Handbook of Systems Biology

List of Contributors

Preface

Reviewers

Section I: Components of Biological Systems

Chapter 1. Proteomic Analysis of Cellular Systems

Introduction

MS-Based Proteomics Workflow

Computational Proteomics

Deep Expression Proteomics

Interaction Proteomics

Large-Scale Determination of Post-Translational Modifications

Outlook and Future Challenges

References

Chapter 2. The Coding and the Non-coding Transcriptome

Introduction

The Pathway from DNA to Protein Sequences

Methods to Determine the Reference Transcriptome

The Human Transcriptome

Conclusions and Future Challenges

References

Section II: Network Properties of Biological Systems

Chapter 3. Interactome Networks

Introduction

Towards a Reference Protein–Protein Interactome Map

Drawing Inferences from Interactome Networks

Towards Dynamic Interactomes

Concluding Remarks

Acknowledgements

References

Chapter 4. Gene Regulatory Networks

Cells are Computers

Gene Regulation

Transcription

Gene Regulatory Networks (GRNs)

Future Challenges

Acknowledgements

References

Chapter 5. Analyzing the Structure, Function and Information Flow in Signaling Networks using Quantitative Cellular Signatures

The Concept of Linear Cassettes and Modularity in Signal Transduction

Genetic Dissection of Signal Transduction Pathways

Systems Approaches to Identify the ‘Parts’ of Cellular Signaling Networks

Quantitative RNAi Signatures or Phenoprints to Infer Context Dependent Information Flow Through Cellular Signaling Networks

Concluding Remarks

References

Chapter 6. Genetic Networks

Introduction

Defining Genetic Interactions

Experimental Approaches to Map Genetic Interaction Networks in Yeast

Exploring Genetic Interaction Networks

Integrating Genetic Interactions with Other Biological Networks

Mapping Genetic Interactions in Other Organisms

Genetic Network Conservation

Expanding Genetic Networks: Mutant Alleles, Conditions and Phenotypes

Genetic Interactions and Genome-Wide Association Studies

Acknowledgements

References

Chapter 7. The Spatial Architecture of Chromosomes

Introduction

The Basic Material: the Chromatin Fiber

The Polymer Physics of Chromosomes

Nuclear Confinement and Formation of Chromosome Territories

Anchoring of the Genome to Fixed Scaffolds

The Internal Organization of Chromosomes: Long-Range Interactions Along and Between Chromosomes

A Stochastic Interaction-Driven Model for Genome Folding and Nuclear Organization

Future Challenges

References

Chapter 8. Chemogenomic Profiling: Understanding the Cellular Response to Drug

Impact of the Human Genome Project on Healthcare and Biology

Impact of Genomics: Shifting the Perceptions of Drug and Cellular Behavior

Chemogenomics

HIPHOP

Conclusions and Future Challenges

References

Chapter 9. Graph Theory Properties of Cellular Networks

Introduction

Biological Systems as Graphs

The Tools of Graph Theory

Successes and Failures of the Erdős–Rényi Model

Scale-Free Nature of Cellular Networks

Hierarchy and Modularity

Party vs. Date Hubs

Degree Correlations

Human Disease Network

The Building Blocks of Cellular Networks

Going Beyond Topology

From Structure to Dynamics

References

Section III: Dynamic and Logical Properties of Biological Systems

Chapter 10. Boolean Models of Cellular Signaling Networks

Introduction

Boolean Networks and Biological Systems

Boolean Network Modeling

Application Examples

Conclusions and Future Directions

References

Chapter 11. Transcriptional Network Logic: The Systems Biology of Development

Development is a System-Wide Direct Output of the Genome

GRN Structural Components and Model Representation

The Regulatory State Concept

System-Wide and Deep Information Flow in Development

General Features of the Developmental Process

Developmental GRN Dynamics

Examples of GRN-Mediated Spatial Control in Development

Conclusion: The Explanation of Development

Note Added in Proof

Acknowledgement

References

Chapter 12. Reconstruction of Genome-Scale Metabolic Networks

Introduction

The Reconstruction Process

Reconstruction Standards

Applications

Future Directions

Glossary

Acknowledgments

References

Chapter 13. Genotype Networks and Evolutionary Innovations in Biological Systems

Introduction

Metabolic Networks and Their Innovations

Regulatory Circuits and Their Innovations

Macromolecules and Their Innovations

Towards a Systematic Understanding of Innovation

Genotype Spaces and the Phenotypes Therein

References

Chapter 14. Irreversible Transitions, Bistability and Checkpoint Controls in the Eukaryotic Cell Cycle: A Systems-Level Understanding

Introduction

Irreversibility and Bistability

Irreversible Transitions in the Budding Yeast Cell Cycle

Irreversible Transitions in the Mammalian Cell Cycle

Additional Checkpoints

Conclusions

References

Chapter 15. Phenotypes and Design Principles in System Design Space

Background

Phenotypes

Design Principles

Conclusions and Future Challenges

Acknowledgements

References

Chapter 16. System Biology of Cell Signaling

Introduction

Cellular Signaling: Pathways to Networks

Isoforms of Signaling Molecules, Signaling Integration and Sorting

Scaffolding Proteins: Signaling Networks Form Signaling Complexes

Computational Analysis of Signaling Networks

Regulation By Network Motifs

Properties of a Cellular Signaling Network

Network Topology and Consolidation of Signals

Dynamical Models

Positive Feedback Loops can form Switches: The Concept of Bistability

Signaling Microdomains Within Cells

Conclusions and Future Challenges

Glossary

Acknowledgments

References

Chapter 17. Spatial Organization of Subcellular Systems

Motivation

Dimensionality Effects in Biochemical Reactions

Towards a Systemic Understanding of Cellular Biology

Spatiotemporal Modeling of Cellular Processes

Spatiotemporal Quantification of Cellular Processes

Causality From Variation and Perturbation Analysis

Model-Driven Experimentation and Experimentally Driven Modeling

Conclusions

References

Section IV: Systems and Biology

Chapter 18. Yeast Systems Biology: Towards a Systems Understanding of Regulation of Eukaryotic Networks in Complex Diseases and Biotechnology

Introduction

Yeast for Systems Understanding of Eukaryotic Biology and Networks Applications

Conclusions: Future Perspectives

Acknowledgements

References

Chapter 19. Systems Biology of Caenorhabditis elegans

Introduction: The System before the Sequence

Forward and Reverse Genetics in the Worm: How 97mb says ‘Make a Worm’

Expressing and Regulating an Animal Genome

Integrative and Dynamic Modeling to Link Genotype to Phenotype

Outlook

References

Chapter 20. Arabidopsis as a Model for Systems Biology

Introduction

Systems Analysis of Arabidopsis Development

Development and the Response to Environmental Stress

Conclusions and Perspective

References

Chapter 21. The Role of the Circadian System in Homeostasis

Introduction

Evolution of Clocks

Role of the clock in neurological functions

Homeostasis: You Notice It When It’s Broken

Clocks in Energy and Metabolic Homeostasis

Conclusion

References

Chapter 22. Biological and Quantitative Models for Stem Cell Self-Renewal and Differentiation

Current Problems and Paradigms in Stem Cell Research

Examples of Quantitative Models Explaining Stem Cell Behavior

Strategies for Model Construction and Validation

Information Flow and Epigenetic Landscapes in Differentiation

References

Section V: Multi-Scale Biological Systems, Health and Ecology

Chapter 23. Systems Medicine and the Emergence of Proactive P4 Medicine: Predictive, Preventive, Personalized and Participatory

Introduction

Systems Medicine

Five Systems’ Strategies for Dealing with Biological Complexity

P4 Medicine

Two Big Challenges: Education and Information Technology for Healthcare

Impact of P4 Medicine on Society

How to Bring P4 Medicine to Patients

Acknowledgments

References

Chapter 24. Cancer Systems Biology: A Robustness-Based Approach

Introduction

Mechanisms for Robustness

Mechanisms for Cancer Robustness

Robustness Trade-offs

Theoretically Motivated Therapy Strategies

A Proper Index of Treatment Efficacy

Long-Tail Drug

Open Pharma

Conclusion

Acknowledgements

References

Chapter 25. Systems Immunology: From Cells and Molecules to a Dynamic Multi-Scale System

Introduction

Cell-Focused Systems Immunology

System-Focused Systems Immunology

Multi-Scale-Focused Systems Immunology

Conclusions and Future Challenges

References

Chapter 26. Causal Inference and the Construction of Predictive Network Models in Biology

Introduction

A Movie Analogy for Modeling Biological Systems

Causality as A Statistical Inference

From Assessing Causal Relationships Among Trait Pairs to Predictive Gene Networks

Conclusion and Future Directions

References

Chapter 27. Social Networks, Contagion Processes and the Spreading of Infectious Diseases

Introduction

Network Thinking

Contagion Phenomena in Complex Social Networks

Complex Networks and the Large-Scale Spreading of Infectious Diseases

Conclusions and Future Challenges

References

Index