Dynamical complexity of discrete time regulatory networks

Genetic regulatory networks are usually modeled by systems of coupled differential equations and by finite state models, better known as logical networks, are also used. In this paper we consider a class of models of regulatory networks which present both discrete and continuous aspects. Our models consist of a network of units, whose states are quantified by a continuous real variable. The state of each unit in the network evolves according to a contractive transformation chosen from a finite collection of possible transformations, according to a rule which depends on the state of the neighboring units. As a first approximation to the complete description of the dynamics of this networks we focus on a global characteristic, the dynamical complexity, related to the proliferation of distinguishable temporal behaviors. In this work we give explicit conditions under which explicit relations between the topological structure of the regulatory network, and the growth rate of the dynamical complexity can be established. We illustrate our results by means of some biologically motivated examples.Comment: 28 pages, 4 figure

An investigation of genetic algorithm-based feature selection techniques applied to keystroke dynamics biometrics

Due to the continuous use of social networks, users can be vulnerable to online situations such as paedophilia treats. One of the ways to do the investigation of an alleged pedophile is to verify the legitimacy of the genre that it claims. One possible technique to adopt is keystroke dynamics analysis. However, this technique can extract many attributes, causing a negative impact on the accuracy of the classifier due to the presence of redundant and irrelevant attributes. Thus, this work using the wrapper approach in features selection using genetic algorithms and as KNN, SVM and Naive Bayes classifiers. Bringing as best result the SVM classifier with 90% accuracy, identifying what is most suitable for both bases

Understanding the Regulation of Predatory and Anti-Prey Behaviours for an Artificial Organism

An organism’s behaviour can be categorised as being either predatory or anti-prey. Predatory behaviours are behaviours that try to improve the life of an organism. Anti-prey behaviours are those that attempt to prevent death. Regulation between these two opposing behaviours is necessary to ensure survivability—and gene regulatory networks and metabolic networks are the mechanisms that provide this regulation. We know that such regulatory behaviour is encoded in an organism’s genes. The question is, how is it encoded? The understanding of this encoding can help with the development of an artificial organism, for example an autonomous robotic system; whereby the robot will have the ability to autonomously regulate the switching between the opposing behaviours using this encoded mechanism, in order to ensure its sustainable and continuous system operations. This paper aims to look into the properties of an artificial bio-chemical network consisting of a genetic regulatory network and a metabolic network that can provide these capabilities

Unifying metabolic networks, regulatory constraints, and resource allocation

Metabolic and gene regulatory networks are two classic models of systems biology. Biologically, gene regulatory networks are the control system of protein expression while metabolic networks, especially the genome-scale reconstructions consist of thousands of enzymatic reactions breaking down nutrients into precursors and energy to support the cellular survival. Metabolic-genetic networks, in addition, include the translational processes as an integrated model of classical metabolic networks and the gene expression machinery. Conversely, genetic regulation is also affected by the metabolic activities that provide feedbacks and precursors to the regulatory system. Thus, the two systems are highly interactive and depend on each other. Up to now, various efforts have been made to bridge the two network types. Yet, the dynamic integration of metabolic networks and genetic regulation remains a major challenge in computational systems biology. This PhD thesis is a contribution to mathematical modeling approaches for studying metabolic-regulatory systems. Inspired by regulatory flux balance analysis (rFBA), we first propose an analytic pipeline to explore the optimal solution space in rFBA. Then, our efforts focus on the dynamic combination of metabolic networks together with enzyme production costs and genetic regulation. For this purpose, we first explore the intuitive idea that incorporates Boolean regulatory rules while iterating resource balance analysis. However, with the iterative strategy, the gene expression states are only updated in discrete time steps. Furthermore, formalizing the metabolic-regulatory networks (MRNs) by hybrid automata provides a new mathematical framework that allows the quantitative integration of the metabolic-genetic network with the genetic regulation in a hybrid discrete-continuous system. For the application of this theoretical formalization, we develop a constraint-based approach regulatory dynamic enzyme-cost flux balance analysis (r-deFBA) as an optimal control strategy for the hybrid automata representing MRNs. This allows the prediction of optimal regulatory state transitions, dynamics of metabolism, and resource allocation capable of achieving a maximal biomass production over a time interval. Finally, this PhD project ends with a chapter on perspectives; we apply the theory of product automata to model the dynamics at population-level, integrating continuous metabolism and discrete regulatory states

Delay-dependent Stability of Genetic Regulatory Networks

Genetic regulatory networks are biochemical reaction systems, consisting of a network of interacting genes and associated proteins. The dynamics of genetic regulatory networks contain many complex facets that require careful consideration during the modeling process. The classical modeling approach involves studying systems of ordinary differential equations (ODEs) that model biochemical reactions in a deterministic, continuous, and instantaneous fashion. In reality, the dynamics of these systems are stochastic, discrete, and widely delayed. The first two complications are often successfully addressed by modeling regulatory networks using the Gillespie stochastic simulation algorithm (SSA), while the delayed behavior of biochemical events such as transcription and translation are often ignored due to their mathematically difficult nature. We develop techniques based on delay-differential equations (DDEs) and the delayed Gillespie SSA to study the effects of delays, in both continuous deterministic and discrete stochastic settings. Our analysis applies techniques from Floquet theory and advanced numerical analysis within the context of delay-differential equations, and we are able to derive stability sensitivities for biochemical switches and oscillators across the constituent pathways, showing which pathways in the regulatory networks improve or worsen the stability of the system attractors. These delay sensitivities can be far from trivial, and we offer a computational framework validated across multiple levels of modeling fidelity. This work suggests that delays may play an important and previously overlooked role in providing robust dynamical behavior for certain genetic regulatory networks, and perhaps more importantly, may offer an accessible tuning parameter for robust bioengineering