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Systems biology is a relatively new biological study field that focuses on the systematic study of complex interactions in biological systems, thus using a new perspective (integration instead of reduction) to study them. Particularly from year 2000 onwards, the term is used widely in the biosciences, and in a variety of contexts. Systems biology is the study of the interconnected aspect of molecular, cellular, tissue, whole animal and ecological processes, and comprises mathematical and mechanistic studies of dynamical, mesoscopic, open, spatiotemporally defined, nonlinear, complex systems that are far from thermodynamic equilibrium.
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Table of Contents
Related Titles
Title Page
Copyright
Preface and Commentary
List of Contributors
Part I: Biological Basis of Systems Biology
1 Systems Biology
1 Introduction
2 What Is Systems Understanding?
3 Why Are Biological Systems Different?
4 Systems Biology Modeling
5 Future Prospects of Systems Biology
References
2 Developmental Cell Biology
1 Historical Perspective
2 Cell Activities Underlying Development
3 Cell Differentiation
4 The Cell Cycle and Development
5 Organogenesis
6 Stem Cells
7 Chimeras
8 microRNAs (miRNAs)
9 In vitro Fertilization
References
3 Principles and Applications of Embryogenomics
1 Introduction
2 Approaches
3 Model Organisms for Embryogenomics
4 Conclusions
References
4 Interactome
1 Introduction
2 Experimental Techniques for Detecting Protein Interactions
3 Computational Prediction of Protein Interactions
4 Exploring the Topology of the Interactome
5 Comparing Protein–Protein Interaction Networks
6 Databases of Protein and Domain Interactions
7 Applications
8 Looking Ahead: Towards the Dynamic Interactome
Acknowledgments
References
5 Protein Abundance Variation
1 Introduction
2 Biochemical Aspects Affecting Protein Abundance in Prokaryotes
3 Extracellular Causes Influencing Protein Abundance in Prokaryotes
4 Biochemical Aspects Affecting Protein Abundance in Eukaryotes
5 Other Factors Influencing Protein Abundance in Eukaryotes
6 Techniques Used to Measure Protein Abundance
7 Concluding Remarks and Outlook
Acknowledgments
References
Part II: Systems Biology of Evolution
6 Genetic Variation and Molecular Darwinism
1 Introduction
2 Principles of Molecular Evolution
3 Genetic Variation in Bacteria
4 Local Changes in the DNA Sequences
5 Intragenomic DNA Rearrangements
6 DNA Acquisition
7 The Three Natural Strategies Generating Genetic Variations Contribute Differently to the Evolutionary Process
8 Evolution Genes and Their Own Second-Order Selection
9 Arguments for a General Relevance of the Theory of Molecular Evolution for All Living Organisms
10 Systemic Aspects of Biological and Terrestrial Evolution
11 Conceptual Aspects of the Theory of Molecular Evolution
References
7 Systematics and Evolution
1 The Beginning of Molecular Systematics
2 The Molecular Assumption
3 DNA Hybridization
4 Mitochondrial DNA
5 DNA Sequences
6 Repeated (Retro)Transposons
7 “Evo-Devo”
8 Positional Information and Shape
9 “Mutation”
10 Toward a Theory of Evolutionary Change
11 Molecules and Systematics: Looking Toward the Future
References
8 Evolution of the Protein Repertoire
1 The First Proteins
2 Organization of the Modern Protein Repertoire
3 Protein Sequence and Its Evolution
4 Protein Structure and Its Evolution
5 Protein Function and Its Evolution
6 Protein Evolution in Human Hands
7 Lessons from the Evolution of the Protein Repertoire
References
Part III: Modeling of Biological Systems
9 Chaos in Biochemistry and Physiology
1 Introduction
2 Systems Biology and the Complex Systems Approach: Chaos in Context
3 Reconstructing the Underlying Dynamics of Complex Systems
4 Chaos, Randomness, and (Colored) Noise
5 Nonlinear Time Series Analysis: Conceptual Theoretical and Analytic Tools for Chaos Detection and Characterization
6 Periodic and Non-Periodic Dynamics
7 Biochemical and Physiological Chaos
8 Chaos in Dynamics of Heart and Brain?
9 Concluding Remarks: The Status and a Prospective for Chaos
10 Acknowledgments
References
10 Computational Biology
1 Introduction
2 Sequencing Genomes
3 Molecular Sequence Analysis
4 Molecular Structure Prediction
5 Analysis of Molecular Interactions
6 Molecular Networks
7 Analysis of Expression Data
8 Protein Function Prediction
9 Computational Biology of Diseases
10 Perspectives
Acknowledgments
Note on the Second Edition on This Chapter
References
11 Dynamics of Biomolecular Networks
1 Introduction
2 Boolean Dynamics Models
3 Continuous Dynamics Models
References
12 AR E-Cell
1 Introduction
2 Biological Modeling and Simulation Tools
3 The E-Cell System
4 Practical Applications
5 Concluding Remarks
References
13 Fractals in Biology and Medicine
1 Introduction
2 The Irruption of Fractal Geometry in Biology and Medicine
3 Fractal Criteria
4 Fractalomics
5 Concluding Remarks
Acknowledgments
References
14 Models of Cell Migration
1 Overview
2 Phenomenology and Mechanisms of Cell Motility
3 Mechanics of Migration
4 Chemotaxis
5 Multi-Photon Imaging of Lymphocyte Migration
6 Mathematical Models of Cell Migration
7 Mathematical Models of Tissue Organization
8 Conclusions
References
15 Protein Modeling
1 Introduction
2 Structure Prediction Methods
3 Structure-Based Modeling
4 Simulations of Protein Dynamics
5 Example Applications
6 Perspectives
Acknowledgments
References
16 System Models for Inference on Mechanisms of Neuronal Dynamics
1 General System Theory and Systems Biology
2 A General Form for System Models
3 System Models for Inferring Functional Integration and Effective Connectivity from Neuroimaging Data
4 Regression-Based Models of Effective Connectivity
5 Vector Autoregressive Models and Granger Causality
6 The Importance of Biophysical Forward Models
7 Dynamic Causal Modeling (DCM) for fMRI
8 Bayesian Model Selection (BMS)
9 Nonlinear, Two-State and Stochastic DCMs for fMRI
10 DCM for Electrophysiological Data
11 Future Applications and Challenges for Inferring Effective Connectivity from Neuroimaging and Electrophysiological Data
References
17 Systems Biology of the Liver
1 Background
2 Liver Physiology, Biochemistry, and Disease
3 Modeling of Genetic and Metabolic Phenomena in the Liver
4 Modeling Liver Physiology
5 A Composite Systems Biology Model to Predict Glucose Homeostasis
6 Conclusions and Future Developments
References
Part IV: Systems Biology in Medicine and Disease
18 Inferring Networks for Diseases
1 Common Diseases Are Complex
2 Network-Based Analysis: A Brief Summary
3 Networks in Diseases
4 Disease-Scale Network-Based Analyses of a Model Disease: Seasonal Allergic Rhinitis
5 Graph Theoretical Tools for Network-Based Analysis
6 An Example of a Combinatorial, Network-Based Study to Identify a Disease Module in SAR
7 Problems in Applying Network-Based Analyses to Clinical Research
8 Future Perspectives
9 Conclusions
References
19 Personalized Medicine (Predictive and Preventive)
1 Some History and Some Fundamentals
2 Where Are We Today?
3 Summing Up
4 Examples of Recent Advances in Personalized Medicine Based on Pharmacogenomic Findings
5 Analysis of Variability in Drug Response: Sources, Surprises, and Solutions
6 How Variance Aggregates in a Multicomponent System
7 Some Provisos
8 An Overview
References
Part V: Systems Biology of Organisms
20 Microbiomes
1 Introduction
2 History of Microbial Diversity Studies
3 Microbiomes
4 Single-Cell Genomics
5 Sequence Technologies and Tools
6 Future Perspectives
Acknowledgments
References
21 AR Synthetic Biology
1 Introduction
2 DNA Assembly and Modification
3 Modular Parts and Circuits
4 Spatial Regulation
5 The Synthetic Cell
6 Societal Challenges Posed by Synthetic Biology
7 Concluding Remarks
Acknowledgments
References
22 Plant Systems Biology
1 Introduction
2 Network Analysis
3 Plant Systems Biology
4 Concluding Remarks
References
Index
Related Titles
Meyers, R. A. (ed.)
Encyclopedia of Molecular Cell Biology and Molecular Medicine
Online version: www.meyers-emcbmm.com
Klipp, E., Liebermeister, W.,
Wierling, C., Kowald, A., Lehrach, H., Herwig, R.
Systems Biology
A Textbook
ISBN: 978-3-527-31874-2
Fu, P., Panke, S. (eds.)
Systems Biology and Synthetic Biology
ISBN: 978-0-471-76778-7
Dehmer, M., Emmert-Streib, F. (eds.)
Analysis of Complex Networks
From Biology to Linguistics
ISBN: 978-3-527-32345-6
Junker, B. H., Schreiber, F.
Analysis of Biological Networks
ISBN: 978-0-470-04144-4
Mandoiu, I., Zelikovsky, A.
Bioinformatics Algorithms
Techniques and Applications
ISBN: 978-0-470-09773-1
The Editor
The Editor
Dr. Robert A. Meyers
Editor in Chief
RAMTECH Limited
122, Escalle Lane
Larkspur, CA 94939
USA
Cover
Network-based analysis of DNA microarray data, with kind permission by Mikael Benson (for more information see Chapter 18, Figure 5).
Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty can be created or extended by sales representatives or written sales materials. The Advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
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© 2012 Wiley-VCH Verlag & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany
Wiley-Blackwell is an imprint of John Wiley & Sons, formed by the merger of Wiley's global Scientific, Technical, and Medical business with Blackwell Publishing.
All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form — by photoprinting, microfilm, or any other means — nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.
Print ISBN: 978-3-527-32607-5
Preface and Commentary
Our project is based on the recognition that a true and complete understanding of biology and indeed, human disease must go beyond genomics. Genes and their transcripts and translation products are of course crucial, but in fact these molecules never act alone; they rather operate in tremendously complex and noisy networks. Consider it is now estimated that the human genome encodes about 20 000 to 32 000 distinct proteins, while the expression and alternative splicing of mRNAs indicates that humans may be able to produce 106 different proteins. Hence the need for the emerging discipline of Systems Biology. Thus, Systems Biology is a recently established field in life sciences that aims at promoting a global, top-down, mathematical, systems understanding of living matter through the integration of various scientific domains.
Our compendium is written for university undergraduates, graduate students, faculty and investigators at research institutes and is a team effort which began with overall guidance from our Board, which includes 11 Nobel Prize winners. Each article and author selection was then validated by several reviewers from major university research centers and each manuscript was then reviewed by peers from other universities. There is a glossary of terms with definitions provided at the beginning of each article for students and the articles average close to 30 print pages – which provides significantly more depth for advanced researchers than other systems biology reviews.
Our treatment consists of 22 articles or chapters, and begins with an overview of Systems Biology which the reader, at any level, can use as a roadmap to the content of our book. Then, the detailed articles are organized into five sections, the first of which is: the Biological Basis of Systems Biology (the chapters range from developmental biology to the Interactome and protein abundance variation); the section on Systems Biology of Evolution includes a chapter by Nobel Laureate and Board Member, Werner Arber; the Modeling of Biological Systems section includes chapters ranging from computer simulation methodology of specific systems such as the brain and cell migration as well as protein modeling. Considering that there are now about 21 000 distinct proteins encoded directly by the human genome while the expression and alternative splicing of mRNAs indicates that humans may be able to produce 106 different proteins, and we can only surmise the function of nearly half of these proteins – a systems approach is clearly needed. This section then includes top down mathematical modeling methods involving chaos, fractals, dynamics of biomolecular networks and informatics; the Systems Biology in Medicine and Disease section includes chapters on inferring networks for disease (termed the diseasome) and culminates in a chapter on systems aspects in personalized medicine for prediction and prevention. Our concluding section is Systems Biology of Organisms which includes plant systems biology as well as two chapters from scientists at the J. Craig Venter Institute, one on microbiomes which encompasses metagenomics as well as the human gut microbiome which has recently been discovered to contribute to viral infection cycles, and the other on synthetic biology which describes methods and the recent creation of a synthetic cell.
Our team hopes that you, the reader, will benefit from our hard work – finding the content useful in your research and education. We wish to thank our Managing Editor, Sarah Mellor as well as our Executive Editor, Gregor Cicchetti for both their advice and hard work in the course of this project.
Larkspur, California, March 2012
Robert A. Meyers
RAMTECH Limited
List of Contributors
Part I
Biological Basis of Systems Biology
1
Systems Biology
Melanie Boerries1, Roland Eils2, and Hauke Busch1
1Freiburg Institute for Advanced Studies – LifeNet, School of Life Sciences, Albertstraße 19, 79104 Freiburg, Germany
2German Cancer Research Institute, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
1 Introduction
2 What Is Systems Understanding?
3 Why Are Biological Systems Different?
3.1 Biological Complexity
3.2 Global Properties of Biological Systems
3.2.1 Robustness of Biological Systems
3.2.2 System Adaptation and Control
3.2.3 Modules and Protocols
4 Systems Biology Modeling
4.1 Network Biology
4.2 Dynamic Network Models
4.3 ReactionDiffusion Models
4.4 Holism versus Reductionism: The Global Dynamics of Networks
4.5 Modeling Resources and Standards
5 Future Prospects of Systems Biology
5.1 Synthetic Biology
5.2 Conclusions: Where Are We?
References
Keywords
Systems biology
A new field of biology that studies the functional structure and dynamics of intercellular and intracellular networks with the help signal- and systems-oriented methods.
Synthetic biology
Studies life as networks of biological objects such as DNA proteins RNA and metabolites.
Network biology
Studies the static organization of life as networks made up of biological entities such as DNA proteins RNA or metabolites.
System
A set of interacting parts functioning as a whole and distinguishable from its surroundings by identifiable boundaries.
Systems theory
This denotes the cross-disciplinary investigation of the abstract organization of systems irrespective of their substance type or spatiotemporal scale of existence. The goal is the study of emerging properties that arise from the interconnectedness of the individual parts making up the system.
Robustness
The robustness of biological systems denotes the maintenance of specific system functionalities in the presence of fluctuations or change in environmental parameters.
Control
Control is defined as the response action taken by a system to counteract parameter changes to maintain system functions at a certain predefined level.
Modularity
A design concept of complex systems to integrate simpler self-contained functional building-blocks into the framework of one larger system.
Model
The concept of representing causal relationships from real systems in the language of mathematics
Systems Biology is a new field of biology, which places the theoretical foundations of systems analysis of living matter into the context of modern high-throughput quantitative experimental data, mathematics, and in silico simulations. The aim is to analyze the organization and to gain engineering-control of metabolic and genetic pathways. The ultimate goal is to gain an “holistic” view of the complex workings of life. The need for a system level understanding of biology is reviewed in this chapter, and comments are provided on the current scientific progress in this field. The current and future directions of experimental design strategies and theoretical approaches are also highlighted.
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