of mobile DNA, such as transposons. The significant role of mobile DNA in the evolution of natural systems is becoming increasingly clear. This article shows how dynamically controlling network node connectivity and function via transposon-inspired mechanisms can be selected for to significant degrees under coupled regulatory network scenarios, including when such changes are heritable. Simple multicellular and coevolutionary versions of the model are considered.

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