Gene Expression in Microbial Systems for Growth and Metabolism

Gene Expression in Microbial Systems for Growth and Metabolism

Prerak Desai (Utah State University, USA)
Copyright: © 2009 |Pages: 13
DOI: 10.4018/978-1-60566-076-9.ch016
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The use of systems biology to study complex biological questions is gaining ground due to the ever-increasing amount of genetic tools and genome sequences available. As such, systems biology concepts and approaches are increasingly underpinning our concept of microbial physiology. Three tools for use in functional genomics are gene expression, proteomics, and metabolomics. However, these tools produce such large data sets that we sometimes become paralyzed trying to merge the data and link it to form a consistent biological interpretation. Use of functional groupings has relieved some of the issues in merging data for biological meaning. Statistical analysis and visualization of these multi-dimension data sets are needed to aid the microbiologist, which brings additional methods that are often not familiar. Progress is being made to bring these diverse data types together to understand fundamental metabolic processes and pathways. These efforts are paying tremendous dividends in our understanding of how microbes live, grow, survive, and metabolize nutrients. These insights allow metabolic engineering to progress and allow scientists to further define the mechanisms of metabolism.
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Systems biology brought a great challenge to the microbial world – produce genome-scale data that is integrated into a complete biological picture using specific genes. In spite of this challenge, systems biology is increasingly underpinning our concept of microbial physiology based on genome sequence. Initially, production of a genome sequence limited implementation of this paradigm. However, the rate at which new genome content is accumulating is staggering and is the basis of new avenues for discovery.

Publicly available genome sequence now exceeds 700 finished genomes with an additional 1,700 genomes in process of sequencing that provides access to at least 3,600 individual microbial genomes with an additional 116 metagenome projects underway (GOLD, 2008; These projects are challenging scientists’ ability to collect, process, and overlay a biologically meaningful interpretation of the data. Application of that information to make biologically informed decisions is also a daunting challenge that requires a fresh perspective and new skill sets that leverage genomic-based tools to answer specific biological questions.

The heart of the systems biology discovery lies in the new fields of comparative and functional genomics, along with proteomic and metabolite profiles (Fields, 2000). Comparison of genomes to assess the link between structural similarity and functional expression is fully enabled with access to genome content. Comparative analyses of bacterial genomes provide new information about the dynamic interchange of DNA between microbes (Hughes, 2000). Comparing sequenced genomes is an excellent approach to explore genome plasticity and how it impacts the metabolism of microbes.

Approaching microbial metabolism from a systems biology perspective is a new position that requires scientists to think of systems of activities that is composed of multiple individuals to carry out those activities. Use of gene ontologies and (GO) and clusters of orthologous groups (COG’s) are very helpful for this aspect of comparison since specific and common terms are used in a hierarchical classification system, and are essential when using functional genomic tools to drill down to individual conversations (i.e. activities). These tools include gene expression profiling, protein expression profiling, metabolomics profiles, and new statistical methods.

Functional genomics must incorporate data from each set of tools to examine how organisms utilize the genome potential (via gene expression initially). Since most genomes have thousands of genes that are monitored the task is like trying to monitor all the individual conversations in a crowded stadium at one moment in time. In essence, functional genomics documents a cell’s many “conversations” as they occur simultaneously. The conversations are defined by genes expression (gene arrays), protein interactions (proteomics), and small molecule biochemistry (metabolomics) that create a multi-dimensional view of the cell. Deciphering these conversations in turn outlines the web of actors in the metabolic networks, providing an unprecedented view of how a living cell carries out the many functions of growth, survival, pathogenicity, and metabolism.

Production of multi-dimensional data using these techniques produce very different types of data that need a common thread that links the data types. Such large data sets lead to an interpretational paralysis that limits the linkage between the functional genomics data and biological relevance or meaning. Therefore, the analytical phase must seek to fully integrate all of these tools using new statistical tools that are also unfamiliar to most microbiologists, which often exacerbates interpretation difficulties when the genotype and the phenotype are at odds. Taken together, it is clear that the use of bioinformatics is essential for mining genome content, but also essential to provide bring new scientific abilities that truly bring biologically meaningful insights via systems biology.

Key Terms in this Chapter

Bioconductor: ( ): An open source and open development software project for the analysis and comprehension of genomic data.

Significance Analysis Of Microarrays: (SAM; An Excel plug-in that is used to analyze microarray data.

R: ( ): R is a language and environment for statistical computing and graphics. R provides a wide variety of statistical (linear and nonlinear modeling, classical statistical tests, time-series analysis, classification, clustering, etc.) and graphical techniques that is highly extensible.

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Editorial Advisory Board
Table of Contents
Ralf Herwig
Andriani Daskalaki
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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