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Boolean Networks as Predictive Models of Emergent Biological Behaviors

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Release : 2024-03-31
Genre : Science
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Book Rating : 962/5 ( reviews)

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Book Synopsis Boolean Networks as Predictive Models of Emergent Biological Behaviors by : Jordan C. Rozum

Download or read book Boolean Networks as Predictive Models of Emergent Biological Behaviors written by Jordan C. Rozum. This book was released on 2024-03-31. Available in PDF, EPUB and Kindle. Book excerpt: This Element shows interacting biological systems at all organizational levels display emergent behavior. Modeling these systems is made challenging by the number and variety of biological components and interactions and the often-incomplete state of system knowledge. Boolean networks have emerged as a powerful tool for modeling these systems. The authors provide a methodological overview of Boolean network models of biological systems. After a brief introduction, they describe the process of building, analyzing, and validating a Boolean model. The authors then present the use of the model to make predictions about the system's response to perturbations and about how to control its behavior. The Element emphasizes the interplay between structural and dynamical properties of Boolean networks and illustrates them in three case studies from disparate levels of biological organization.

Boolean Networks as Predictive Models of Emergent Biological Behaviors

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Release : 2024-03-28
Genre : Science
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Book Rating : 943/5 ( reviews)

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Book Synopsis Boolean Networks as Predictive Models of Emergent Biological Behaviors by : Jordan C. Rozum

Download or read book Boolean Networks as Predictive Models of Emergent Biological Behaviors written by Jordan C. Rozum. This book was released on 2024-03-28. Available in PDF, EPUB and Kindle. Book excerpt: Interacting biological systems at all organizational levels display emergent behavior. Modeling these systems is made challenging by the number and variety of biological components and interactions – from molecules in gene regulatory networks to species in ecological networks – and the often-incomplete state of system knowledge, such as the unknown values of kinetic parameters for biochemical reactions. Boolean networks have emerged as a powerful tool for modeling these systems. This Element provides a methodological overview of Boolean network models of biological systems. After a brief introduction, the authors describe the process of building, analyzing, and validating a Boolean model. They then present the use of the model to make predictions about the system's response to perturbations and about how to control its behavior. The Element emphasizes the interplay between structural and dynamical properties of Boolean networks and illustrates them in three case studies from disparate levels of biological organization.

Attractor Identification and Control in Boolean Models of Plant-pollinator Networks

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Release : 2023
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Book Synopsis Attractor Identification and Control in Boolean Models of Plant-pollinator Networks by : Fatemehsadat Fateminasrollahi

Download or read book Attractor Identification and Control in Boolean Models of Plant-pollinator Networks written by Fatemehsadat Fateminasrollahi. This book was released on 2023. Available in PDF, EPUB and Kindle. Book excerpt: Ecological and biological systems consist of numerous interlinked components that interact and exchange information; such interactions give rise to emergent, collective behaviors that are of interest for ecologists and life scientists. The study of the relationship between the interactions and dynamics of individual components and the emergent dynamics of the system is important because it can lead to the development of control methods to manipulate the collective dynamics. In turn, these control methods can be used for ecological community management or restoration, or for therapeutic medical applications. One promising method to gain a deeper insight into such complex systems is to model the interactions among elements using a network and couple it with a predictive dynamical model. The analysis of such dynamical models provides us with a platform to advance our knowledge of the intricate behaviors exhibited by ecological and biological networks, and it has wide-ranging implications across various domains, spanning conservation efforts, the development of community management strategies, and drug target identification in the context of drug design. The innate challenge that arises when analyzing these models is the large size of the system and the non-linearity of the dynamical processes. Recently, a new approach has been developed by Jorge Gómez Tejeda Zañudo and collaborators that focuses on the stable motifs in the network; stable motifs are minimal positive feedback loops that maintain a specific state regardless of the state of the rest of the components in the system. By characterizing the stable motifs and the conditions that lead to their lock-in, this method can identify the system's dynamic repertoire, predict the outcome of specific interventions and suggest management and control methods. In this dissertation, the main focus is on mutualistic plant-pollinator networks, and specifically on their description by a well-established predictive dynamical model developed by Colin Campbell and collaborators. The study of such systems is of ecological significance as pollinator species face considerable degradation across the world. The loss of pollinator species has a dramatic negative effect on crops as the majority of food crops require pollination to survive. The examination of the reliability and stability of these communities holds great significance for agricultural management and ecological preservation endeavors. There is a great need for measures and methods to predict the magnitude of any cascading effects of species extinction, and for prevention and restoration strategies to maintain the communities. I contribute to this field of study by making it possible for the first time to apply stable motif analysis to plant-pollinator communities. I transform the equations of the existing model by changing threshold functions into suitable logical functions of plant-pollinator networks so that stable motif analysis can be applied to it. I then extend the classical stable motif analysis and introduce a novel method based on stable motifs that determines the stable communities of large plant-pollinator systems efficiently. This method relies on a new concept called the network of functional relationships among stable motifs; I show that these relationships can be leveraged to identify stable communities and accelerate the process significantly. Put into the ecological context, stable motifs can be intuitively interpreted as small groups of species in which species can maintain a specific survival state. I show how such groups of species and the relationships of these groups determine the final community outcomes in plant-pollinator networks. Once the stable communities are characterized, I study their reaction to perturbation and analyze the behavior of the system in the case of species extinction. I extend Boolean modeling concepts, so far only defined for functions of a specific logical form, to the plant-pollinator Boolean threshold functions and introduce a new algorithm to measure the cascading effects caused by species extinction. I then use the information gained from stable motifs to first identify the species whose extinction leads to massive catastrophe in the community and next suggest restoration measures that can be incorporated in ecological sciences. In chapters 1 and 2, I introduce the mutualistic plant-pollinator networks, the Campbell et al. Boolean model of community formation, and the key concepts of Boolean modeling respectively. In chapter 3 I present my contributions to the methodological advancements in the field of Boolean modeling and computational ecology. The methods in this chapter are presented in the context of plant-pollinator networks, but are general and can be implemented in other types of Boolean networks. Chapter 4 describes the properties of the alternative stable states available to the same group of species. Chapter 5 describes the response of plant-pollinator communities to the extinction of a species; specifically, whether there will be cascading effects. This chapter also proposed multiple damage prevention and community restoration measures. The analysis results in these two chapters rely heavily on the concept of stable motifs and the methods introduced in chapter 3. I demonstrate that stable motifs successfully pinpoint the crucial species and this method outperforms the previous well-established measures. Finally, in chapter 6 I study network control in Boolean networks that have a modular structure. In general network control means that by externally fixing the state or the dynamics of a group of nodes, the system as a whole will converge into a desired state or attractor. In this analysis, I aim to identify methods that identify control targets, relying solely on the properties of the network. Taking advantage of the fact that many ecological and biological networks are composed of smaller densely connected modules, I propose a novel module-based method to localize the search for control targets - nodes that if externally controlled, the system will converge into a desired dynamical outcome (e.g., a rich and bio-diverse stable community) or move away from the unwanted dynamical outcome (i.e., full collapse of the community). In this analysis, I study a large ensemble of biologically inspired synthetic Boolean networks to capture the properties of these systems across different levels of modularity. I show that it is considerably more efficient and advantageous to localize the search for control targets in networks with clear modular structure. Chapter 7 presents conclusions and possible future research directions.

Probabilistic Boolean Networks

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Release : 2010-01-21
Genre : Mathematics
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Book Rating : 926/5 ( reviews)

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Book Synopsis Probabilistic Boolean Networks by : Ilya Shmulevich

Download or read book Probabilistic Boolean Networks written by Ilya Shmulevich. This book was released on 2010-01-21. Available in PDF, EPUB and Kindle. Book excerpt: The first comprehensive treatment of probabilistic Boolean networks, unifying different strands of current research and addressing emerging issues.

Predictive Network Modeling And Experimentation In Complex Biological Systems

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Release : 2015
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Book Synopsis Predictive Network Modeling And Experimentation In Complex Biological Systems by : Steven Steinway

Download or read book Predictive Network Modeling And Experimentation In Complex Biological Systems written by Steven Steinway. This book was released on 2015. Available in PDF, EPUB and Kindle. Book excerpt: Biology is incredibly complex -- at the molecular, cellular, tissue, and population level, there exists a tremendous number of discrete interacting components tightly regulating the processes that sustain life. Biological systems have traditionally been viewed in a reductionist manner often literally (and metaphorically) through a magnifying glass, leading to insight into how the individual parts work. Network theory, on the other hand, can be used to put the pieces together, to understand how complex and emergent behaviors arise from the totality of interactions in complex systems, such as those seen in biology. Network theory is the study of systems of discrete interacting components and provides a framework for understanding complex systems. A network-focused investigation of a complex biological system allows for the understanding of the system's emergent properties, for example its function and dynamics. Network dynamics are of particular interest biologically because biological systems are not static but are constantly changing in response to perturbations and environmental stimuli in space and time. Systems level biological analysis has been aided by the recent explosion of high throughput data. This has led to an abundance of quantitative and qualitative information related to the activation of biological systems, but frequently there is still a paucity of kinetic and temporal information. Discrete dynamic modeling provides a means to create predictive models of biological systems by integrating fragmentary and qualitative interaction information. Using discrete dynamic modeling, a structural (static) network of biological regulatory relationships can be translated into a mathematical model without the use of kinetic parameters. This model can describe the dynamics of a biological system (i.e. how it changes over time), both in normal and in perturbation (e.g. disease) scenarios. In this dissertation we present the application of network theory and discrete dynamic modeling integrated with experimental laboratory analysis to understand biological diseases in three contexts. The first is the construction of a network model of epidermal derived growth factor receptor (EGFR) signaling in cancer. We translate this model into two types of discrete models: a Boolean model and a three-state model. We show how the effects of an EGFR inhibitor (such as the drug gefitinib) can suppress tumor growth, and we model how genomic variants can augment the effect of EGFR inhibition in tumor growth. Importantly, we compare discrete modeling outcomes to an alternative modeling framework, which relies on detailed kinetic information, called ordinary differential equation (ODE) modeling and show that both models achieve similar findings. Our results demonstrate that discrete dynamic model can accurately model biomedical systems and make important predictions about the effect a drug will have on a disease (e.g. tumor growth) in the context of various perturbations. Importantly, discrete dynamic models can be employed in the absence of kinetic parameters, making this modeling approach suitable for the many biological systems in which detailed kinetic information is not available. Second, we construct a network model of epithelial-to-mesenchymal transition (EMT), a developmental process hijacked by cancer cells to leave the primary tumor site, invade surrounding tissue, and establish distant metastases. We demonstrate that the EMT network model recapitulates known dysregulations during the induction of EMT and predicts the activation of the Wnt and Sonic hedgehog (SHH) signaling pathways during this process. We confirm the cross-talk between TGF[beta], Wnt and SHH signaling in vitro in multiple human liver cancer cell lines and tumor samples. Next, we use the EMT network model to systematically explore perturbations that suppress EMT, with the ultimate goal of identifying therapeutic interventions that suppress tumor invasion. We computationally explore close to half a million individual and combination perturbations to the EMT network and identify that only a dozen suppress EMT. We test these interventions experimentally and our findings suggest that many predicted interventions suppress the EMT process. Lastly, we construct a model of the enormous ecological community of bacteria that live in our intestines, collectively called the gut microbiome. This model is used to understand the effect of antibiotic treatment and opportunistic C. difficile infection (a devastating and highly prevalent disease entity) on the native microbiome and predict therapeutic probiotic interventions to suppress C. difficile infection. We integrate this modeling with another type of modeling, genome scale metabolic network reconstructions, to understand metabolic differences between community members and to identify the role of metabolism in the observed microbial interactions. In vitro experimental data validate a key result of my computational model, that Barnesiella intestinihominis can in fact suppress C. difficile growth. This novel result suggests that Barnesiella could potentially be used as a probiotic to suppress C. difficile growth.Taken together, the studies presented in this thesis demonstrate the tremendous capacity of network modeling to elucidate biomedical systems. We build networks, construct mathematical models, study network dynamics, and use network-directed insight to guide experiments in critical biomedical areas. The ultimate goal of this work has been to translate network-directed insight into actionable biomedical findings that lead to improved understanding of human disease, enhanced patient care, and a betterment of the human condition.

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