Discrete Networks as a Suitable Approach for the Analysis of Genetic Regulation

Discrete Networks as a Suitable Approach for the Analysis of Genetic Regulation

Elizabeth Santiago-Cortés (Universidad Nacional Autónoma de México, Mexico)
Copyright: © 2009 |Pages: 11
DOI: 10.4018/978-1-60566-076-9.ch031
OnDemand PDF Download:
$37.50

Abstract

Biological systems are composed of multiple interacting elements; in particular, genetic regulatory networks are formed by genes and their interactions mediated by transcription factors. The establishment of such networks is critical to guarantee the reliability of transcriptional performance in any organism. The study of genetic regulatory networks as dynamical systems is a helpful methodology to understand the transcriptional behavior of the genome. From a number of theoretical studies, it is known that networks present a complex dynamical behavior that includes stability, redundancy, homeostasis, and multistationarity. In this chapter we present some particular biological processes modeled as discrete networks to show that the theoretical properties of networks have a clear biological interpretation.
Chapter Preview
Top

Introduction

Development of multicellular organisms requires the coordinated accomplishment of many molecular and cellular processes, like division and differentiation. Regulation of those processes must be very reliable, capable of resisting fluctuations of the internal and external environments. Without such homeostatic capacity, the viability of the organism would be compromised. For instance, unrestrained division of some cells may lead to the appearance of tumors, which may possibly cause death. Cellular processes are finely controlled by a number of regulatory molecules, among them transcription factors. These are present inside cells at low quantities, and variations in their concentrations might alter cellular fate.

Modern high-throughput techniques have greatly increased the rate at which genomes are sequenced and genes are identified. Nonetheless, classic biochemical and physiological studies are necessary to identify the functions and molecular targets of the coded proteins. Of interest for this chapter are those genes that code for transcription factors. These proteins bind to cis-regulatory sequences of other genes, controlling or somehow modifying the transcriptional rate of their targets. If these targets code for other transcription factors, then and interdependence is created among genes forming a genetic regulatory network (Kauffman, 1991). The existence of regulatory networks have as a result the controlled and coordinated expression of a large group of genes. While these ideas are commonly accepted, biologists are not usually aware of the global properties of these networks. The reason is that they have some properties that are not evident or intuitive.

Modeling regulatory networks is very useful to understand how different gene expression patterns arise and are maintained. All cells in an organism have the same genes, and therefore the same global genetic regulatory network. Yet, each cell type differs from others in their particular molecular profile, i.e. in their patterns of transcriptionally active genes and the presence of other molecular markers. In addition, such genetic activation patterns are stable, in a normal situation cells do not differentiate continually from one type into another. This characteristics are due to the global properties of the underlying genetic regulatory networks (Kauffman, 1993; Thomas et al., 1995).

It is a common practice to graphically represent transcriptional regulatory interactions using graphs, since they are intuitive and easy to understand. However, the knowledge of the connectivity is not enough to determine the behavior of a regulatory network. For example, it is not possible to know how many steady states of genetic activation are allowed by a particular network, neither if those steady states are stable or not. To know these properties, it is necessary to incorporate the transcriptional rate of each gene as a function of its regulators. By doing this, a genetic regulatory network is translated into a dynamical system.

There is a large number of methodologies to analyze regulatory networks as dynamical systems (de Jong, 2002). Most modelers prefer to represent the dynamical system in the form of a set of ordinary differential equations that describe the transcriptional rate of genes. However, for most biological systems there is a lack of quantitative experimental information to fit the whole set of parameters in the system of equations. In contrast, there is a wealth of published experimental results that include qualitative information regarding the spatio-temporal activation of genes. Hence, some modelers have opted to model genetic regulatory networks as discrete dynamical systems.

It might appear at first sight that modeling using discrete variables is somehow inferior to the use of continuous variables, but it has been shown that continuous and discrete models share many qualitative dynamic features (Bagley and Glass, 1996; Glass, 1975; Glass and Kauffman, 1973; Muraille et al., 1996; Mendoza and Xenarios, 2006). In this chapter we present some properties of discrete networks, as well as some biological examples of regulatory genetic networks modeled as discrete state dynamical systems. These topics will show the reader that many important aspects of regulatory networks can be appropriately studied with the use of discrete dynamical systems.

Key Terms in this Chapter

Attractor: A set of states of a dynamical system towards which the system approaches asymptotically. Region of the state space towards which all the trajectories of a set of initial states converge.

Steady State: In a dynamical system, a state where none of the variables in the system changes with time.

Multistationarity: The property of a dynamical system of having two or more steady states.

Graph: A collection of points and lines connecting a subset of them. The points of a graph are commonly known as vertices or nodes. Similarly, lines connecting the vertices of a graph are known as edges, arcs, or interactions.

Feedback Loop: A circular chain of interactions, such that each element in the loop influences its own future level of activation. Feedback loops are also known as circuits.

Dynamical System: A set of equations that describe the change of some variables over time.

Complete Chapter List

Search this Book:
Reset
Editorial Advisory Board
Table of Contents
Foreword
Ralf Herwig
Preface
Andriani Daskalaki
Acknowledgment
Andriani Daskalaki
Chapter 1
Peter Ghazal
An increasing number of biological experiments and more recently clinical based studies are being conducted using large-scale genomic, proteomic and... Sample PDF
Pathway Biology Approach to Medicine
$37.50
Chapter 2
Peter Wellstead, Sree Sreenath, Kwang-Hyun Cho
In this chapter the authors describe systems and control theory concepts for systems biology and the corresponding implications for medicine. The... Sample PDF
Systems and Control Theory for Medical Systems Biology
$37.50
Chapter 3
S. Nikolov
In this chapter we investigate how the inclusion of time delay alters the dynamic properties of (a) delayed protein cross talk model, (b) time delay... Sample PDF
Mathematical Description of Time Delays in Pathways Cross Talk
$37.50
Chapter 4
Elisabeth Maschke-Dutz
In this chapter basic mathematical methods for the deterministic kinetic modeling of biochemical systems are described. Mathematical analysis... Sample PDF
Deterministic Modeling in Medicine
$37.50
Chapter 5
Andrew Kuznetsov
Biologists have used a reductionist approach to investigate the essence of life. In the last years, scientific disciplines have merged with the aim... Sample PDF
Synthetic Biology as a Proof of Systems Biology
$37.50
Chapter 6
Tuan D. Pham
Computational models have been playing a significant role for the computer-based analysis of biological and biomedical data. Given the recent... Sample PDF
Computational Models for the Analysis of Modern Biological Data
$37.50
Chapter 7
Vanathi Gopalakrishnan
This chapter provides a perspective on 3 important collaborative areas in systems biology research. These areas represent biological problems of... Sample PDF
Computer Aided Knowledge Discovery in Biomedicine
$37.50
Chapter 8
Thomas Meinel
The function of proteins is a main subject of research in systems biology. Inference of function is now, more than ever, required by the upcoming of... Sample PDF
Function and Homology of Proteins Similar in Sequence: Phylogenetic Profiling
$37.50
Chapter 9
Nikolaos G. Sgourakis, Pantelis G. Bagos, Stavros J. Hamodrakas
GPCRs comprise a wide and diverse class of eukaryotic transmembrane proteins with well-established pharmacological significance. As a consequence of... Sample PDF
Computational Methods for the Prediction of GPCRs Coupling Selectivity
$37.50
Chapter 10
Pantelis G. Bagos, Stavros J. Hamodrakas
ß-barrel outer membrane proteins constitute the second and less well-studied class of transmembrane proteins. They are present exclusively in the... Sample PDF
Bacterial ß-Barrel Outer Membrane Proteins: A Common Structural Theme Implicated in a Wide Variety of Functional Roles
$37.50
Chapter 11
L.K. Flack
Clustering methods are used to place items in natural patterns or convenient groups. They can be used to place genes into clusters to have similar... Sample PDF
Clustering Methods for Gene-Expression Data
$37.50
Chapter 12
George Sakellaropoulos, Antonis Daskalakis, George Nikiforidis, Christos Argyropoulos
The presentation and interpretation of microarray-based genome-wide gene expression profiles as complex biological entities are considered to be... Sample PDF
Uncovering Fine Structure in Gene Expression Profile by Maximum Entropy Modeling of cDNA Microarray Images and Kernel Density Methods
$37.50
Chapter 13
Wasco Wruck
This chapter describes the application of the BeadArrayTM technology for gene expression profiling. It introduces the BeadArrayTM technology, shows... Sample PDF
Gene Expression Profiling with the BeadArrayTM Platform
$37.50
Chapter 14
Djork-Arné Clevert, Axel Rasche
Readers shall find a quick introduction with recommendations into the preprocessing of Affymetrix GeneChip® microarrays. In the rapidly growing... Sample PDF
The Affymetrix GeneChip® Microarray Platform
$37.50
Chapter 15
Jacek Majewski
Eukaryotic genes have the ability to produce several distinct products from a single genomic locus. Recent developments in microarray technology... Sample PDF
Alternative Isoform Detection Using Exon Arrays
$37.50
Chapter 16
Prerak Desai
The use of systems biology to study complex biological questions is gaining ground due to the ever-increasing amount of genetic tools and genome... Sample PDF
Gene Expression in Microbial Systems for Growth and Metabolism
$37.50
Chapter 17
Heike Stier
Alternative splicing is an important part of the regular process of gene expression. It controls time and tissue dependent expression of specific... Sample PDF
Alternative Splicing and Disease
$37.50
Chapter 18
Axel Kowald
Aging is a complex biological phenomenon that practically affects all multicellular eukaryotes. It is manifested by an ever increasing mortality... Sample PDF
Mathematical Modeling of the Aging Process
$37.50
Chapter 19
Evgenia Makrantonaki
This chapter introduces an in vitro model as a means of studying human hormonal aging. For this purpose, human sebaceous gland cells were maintained... Sample PDF
The Sebaceous Gland: A Model of Hormonal Aging
$37.50
Chapter 20
R. Seigneuric, N.A.W. van Riel, M.H.W. Starmans, A. van Erk
Complex diseases such as cancer have multiple origins and are therefore difficult to understand and cure. Highly parallel technologies such as DNA... Sample PDF
Systems Biology Applied to Cancer Research
$37.50
Chapter 21
Matej Orešic, Antonio Vidal-Puig
In this chapter the authors report on their experience with the analysis and modeling of data obtained from studies of animal models related to... Sample PDF
Systems Biology Strategies in Studies of Energy Homeostasis In Vivo
$37.50
Chapter 22
Axel Rasche
We acquired new computational and experimental prospects to seek insight and cure for millions of afflicted persons with an ancient malady. Type 2... Sample PDF
Approaching Type 2 Diabetes Mellitus by Systems Biology
$37.50
Chapter 23
Alia Benkahla, Lamia Guizani-Tabbane, Ines Abdeljaoued-Tej, Slimane Ben Miled, Koussay Dellagi
This chapter reports a variety of molecular biology informatics and mathematical methods that model the cell response to pathogens. The authors... Sample PDF
Systems Biology and Infectious Diseases
$37.50
Chapter 24
Daniela Albrecht, Reinhard Guthke
This chapter describes a holistic approach to understand the molecular biology and infection process of human-pathogenic fungi. It comprises the... Sample PDF
Systems Biology of Human-Pathogenic Fungi
$37.50
Chapter 25
Jessica Ahmed
Secretases are aspartic proteases, which specifically trim important, medically relevant targets such as the amyloid-precursor protein (APP) or the... Sample PDF
Development of Specific Gamma Secretase Inhibitors
$37.50
Chapter 26
Paul Wrede
Peptides fulfill many tasks in controlling and regulating cellular functions and are key molecules in systems biology. There is a great demand in... Sample PDF
In Machina Systems for the Rational De Novo Peptide Design
$37.50
Chapter 27
Ferda Mavituna, Raul Munoz-Hernandez, Ana Katerine de Carvalho Lima Lobato
This chapter summarizes the fundamentals of metabolic flux balancing as a computational tool of metabolic engineering and systems biology. It also... Sample PDF
Applications of Metabolic Flux Balancing in Medicine
$37.50
Chapter 28
Roberta Alfieri, Luciano Milanesi
This chapter aims to describe data integration and data mining techniques in the context of systems biology studies. It argues that the different... Sample PDF
Multi-Level Data Integration and Data Mining in Systems Biology
$37.50
Chapter 29
Hendrik Hache
In this chapter, different methods and applications for reverse engineering of gene regulatory networks that have been developed in recent years are... Sample PDF
Methods for Reverse Engineering of Gene Regulatory Networks
$37.50
Chapter 30
Alok Mishra
This chapter introduces the techniques that have been used to identify the genetic regulatory modules by integrating data from various sources. Data... Sample PDF
Data Integration for Regulatory Gene Module Discovery
$37.50
Chapter 31
Elizabeth Santiago-Cortés
Biological systems are composed of multiple interacting elements; in particular, genetic regulatory networks are formed by genes and their... Sample PDF
Discrete Networks as a Suitable Approach for the Analysis of Genetic Regulation
$37.50
Chapter 32
A. Maffezzoli
In this chapter, authors review main methods, approaches, and models for the analysis of neuronal network data. In particular, the analysis concerns... Sample PDF
Investigating the Collective Behavior of Neural Networks: A Review of Signal Processing Approaches
$37.50
Chapter 33
Paolo Vicini
This chapter describes the System for Population Kinetics (SPK), a novel Web service for performing population kinetic analysis. Population kinetic... Sample PDF
The System for Population Kinetics: Open Source Software for Population Analysis
$37.50
Chapter 34
Julia Adolphs
This chapter introduces the theory of optical spectra and excitation energy transfer of light harvesting complexes in photosynthesis. The light... Sample PDF
Photosynthesis: How Proteins Control Excitation Energy Transfer
$37.50
Chapter 35
Michael R. Hamblin
Photodynamic therapy (PDT) is a rapidly advancing treatment for multiple diseases. PDT involves the administration of a nontoxic drug or dye known... Sample PDF
Photodynamic Therapy: A Systems Biology Approach
$37.50
Chapter 36
Andriani Daskalaki
Photodynamic Therapy (PDT) involves administration of a photosensitizer (PS) either systemically or locally, followed by illumination of the lesion... Sample PDF
Modeling of Porphyrin Metabolism with PyBioS
$37.50
Chapter 37
Alexey R. Brazhe, Nadezda A. Brazhe, Alexey N. Pavlov, Georgy V. Maksimov
This chapter describes the application of interference microscopy and double-wavelet analysis to noninvasive study of cell structure and function.... Sample PDF
Interference Microscopy for Cellular Studies
$37.50
Chapter 38
Cathrin Dressler, Olaf Minet, Urszula Zabarylo, Jürgen Beuthan
This chapter deals with the mitochondrias’ stress response to heat, which is the central agent of thermotherapy. Thermotherapies function by... Sample PDF
Fluorescence Imaging of Mitochondrial Long-Term Depolarization in Cancer Cells Exposed to Heat-Stress
$37.50
Chapter 39
Athina Theodosiou, Charalampos Moschopoulos, Marc Baumann, Sophia Kossida
In previous years, scientists have begun understanding the significance of proteins and protein interactions. The direct connection of those with... Sample PDF
Protein Interactions and Diseases
$37.50
Chapter 40
Bernard de Bono
From a genetic perspective, disease can be interpreted in terms of a variation in molecular sequence or expression (dose) that impairs normal... Sample PDF
The Breadth and Depth of BioMedical Molecular Networks: The Reactome Perspective
$37.50
Chapter 41
Jorge Numata
Thermodynamics is one of the best established notions in science. Some recent work in biomolecular modeling has sacrificed its rigor in favor of... Sample PDF
Entropy and Thermodynamics in Biomolecular Simulation
$37.50
Chapter 42
Isabel Reinecke, Peter Deuflhard
In this chapter some model development concepts can be used for the mathematical modeling in physiology as well as a graph theoretical approach for... Sample PDF
Model Development and Decomposition in Physiology
$37.50
Chapter 43
Mohamed Derouich
Throughout the world, seasonal outbreaks of influenza affect millions of people, killing about 500,000 individuals every year. Human influenza... Sample PDF
A Pandemic Avian Influenza Mathematical Model
$37.50
Chapter 44
Mohamed Derouich
Dengue fever is a re-emergent disease affecting more than 100 countries. Its incidence rate has increased fourfold since 1970 with nearly half the... Sample PDF
Dengue Fever: A Mathematical Model with Immunization Program
$37.50
Chapter 45
Ross Foley
The field of histopathology has encountered a key transition point with the progressive move towards use of digital slides and automated image... Sample PDF
Automated Image Analysis Approaches in Histopathology
$37.50
About the Contributors