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      Boolean network simulations for life scientists

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          Abstract

          Modern life sciences research increasingly relies on computational solutions, from large scale data analyses to theoretical modeling. Within the theoretical models Boolean networks occupy an increasing role as they are eminently suited at mapping biological observations and hypotheses into a mathematical formalism. The conceptual underpinnings of Boolean modeling are very accessible even without a background in quantitative sciences, yet it allows life scientists to describe and explore a wide range of surprisingly complex phenomena. In this paper we provide a clear overview of the concepts used in Boolean simulations, present a software library that can perform these simulations based on simple text inputs and give three case studies. The large scale simulations in these case studies demonstrate the Boolean paradigms and their applicability as well as the advanced features and complex use cases that our software package allows. Our software is distributed via a liberal Open Source license and is freely accessible from http://booleannet.googlecode.com

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          Most cited references30

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          Modeling and simulation of genetic regulatory systems: a literature review.

          In order to understand the functioning of organisms on the molecular level, we need to know which genes are expressed, when and where in the organism, and to which extent. The regulation of gene expression is achieved through genetic regulatory systems structured by networks of interactions between DNA, RNA, proteins, and small molecules. As most genetic regulatory networks of interest involve many components connected through interlocking positive and negative feedback loops, an intuitive understanding of their dynamics is hard to obtain. As a consequence, formal methods and computer tools for the modeling and simulation of genetic regulatory networks will be indispensable. This paper reviews formalisms that have been employed in mathematical biology and bioinformatics to describe genetic regulatory systems, in particular directed graphs, Bayesian networks, Boolean networks and their generalizations, ordinary and partial differential equations, qualitative differential equations, stochastic equations, and rule-based formalisms. In addition, the paper discusses how these formalisms have been used in the simulation of the behavior of actual regulatory systems.
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            Probabilistic Boolean Networks: a rule-based uncertainty model for gene regulatory networks.

            Our goal is to construct a model for genetic regulatory networks such that the model class: (i) incorporates rule-based dependencies between genes; (ii) allows the systematic study of global network dynamics; (iii) is able to cope with uncertainty, both in the data and the model selection; and (iv) permits the quantification of the relative influence and sensitivity of genes in their interactions with other genes. We introduce Probabilistic Boolean Networks (PBN) that share the appealing rule-based properties of Boolean networks, but are robust in the face of uncertainty. We show how the dynamics of these networks can be studied in the probabilistic context of Markov chains, with standard Boolean networks being special cases. Then, we discuss the relationship between PBNs and Bayesian networks--a family of graphical models that explicitly represent probabilistic relationships between variables. We show how probabilistic dependencies between a gene and its parent genes, constituting the basic building blocks of Bayesian networks, can be obtained from PBNs. Finally, we present methods for quantifying the influence of genes on other genes, within the context of PBNs. Examples illustrating the above concepts are presented throughout the paper.
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              Boolean formalization of genetic control circuits.

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                Author and article information

                Journal
                Source Code Biol Med
                Source Code for Biology and Medicine
                BioMed Central
                1751-0473
                2008
                14 November 2008
                : 3
                : 16
                Affiliations
                [1 ]Huck Institutes for the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA
                [2 ]Physics Department, Pennsylvania State University, University Park, Pennsylvania, USA
                [3 ]Biology Department, Pennsylvania State University, University Park, Pennsylvania, USA
                [4 ]College of Medicine, Hershey, Pennsylvania, USA
                Article
                1751-0473-3-16
                10.1186/1751-0473-3-16
                2603008
                19014577
                0a4b02a9-7e9b-4747-b7d7-eb6a4fa9a60d
                Copyright © 2008 Albert et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 September 2008
                : 14 November 2008
                Categories
                Methodology

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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