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Chapter 1 Introduction to Protein Complex Prediction 1

1.1 From Protein Interactions to Protein Complexes 6

1.2 Databases for Protein Complexes 11

1.3 Organization of the Rest of the Book 13

Chapter 2 Constructing Reliable Protein-Protein Interaction （PPI） Networks 15

2.1 High-Throughput Experimental Systems to Infer PPIs 15

2.2 Data Sources for PPIs 23

2.3 Topological Properties of PPI Networks 25

2.4 Theoretical Models for PPI Networks 27

2.5 Visualizing PPI Networks 31

2.6 Building High-Confidence PPI Networks 34

2.7 Enhancing PPI Networks by Integrating Functional Interactions 50

Chapter 3 Computational Methods for Protein Complex Prediction from PPI Networks 59

3.1 Basic Definitions and Terminologies 60

3.2 Taxonomy of Methods for Protein Complex Prediction 60

3.3 Methods Based Solely on PPI Network Clustering 61

3.4 Methods Incorporating Core-Attachment Structure 78

3.5 Methods Incorporating Functional Information 85

Chapter 4 Evaluating Protein Complex Prediction Methods 91

4.1 Evaluation Criteria and Methodology 91

4.2 Evaluation on Unweighted Yeast PPI Networks 93

4.3 Evaluation on Weighted Yeast PPI Networks 95

4.4 Evaluation on Human PPI Networks 99

4.5 Case Study：Prediction of the Human Mechanistic Target of Rapamycin Complex 103

4.6 Take-Home Lessons from Evaluating Prediction Methods 105

Chapter 5 Open Challenges in Protein Complex Prediction 107

5.1 Three Main Challenges in Protein Complex Prediction 107

5.2 Identifying Sparse Protein Complexes 112

5.3 Identifying Overlapping Protein Complexes 118

5.4 Identifying Small Protein Complexes 124

5.5 Identifying Protein Sub-complexes 134

5.6 An Integrated System for Identifying Challenging Protein Complexes 136

5.7 Recent Methods for Protein Complex Prediction 138

5.8 Identifying Membrane-Protein Complexes 141

Chapter 6 Identifying Dynamic Protein Complexes 145

6.1 Dynamism of Protein Interactions and Protein Complexes 145

6.2 Identifying Temporal Protein Complexes 149

6.3 Intrinsic Disorder in Proteins 156

6.4 Intrinsic Disorder in Protein Interactions and Protein Complexes 157

6.5 Identifying Fuzzy Protein Complexes 162

Chapter 7 Identifying Evolutionarily Conserved Protein Complexes 165

7.1 Inferring Evolutionarily Conserved PPIs （Interologs） 166

7.2 Identifying Conserved Complexes from Interolog Networks，Ⅰ 170

7.3 Identifying Conserved Complexes from Interolog Networks，Ⅱ 178

Chapter 8 Protein Complex Prediction in the Era of Systems Biology 185

8.1 Constructing the Network of Protein Complexes 185

8.2 Identifying Protein Complexes Across Phenotypes 189

8.3 Identifying Protein Complexes in Diseases 192

8.4 Enhancing Quantitative Proteomics Using PPI Networks and Protein Complexes 208

8.5 Systems Biology Tools and Databases to Analyze Biomolecular Networks 221

Chapter 9 Conclusion 225

References 233

Authors’ Biographies 279