Analysis of Biological Networks

Preface xv

Contributors xix

PART I INTRODUCTION 1

1 Networks in Biology 3
Bjorn H. Junker

1.1 Introduction 3

1.2 Biology 101 4

1.3 Systems Biology 8

1.4 Properties of Biological Networks 8

1.5 Summary 12

1.6 Exercises 12

2 Graph Theory 15
Falk Schreiber

2.1 Introduction 15

2.2 Basic Notation 16

2.3 Special Graphs 19

2.4 Graph Representation 23

2.5 Graph Algorithms 24

2.6 Summary 27

2.7 Exercises 27

PART II NETWORK ANALYSIS 29

3 Global Network Properties 31
Ralf Steuer and Gorka Zamora Lopez

3.1 Introduction 31

3.2 Global Properties of Complex Networks 33

3.3 Models of Complex Networks 43

3.4 Additional Properties of Complex Networks 48

3.5 Statistical Testing of Network Properties 52

3.6 Summary 57

3.7 Exercises 58

4 Network Centralities 65
Dirk Koschutzki

4.1 Introduction 65

4.2 Centrality Definition and Fundamental Properties 67

4.3 Degree and Shortest Path-Based Centralities 69

4.4 Feedback-Based Centralities 77

4.5 Tools 80

4.6 Summary 80

4.7 Exercises 81

5 Network Motifs 85
Henning Schwobbermeyer

5.1 Introduction 85

5.2 Definitions and Basic Concepts 86

5.3 Motif Statistics and Motif-Based Network Distance 89

5.4 Complexity of Network Motif Detection 94

5.5 Methods and Tools for Network Motif Analysis 96

5.6 Analyses and Applications of Network Motifs 97

5.7 Summary 106

5.8 Exercises 108

6 Network Clustering 113
Balabhaskar Balasundaram and Sergiy Butenko

6.1 Introduction 113

6.2 Notations and Definitions 115

6.3 Network Clustering Problem 118

6.4 Clique-Based Clustering 119

6.5 Center-Based Clustering 125

6.6 Conclusion 131

6.7 Summary 133

6.8 Exercises 133

7 Petri Nets 139
Ina Koch and Monika Heiner

7.1 Introduction 139

7.2 Qualitative Modeling 141

7.3 Qualitative Analysis 152

7.4 Quantitative Modeling and Analysis 169

7.5 Tool Support 171

7.6 Case Studies 172

7.7 Summary 174

7.8 Exercises 175

PART III BIOLOGICAL NETWORKS 181

8 Signal Transduction and Gene Regulation Networks 183
Anatolij P. Potapov

8.1 Introduction 183

8.2 Decisive Role of Regulatory Networks in the Evolution and Existence of Organisms 184

8.3 Gene Regulatory Network as a System of Many Subnetworks 186

8.4 Databases on Gene Regulation and Software Tools for Network Analysis 187

8.5 Peculiarities of Signal Transduction Networks 188

8.6 Topology of Signal Transduction Networks 190

8.7 Topology of Transcription Networks 191

8.8 Intercellular Molecular Regulatory Networks 198

8.9 Summary 200

8.10 Exercises 201

9 Protein Interaction Networks 207
Frederik Bornke

9.1 Introduction 207

9.2 Detecting Protein Interactions 209

9.3 Establishing Protein Interaction Networks 220

9.4 Analyzing Protein Interaction Networks 223

9.5 Summary 225

9.6 Exercises 226

10 Metabolic Networks 233
Marcio Rosa da Silva, Jibin Sun, Hongwu Ma, Feng He, and An-Ping Zeng

10.1 Introduction 233

10.2 Visualization and Graph Representation 234

10.3 Reconstruction of Genome-Scale Metabolic Networks 234

10.4 Connectivity and Centrality in Metabolic Networks 239

10.5 Modularity and Decomposition of Metabolic Networks 242

10.6 Elementary Flux Modes and Extreme Pathways 246

10.7 Summary 249

10.8 Exercises 249

11 Phylogenetic Networks 255
Birgit Gemeinholzer

11.1 Introduction 255

11.2 Character Selection, Character Coding, and Matrices for Phylogenetic Reconstruction 257

11.3 Tree Reconstruction Methodologies 260

11.4 Phylogenetic Networks 264

11.5 Summary 276

11.6 Exercises 276

12 Ecological Networks 283
Ursula Gaedke

12.1 Introduction 283

12.2 Binary Food Webs 289

12.3 Quantitative Trophic Food Webs 293

12.4 Ecological Information Networks 298

12.5 Summary 300

12.6 Exercises 301

13 Correlation Networks 305
Dirk Steinhauser, Leonard Krall, Carsten Mussig, Dirk Bussis, and Bjorn Usadel

13.1 Introduction 305

13.2 General Remarks 306

13.3 Basic Notation 307

13.4 Construction and Analyses of Correlation Networks 314

13.5 Biological Use of Correlation Networks 321

13.6 Summary 328

13.7 Exercises 329

References 330

Index 335