Comparing the evolution of canalyzing and threshold networks

We study the influence of the type of update functions on the evolution of Boolean networks under selection for dynamical robustness. The chosen types of functions are canalyzing functions and threshold functions. Starting from a random initial network, we evolve the network by an adaptive walk. During the first time period, where the networks evolve to the plateau of 100 percent fitness, we find that both type of update functions give the same behavior, albeit for different network sizes and connectedness. However, on the long run, as the networks continue to evolve on the fitness plateau, the different types of update functions give rise to different network structure, due to their different mutational robustness. When both types of update functions occur together, none of them is preferred under long-term evolution.     

Statistical evidence of strain induced breaking of metallic point contacts

As a paradigm for modeling gene regulatory networks, probabilistic Boolean networks (PBNs) form a subclass of Markov genetic regulatory networks. To date, many different stochastic optimal control approaches have been developed to find therapeutic intervention strategies for PBNs. A PBN is essentially a collection of constituent Boolean networks via a probability structure. Most of the existing works assume that the probability structure for Boolean networks selection is known. Such an assumption cannot be satisfied in practice since the presence of noise prevents the probability structure from being accurately determined. In this paper, we treat a case in which we lack the governing probability structure for Boolean network selection. Specifically, in the framework of PBNs, the theory of finite horizon Markov decision process is employed to find optimal constituent Boolean networks with respect to the defined objective functions. In order to illustrate the validity of our proposed approach, an example is also displayed.     

Kauffman networks with threshold functions

We investigate Threshold Random Boolean Networks with K = 2 inputs per node, which are equivalent to Kauffman networks, with only part of the canalyzing functions as update functions. According to the simplest consideration these networks should be critical but it turns out that they show a rich variety of behaviors, including periodic and chaotic oscillations. The analytical results are supported by computer simulations.     

Stability of functions in Boolean models of gene regulatory networks

Boolean networks are used to model large nonlinear systems such as gene regulatory networks. We will present results that can be used to understand how the choice of functions affects the network dynamics. The so called bias-map and its fixed points depict much of the function's dynamical role in the network. We define the concept of stabilizing functions and show that many Post and canalizing functions are also stabilizing functions. Boolean networks constructed using the same type of stabilizing functions are always stable regardless of the average in-degree of network functions. We derive the number of all stabilizing functions and find it to be much larger than the number of Post and canalizing functions. We also discuss the implementation of functions and apply the presented results to biological data that give an approximation of the distribution of regulatory functions in eucaryotic cells. We find that the obtained theoretical results on the number of active genes are biologically plausible. Finally, based on the presented results, we discuss why canalizing and Post regulatory functions seem to be common in cells.     

Evolution of canalizing Boolean networks

Boolean networks with canalizing functions are used to model gene regulatory networks. In order to learn how such networks may behave under evolutionary forces, we simulate the evolution of a single Boolean network by means of an adaptive walk, which allows us to explore the fitness landscape. Mutations change the connections and the functions of the nodes. Our fitness criterion is the robustness of the dynamical attractors against small perturbations. We find that with this fitness criterion the global maximum is always reached and that there is a huge neutral space of 100% fitness. Furthermore, in spite of having such a high degree of robustness, the evolved networks still share many features with “chaotic” networks.     

Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function

Living cells can maintain their internal states, react to changing environments, grow, differentiate, divide, etc. All these processes are tightly controlled by what can be called a regulatory program. The logic of the underlying control can sometimes be guessed at by examining the network of influences amongst genetic components. Some associated gene regulatory networks have been studied in prokaryotes and eukaryotes, unveiling various structural features ranging from broad distributions of out-degrees to recurrent “motifs”, that is small subgraphs having a specific pattern of interactions. To understand what factors may be driving such structuring, a number of groups have introduced frameworks to model the dynamics of gene regulatory networks. In that context, we review here such in silico approaches and show how selection for phenotypes, i.e., network function, can shape network structure.     

The phase diagram of random Boolean networks with nested canalizing functions

We obtain the phase diagram of random Boolean networks with nested canalizing functions. Using the annealed approximation, we obtain the evolution of the number b _t of nodes with value one, and the network sensitivity λ, and compare with numerical simulations of quenched networks. We find that, contrary to what was reported by Kauffman et al. [Proc. Natl. Acad. Sci. 101, 17102 (2004)], these networks have a rich phase diagram, were both the “chaotic" and frozen phases are present, as well as an oscillatory regime of the value of b _t . We argue that the presence of only the frozen phase in the work of Kauffman et al. was due simply to the specific parametrization used, and is not an inherent feature of this class of functions. However, these networks are significantly more stable than the variant where all possible Boolean functions are allowed.     

An adjustable aperiodic model class of genomic interactions using continuous time Boolean networks (Boolean delay equations)

Following the complete sequencing of several genomes, interest has grown in the construction of genetic regulatory networks, which attempt to describe how different genes work together in both normal and abnormal cells. This interest has led to significant research in the behavior of abstract network models, with Boolean networks emerging as one particularly popular type. An important limitation of these networks is that their time evolution is necessarily periodic, motivating our interest in alternatives that are capable of a wider range of dynamic behavior. In this paper we examine one such class, that of continuous-time Boolean networks, a special case of the class of Boolean delay equations (BDEs) proposed for climatic and seismological modeling. In particular, we incorporate a biologically motivated refractory period into the dynamic behavior of these networks, which exhibit binary values like traditional Boolean networks, but which, unlike Boolean networks, evolve in continuous time. In this way, we are able to overcome both computational and theoretical limitations of the general class of BDEs while still achieving dynamics that are either aperiodic or effectively so, with periods many orders of magnitude longer than those of even large discrete time Boolean networks.     

Topological origin of global attractors in gene regulatory networks

Fixed-point attractors with global stability manifest themselves in a number of gene regulatory networks. This property indicates the stability of regulatory networks against small state perturbations and is closely related to other complex dynamics. In this paper, we aim to reveal the core modules in regulatory networks that determine their global attractors and the relationship between these core modules and other motifs. This work has been done via three steps. Firstly, inspired by the signal transmission in the regulation process, we extract the model of chain-like network from regulation networks. We propose a module of “ideal transmission chain(ITC)”, which is proved sufficient and necessary(under certain condition) to form a global fixed-point in the context of chain-like network. Secondly, by examining two well-studied regulatory networks(i.e., the cell-cycle regulatory networks of Budding yeast and Fission yeast), we identify the ideal modules in true regulation networks and demonstrate that the modules have a superior contribution to network stability(quantified by the relative size of the biggest attraction basin). Thirdly, in these two regulation networks, we find that the double negative feedback loops, which are the key motifs of forming bistability in regulation, are connected to these core modules with high network stability. These results have shed new light on the connection between the topological feature and the dynamic property of regulatory networks.     

Canalizing Kauffman networks: nonergodicity and its effect on their critical behavior

Boolean networks have been used to study numerous phenomena, including gene regulation, neural networks, social interactions, and biological evolution. Here, we propose a general method for determining the critical behavior of Boolean systems built from arbitrary ensembles of Boolean functions. In particular, we solve the critical condition for systems of units operating according to canalizing functions and present strong numerical evidence that our approach correctly predicts the phase transition from order to chaos in such systems.     

Dynamical response to perturbation of critical Boolean networks

Boolean networks can be used as simple but general models for complex self-organizing systems. The freedom to choose different rules and structures of interactions makes this model applicable to a wide variety of complex phenomena. It is known that the damage dynamics in annealed Boolean systems should fall in the same universality class of the directed percolation model. In this work we present results about the behavior of this model at and near the critically ordered condition for both the annealed and the quenched versions of the model. Our study concentrates on the way the system responds to a small perturbation. We show that the characteristic correlation time, i.e., the time in which any memory of this perturbation is lost, diverges as one moves towards criticality. Exactly at the critical point, we observe that the time for returning to the natural state after the perturbation follows a power-law distribution. This indicates that most perturbations are quickly restored, while few events may have a global effect on the system, suggesting a mechanism that assures at the same time robustness and adaptability. The critical exponents obtained are in agreement with the values expected for the universality class of mean-field directed percolation both in the annealed and in the quenched Boolean network model. This gives further evidence that annealed Boolean networks may in certain conditions provide a good model for understanding the behavior of regulatory systems. Our results may give insight into the way real self-organizing systems respond to external stimuli, and why critically ordered systems are often observed in Nature.     

Coevolution of information processing and topology in hierarchical adaptive random Boolean networks

Random Boolean Networks (RBNs) are frequently used for modeling complex systems driven by information processing, e.g. for gene regulatory networks (GRNs). Here we propose a hierarchical adaptive random Boolean Network (HARBN) as a system consisting of distinct adaptive RBNs (ARBNs) – subnetworks – connected by a set of permanent interlinks. We investigate mean node information, mean edge information as well as mean node degree. Information measures and internal subnetworks topology of HARBN coevolve and reach steady-states that are specific for a given network structure. The main natural feature of ARBNs, i.e. their adaptability, is preserved in HARBNs and they evolve towards critical configurations which is documented by power law distributions of network attractor lengths. The mean information processed by a single node or a single link increases with the number of interlinks added to the system. The mean length of network attractors and the mean steady-state connectivity possess minima for certain specific values of the quotient between the density of interlinks and the density of all links in networks. It means that the modular network displays extremal values of its observables when subnetworks are connected with a density a few times lower than a mean density of all links.     

Chaotic Dynamics in an Electronic Model of a Genetic Network

We consider dynamics in a class of piecewise-linear ordinary differential equations and in an electronic circuit that model genetic networks. In these models, gene activity varies continuously in time. However, as in Boolean or discrete-time switching networks, gene activity is driven high or low based only on whether the activities of the regulating genes are high or low (i.e., above or below certain thresholds). Depending on the “regulatory logic”, these models can exhibit simple dynamics, like stable fixed points or oscillation, or chaotic dynamics. The observed qualitative and quantitative differences between the dynamics in the idealized equations and the dynamics in the electronic circuit lead us to focus attention on the analysis of the dynamics as a function of parameter values. We propose new techniques for solving the inverse problem – the problem of inferring the regulatory logic and parameters from time series data. We also give new symbolic and statistical methods for characterizing dynamics in these networks.     

Superpolynomial growth in the number of attractors in Kauffman networks

The Kauffman model describes a particularly simple class of random Boolean networks. Despite the simplicity of the model, it exhibits complex behavior and has been suggested as a model for real world network problems. We introduce a novel approach to analyzing attractors in random Boolean networks, and applying it to Kauffman networks we prove that the average number of attractors grows faster than any power law with system size.     

Scaling in ordered and critical random boolean networks

Random Boolean networks, originally invented as models of genetic regulatory networks, are simple models for a broad class of complex systems that show rich dynamical structures. From a biological perspective, the most interesting networks lie at or near a critical point in parameter space that divides "ordered" from "chaotic" attractor dynamics. We study the scaling of the average number of dynamically relevant nodes and the median number of distinct attractors in such networks. Our calculations indicate that the correct asymptotic scalings emerge only for very large systems.     

Gauss–Manin Connection in Disguise: Calabi–Yau Threefolds

We describe a Lie Algebra on the moduli space of non-rigid compact Calabi–Yau threefolds enhanced with differential forms and its relation to the Bershadsky–Cecotti–Ooguri–Vafa holomorphic anomaly equation. In particular, we describe algebraic topological string partition functions \({{\bf F}_{g}^{\rm alg}, g \geq 1}\), which encode the polynomial structure of holomorphic and non-holomorphic topological string partition functions. Our approach is based on Grothendieck’s algebraic de Rham cohomology and on the algebraic Gauss–Manin connection. In this way, we recover a result of Yamaguchi–Yau and Alim–Länge in an algebraic context. Our proofs use the fact that the special polynomial generators defined using the special geometry of deformation spaces of Calabi–Yau threefolds correspond to coordinates on such a moduli space. We discuss the mirror quintic as an example.     

Propagation of external regulation and asynchronous dynamics in random Boolean networks

Boolean networks and their dynamics are of great interest as abstract modeling schemes in various disciplines, ranging from biology to computer science. Whereas parallel update schemes have been studied extensively in past years, the level of understanding of asynchronous updates schemes is still very poor. In this paper we study the propagation of external information given by regulatory input variables into a random Boolean network. We compute both analytically and numerically the time evolution and the asymptotic behavior of this propagation of external regulation (PER). In particular, this allows us to identify variables that are completely determined by this external information. All those variables in the network that are not directly fixed by PER form a core which contains, in particular, all nontrivial feedback loops. We design a message-passing approach allowing to characterize the statistical properties of these cores in dependence of the Boolean network and the external condition. At the end we establish a link between PER dynamics and the full random asynchronous dynamics of a Boolean network.     

Statistical analysis of gene regulatory networks reconstructed from gene expression data of lung cancer

Recently, inferring gene regulatory network from large-scale gene expression data has been considered as an important effort to understand the life system in whole. In this paper, for the purpose of getting further information about lung cancer, a gene regulatory network of lung cancer is reconstructed from gene expression data. In this network, vertices represent genes and edges between any two vertices represent their co-regulatory relationships. It is found that this network has some characteristics which are shared by most cellular networks of health lives, such as power-law, small-world behaviors. On the other hand, it also presents some features which are obviously different from other networks, such as assortative mixing. In the last section of this paper, the significance of these findings in the context of biological processes of lung cancer is discussed.     

Core percolation and onset of complexity in boolean networks

The determination and classification of fixed points of large Boolean networks is addressed in terms of a constraint-satisfaction problem. We develop a general simplification scheme that, removing all those variables and functions belonging to trivial logical cascades, returns the computational core of the network. The transition line from an easy to a complex regulatory phase is described as a function of the parameters of the model, identifying thereby both theoretically and algorithmically the relevant regulatory variables.     

On the Criticality of Adaptive Boolean Network Robots

Systems poised at a dynamical critical regime, between order and disorder, have been shown capable of exhibiting complex dynamics that balance robustness to external perturbations and rich repertoires of responses to inputs. This property has been exploited in artificial network classifiers, and preliminary results have also been attained in the context of robots controlled by Boolean networks. In this work, we investigate the role of dynamical criticality in robots undergoing online adaptation, i.e., robots that adapt some of their internal parameters to improve a performance metric over time during their activity. We study the behavior of robots controlled by random Boolean networks, which are either adapted in their coupling with robot sensors and actuators or in their structure or both. We observe that robots controlled by critical random Boolean networks have higher average and maximum performance than that of robots controlled by ordered and disordered nets. Notably, in general, adaptation by change of couplings produces robots with slightly higher performance than those adapted by changing their structure. Moreover, we observe that when adapted in their structure, ordered networks tend to move to the critical dynamical regime. These results provide further support to the conjecture that critical regimes favor adaptation and indicate the advantage of calibrating robot control systems at dynamical critical states.