Preface of the First Edition |
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xv | |
Preface of the Second Edition |
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xvii | |
1 Networks in Biological Cells |
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1 | (20) |
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1.1 Some Basics About Networks |
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1 | (3) |
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2 | (1) |
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1.1.2 Small-World Phenomenon |
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2 | (1) |
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1.1.3 Scale-Free Networks |
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3 | (1) |
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1.2 Biological Background |
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4 | (4) |
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1.2.1 Transcriptional Regulation |
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5 | (1) |
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1.2.2 Cellular Components |
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5 | (2) |
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1.2.3 Spatial Organization of Eukaryotic Cells into Compartments |
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7 | (1) |
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1.2.4 Considered Organisms |
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8 | (1) |
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8 | (4) |
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1.3.1 Biochemical Pathways |
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8 | (3) |
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1.3.2 Enzymatic Reactions |
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11 | (1) |
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1.3.3 Signal Transduction |
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11 | (1) |
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12 | (1) |
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1.4 Ontologies and Databases |
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12 | (5) |
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12 | (1) |
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13 | (1) |
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1.4.3 Kyoto Encyclopedia of Genes and Genomes |
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13 | (1) |
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13 | (1) |
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14 | (1) |
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14 | (1) |
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15 | (1) |
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1.4.8 Systems Biology Markup Language |
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15 | (2) |
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1.5 Methods for Cellular Modeling |
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17 | (1) |
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17 | (1) |
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17 | (1) |
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18 | (3) |
2 Structures of Protein Complexes and Subcellular Structures |
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21 | (42) |
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2.1 Examples of Protein Complexes |
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22 | (6) |
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2.1.1 Principles of Protein-Protein Interactions |
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24 | (3) |
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2.1.2 Categories of Protein Complexes |
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27 | (1) |
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2.2 Complexome: The Ensemble of Protein Complexes |
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28 | (3) |
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2.2.1 Complexome of Saccharomyces cerevisiae |
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28 | (2) |
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2.2.2 Bacterial Protein Complexomes |
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30 | (1) |
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2.2.3 Complexome of Human |
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31 | (1) |
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2.3 Experimental Determination of Three-Dimensional Structures of Protein Complexes |
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31 | (7) |
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2.3.1 X-ray Crystallography |
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32 | (2) |
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34 | (1) |
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2.3.3 Electron Crystallography/Electron Microscopy |
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34 | (1) |
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34 | (1) |
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2.3.5 Immunoelectron Microscopy |
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35 | (1) |
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2.3.6 Fluorescence Resonance Energy Transfer |
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35 | (1) |
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36 | (2) |
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38 | (2) |
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2.4.1 Correlation-Based Density Fitting |
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38 | (2) |
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2.5 Fourier Transformation |
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40 | (4) |
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40 | (1) |
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2.5.2 Continuous Fourier Transform |
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41 | (1) |
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2.5.3 Discrete Fourier Transform |
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41 | (1) |
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2.5.4 Convolution Theorem |
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41 | (1) |
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2.5.5 Fast Fourier Transformation |
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42 | (2) |
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2.6 Advanced Density Fitting |
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44 | (2) |
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45 | (1) |
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2.7 FFT Protein-Protein Docking |
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46 | (2) |
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2.8 Protein-Protein Docking Using Geometric Hashing |
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48 | (1) |
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2.9 Prediction of Assemblies from Pairwise Docking |
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49 | (4) |
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49 | (3) |
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52 | (1) |
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52 | (1) |
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53 | (3) |
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2.10.1 Reconstruction of Phantom Cell |
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55 | (1) |
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2.10.2 Protein Complexes in Mycoplasma pneumoniae |
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55 | (1) |
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56 | (1) |
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57 | (3) |
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2.12.1 Mapping of Crystal Structures into EM Maps |
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57 | (3) |
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60 | (3) |
3 Analysis of Protein-Protein Binding |
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63 | (26) |
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63 | (3) |
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3.2 Properties of Protein-Protein Interfaces |
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66 | (9) |
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66 | (2) |
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3.2.2 Composition of Binding Interfaces |
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68 | (1) |
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69 | (2) |
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3.2.4 Physicochemical Properties of Protein Interfaces |
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71 | (1) |
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3.2.5 Predicting Binding Affinities of Protein-Protein Complexes |
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72 | (1) |
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3.2.6 Forces Important for Biomolecular Association |
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73 | (2) |
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3.3 Predicting Protein-Protein Interactions |
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75 | (11) |
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3.3.1 Pairing Propensities |
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75 | (3) |
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3.3.2 Statistical Potentials for Amino Acid Pairs |
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78 | (1) |
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3.3.3 Conservation at Protein Interfaces |
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79 | (4) |
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3.3.4 Correlated Mutations at Protein Interfaces |
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83 | (3) |
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86 | (1) |
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86 | (1) |
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86 | (3) |
4 Algorithms on Mathematical Graphs |
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89 | (22) |
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4.1 Primer on Mathematical Graphs |
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89 | (1) |
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4.2 A Few Words About Algorithms and Computer Programs |
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90 | (3) |
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4.2.1 Implementation of Algorithms |
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91 | (1) |
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4.2.2 Classes of Algorithms |
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92 | (1) |
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4.3 Data Structures for Graphs |
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93 | (2) |
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95 | (6) |
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4.4.1 Description of the Algorithm |
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96 | (4) |
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100 | (1) |
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101 | (1) |
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4.5 Minimum Spanning Tree |
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101 | (1) |
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4.5.1 Kruskal's Algorithm |
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102 | (1) |
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102 | (2) |
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104 | (1) |
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105 | (5) |
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4.8.1 Force Directed Layout of Graphs |
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107 | (3) |
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110 | (1) |
5 Protein-Protein Interaction Networks - Pairwise Connectivity |
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111 | (30) |
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5.1 Experimental High-Throughput Methods for Detecting Protein-Protein Interactions |
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111 | (9) |
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5.1.1 Gel Electrophoresis |
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112 | (1) |
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5.1.2 Two-Dimensional Gel Electrophoresis |
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112 | (1) |
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5.1.3 Affinity Chromatography |
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113 | (1) |
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5.1.4 Yeast Two-hybrid Screening |
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114 | (1) |
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5.1.5 Synthetic Lethality |
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115 | (1) |
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116 | (1) |
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5.1.7 Databases for Interaction Networks |
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116 | (1) |
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5.1.8 Overlap of Interactions |
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116 | (2) |
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5.1.9 Criteria to Judge the Reliability of Interaction Data |
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118 | (2) |
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5.2 Bioinformatic Prediction of Protein-Protein Interactions |
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120 | (4) |
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5.2.1 Analysis of Gene Order |
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121 | (1) |
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5.2.2 Phylogenetic Profiling/Coevolutionary Profiling |
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121 | (3) |
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122 | (2) |
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5.3 Bayesian Networks for Judging the Accuracy of Interactions |
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124 | (7) |
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125 | (1) |
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125 | (1) |
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5.3.3 Application of Bayesian Networks to Protein-Protein Interaction Data |
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126 | (5) |
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5.3.3.1 Measurement of Reliability "Likelihood Ratio" |
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127 | (1) |
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5.3.3.2 Prior and Posterior Odds |
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127 | (1) |
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5.3.3.3 A Worked Example: Parameters of the Naive Bayesian Network for Essentiality |
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128 | (1) |
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5.3.3.4 Fully Connected Experimental Network |
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129 | (2) |
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5.4 Protein Interaction Networks |
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131 | (1) |
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5.4.1 Protein Interaction Network of Saccharomyces cerevisiae |
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131 | (1) |
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5.4.2 Protein Interaction Network of Escherichia coli |
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131 | (1) |
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5.4.3 Protein Interaction Network of Human |
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132 | (1) |
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5.5 Protein Domain Networks |
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132 | (3) |
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135 | (1) |
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136 | (2) |
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5.7.1 Bayesian Analysis of (Fake) Protein Complexes |
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136 | (2) |
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138 | (3) |
6 Protein-Protein Interaction Networks - Structural Hierarchies |
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141 | (40) |
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6.1 Protein Interaction Graph Networks |
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141 | (4) |
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6.1.1 Degree Distribution |
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141 | (2) |
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6.1.2 Clustering Coefficient |
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143 | (2) |
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145 | (1) |
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146 | (1) |
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147 | (2) |
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6.5 Detecting Communities in Networks |
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149 | (6) |
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6.5.1 Divisive Algorithms for Mapping onto Tree |
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153 | (2) |
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6.6 Modular Decomposition |
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155 | (6) |
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6.6.1 Modular Decomposition of Graphs |
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157 | (4) |
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6.7 Identification of Protein Complexes |
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161 | (4) |
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161 | (1) |
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162 | (1) |
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163 | (1) |
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6.7.4 Analysis of Target Gene Coexpression |
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164 | (1) |
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6.8 Network Growth Mechanisms |
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165 | (4) |
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169 | (1) |
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169 | (9) |
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178 | (3) |
7 Protein-DNA Interactions |
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181 | (16) |
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7.1 Transcription Factors |
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181 | (2) |
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7.2 Transcription Factor-Binding Sites |
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183 | (1) |
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7.3 Experimental Detection of TFBS |
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183 | (4) |
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7.3.1 Electrophoretic Mobility Shift Assay |
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183 | (1) |
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184 | (1) |
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7.3.3 Protein-Binding Microarrays |
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185 | (2) |
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7.3.4 Chromatin Immunoprecipitation Assays |
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187 | (1) |
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7.4 Position-Specific Scoring Matrices |
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187 | (2) |
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7.5 Binding Free Energy Models |
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189 | (2) |
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7.6 Cis-Regulatory Motifs |
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191 | (1) |
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192 | (1) |
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7.7 Relating Gene Expression to Binding of Transcription Factors |
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192 | (2) |
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194 | (1) |
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194 | (1) |
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195 | (2) |
8 Gene Expression and Protein Synthesis |
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197 | (30) |
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8.1 Regulation of Gene Transcription at Promoters |
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197 | (1) |
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8.2 Experimental Analysis of Gene Expression |
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198 | (3) |
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8.2.1 Real-time Polymerase Chain Reaction |
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199 | (1) |
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8.2.2 Microarray Analysis |
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199 | (2) |
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201 | (1) |
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201 | (6) |
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203 | (1) |
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203 | (1) |
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8.3.3 Fisher's Exact Test |
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203 | (2) |
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8.3.4 Mann-Whitney-Wilcoxon Rank Sum Tests |
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205 | (1) |
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8.3.5 Kolmogorov-Smirnov Test |
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206 | (1) |
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8.3.6 Hypergeometric Test |
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206 | (1) |
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8.3.7 Multiple Testing Correction |
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207 | (1) |
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8.4 Preprocessing of Data |
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207 | (2) |
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8.4.1 Removal of Outlier Genes |
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207 | (1) |
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8.4.2 Quantile Normalization |
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208 | (1) |
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208 | (1) |
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8.5 Differential Expression Analysis |
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209 | (5) |
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210 | (1) |
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8.5.2 SAM Analysis of Microarray Data |
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210 | (2) |
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8.5.3 Differential Expression Analysis of RNA-seq Data |
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212 | (2) |
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8.5.3.1 Negative Binomial Distribution |
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213 | (1) |
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213 | (1) |
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214 | (3) |
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8.6.1 Functional Enrichment |
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216 | (1) |
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8.7 Similarity of GO Terms |
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217 | (1) |
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8.8 Translation of Proteins |
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217 | (2) |
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8.8.1 Transcription and Translation Dynamics |
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218 | (1) |
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219 | (1) |
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220 | (4) |
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224 | (3) |
9 Gene Regulatory Networks |
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227 | (30) |
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9.1 Gene Regulatory Networks (GRNs) |
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228 | (3) |
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9.1.1 Gene Regulatory Network of E. coli |
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228 | (3) |
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9.1.2 Gene Regulatory Network of S. cerevisiae |
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231 | (1) |
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9.2 Graph Theoretical Models |
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231 | (3) |
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9.2.1 Coexpression Networks |
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232 | (1) |
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233 | (1) |
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234 | (4) |
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234 | (1) |
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9.3.2 Reverse Engineering Boolean Networks |
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235 | (1) |
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9.3.3 Differential Equations Models |
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236 | (2) |
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9.4 DREAM: Dialogue on Reverse Engineering Assessment and Methods |
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238 | (6) |
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239 | (1) |
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9.4.2 YAYG Approach in DREAM3 Contest |
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240 | (4) |
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244 | (3) |
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9.5.1 Feed-forward Loop (FFL) |
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245 | (1) |
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245 | (1) |
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9.5.3 Densely Overlapping Region (DOR) |
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246 | (1) |
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9.6 Algorithms on Gene Regulatory Networks |
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247 | (3) |
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9.6.1 Key-pathway Miner Algorithm |
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247 | (1) |
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9.6.2 Identifying Sets of Dominating Nodes |
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248 | (1) |
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9.6.3 Minimum Dominating Set |
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249 | (1) |
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9.6.4 Minimum Connected Dominating Set |
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249 | (1) |
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250 | (1) |
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251 | (3) |
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254 | (3) |
10 Regulatory Noncoding RNA |
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257 | (16) |
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10.1 Introduction to RNAs |
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257 | (2) |
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10.2 Elements of RNA Interference: siRNAs and miRNAs |
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259 | (2) |
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261 | (3) |
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10.4 Predicting miRNA Targets |
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264 | (1) |
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10.5 Role of TFs and miRNAs in Gene-Regulatory Networks |
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264 | (2) |
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10.6 Constructing TF/miRNA Coregulatory Networks |
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266 | (4) |
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267 | (6) |
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10.6.1.1 Construction of Candidate TF-miRNA-Gene FFLs |
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268 | (1) |
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269 | (1) |
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270 | (1) |
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270 | (3) |
11 Computational Epigenetics |
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273 | (30) |
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11.1 Epigenetic Modifications |
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273 | (8) |
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273 | (4) |
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276 | (1) |
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277 | (1) |
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11.1.3 Chromatin-Regulating Enzymes |
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278 | (1) |
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11.1.4 Measuring DNA Methylation Levels and Histone Marks Experimentally |
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279 | (2) |
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11.2 Working with Epigenetic Data |
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281 | (5) |
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11.2.1 Processing of DNA Methylation Data |
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281 | (1) |
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11.2.1.1 Imputation of Missing Values |
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281 | (1) |
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11.2.1.2 Smoothing of DNA Methylation Data |
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281 | (1) |
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11.2.2 Differential Methylation Analysis |
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282 | (1) |
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11.2.3 Comethylation Analysis |
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283 | (2) |
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11.2.4 Working with Data on Histone Marks |
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285 | (1) |
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286 | (6) |
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11.3.1 Measuring Chromatin States |
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286 | (1) |
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11.3.2 Connecting Epigenetic Marks and Gene Expression by Linear Models |
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287 | (1) |
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11.3.3 Markov Models and Hidden Markov Models |
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288 | (2) |
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11.3.4 Architecture of a Hidden Markov Model |
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290 | (1) |
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11.3.5 Elements of an HMM |
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291 | (1) |
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11.4 The Role of Epigenetics in Cellular Differentiation and Reprogramming |
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292 | (3) |
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11.4.1 Short History of Stem Cell Research |
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293 | (1) |
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11.4.2 Developmental Gene Regulatory Networks |
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293 | (2) |
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11.5 The Role of Epigenetics in Cancer and Complex Diseases |
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295 | (1) |
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296 | (1) |
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296 | (5) |
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301 | (2) |
12 Metabolic Networks |
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303 | (46) |
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303 | (3) |
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12.2 Resources on Metabolic Network Representations |
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306 | (2) |
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12.3 Stoichiometric Matrix |
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308 | (1) |
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12.4 Linear Algebra Primer |
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309 | (5) |
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12.4.1 Matrices: Definitions and Notations |
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309 | (1) |
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12.4.2 Adding, Subtracting, and Multiplying Matrices |
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310 | (1) |
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12.4.3 Linear Transformations, Ranks, and Transpose |
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311 | (1) |
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12.4.4 Square Matrices and Matrix Inversion |
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311 | (1) |
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12.4.5 Eigenvalues of Matrices |
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312 | (1) |
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12.4.6 Systems of Linear Equations |
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313 | (1) |
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12.5 Flux Balance Analysis |
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314 | (5) |
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12.5.1 Gene Knockouts: MOMA Algorithm |
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316 | (2) |
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12.5.2 OptKnock Algorithm |
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318 | (1) |
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12.6 Double Description Method |
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319 | (5) |
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12.7 Extreme Pathways and Elementary Modes |
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324 | (8) |
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12.7.1 Steps of the Extreme Pathway Algorithm |
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324 | (4) |
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12.7.2 Analysis of Extreme Pathways |
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328 | (1) |
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12.7.3 Elementary Flux Modes |
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329 | (2) |
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12.7.4 Pruning Metabolic Networks: NetworkReducer |
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331 | (1) |
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332 | (7) |
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12.8.1 Applications of Minimal Cut Sets |
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337 | (2) |
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339 | (2) |
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341 | (1) |
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341 | (5) |
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12.11.1 Static Network Properties: Pathways |
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341 | (5) |
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346 | (3) |
13 Kinetic Modeling of Cellular Processes |
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349 | (26) |
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13.1 Biological Oscillators |
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349 | (1) |
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350 | (3) |
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13.2.1 Role of Post-transcriptional Modifications |
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352 | (1) |
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13.3 Ordinary Differential Equation Models |
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353 | (3) |
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354 | (2) |
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13.4 Modeling Cellular Feedback Loops by ODEs |
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356 | (10) |
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13.4.1 Protein Synthesis and Degradation: Linear Response |
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356 | (1) |
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13.4.2 Phosphorylation/Dephosphorylation - Hyperbolic Response |
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357 | (2) |
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13.4.3 Phosphorylation/Dephosphorylation - Buzzer |
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359 | (1) |
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13.4.4 Perfect Adaptation - Sniffer |
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360 | (1) |
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13.4.5 Positive Feedback - One-Way Switch |
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361 | (1) |
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13.4.6 Mutual Inhibition - Toggle Switch |
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362 | (1) |
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13.4.7 Negative Feedback - Homeostasis |
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362 | (2) |
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13.4.8 Negative Feedback: Oscillatory Response |
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364 | (1) |
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13.4.9 Cell Cycle Control System |
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365 | (1) |
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13.5 Partial Differential Equations |
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366 | (3) |
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13.5.1 Spatial Gradients of Signaling Activities |
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368 | (1) |
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13.5.2 Reaction-Diffusion Systems |
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368 | (1) |
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13.6 Dynamic Phosphorylation of Proteins |
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369 | (1) |
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370 | (2) |
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372 | (1) |
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373 | (2) |
14 Stochastic Processes in Biological Cells |
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375 | (34) |
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14.1 Stochastic Processes |
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375 | (3) |
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14.1.1 Binomial Distribution |
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376 | (1) |
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377 | (1) |
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377 | (1) |
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14.2 Dynamic Monte Carlo (Gillespie Algorithm) |
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378 | (2) |
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14.2.1 Basic Outline of the Gillespie Method |
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379 | (1) |
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14.3 Stochastic Effects in Gene Transcription |
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380 | (5) |
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14.3.1 Expression of a Single Gene |
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380 | (1) |
|
|
381 | (4) |
|
14.4 Stochastic Modeling of a Small Molecular Network |
|
|
385 | (7) |
|
14.4.1 Model System: Bacterial Photosynthesis |
|
|
385 | (1) |
|
14.4.2 Pools-and-Proteins Model |
|
|
386 | (1) |
|
14.4.3 Evaluating the Binding and Unbinding Kinetics |
|
|
387 | (2) |
|
14.4.4 Pools of the Chromatophore Vesicle |
|
|
389 | (1) |
|
14.4.5 Steady-State Regimes of the Vesicle |
|
|
389 | (3) |
|
14.5 Parameter Optimization with Genetic Algorithm |
|
|
392 | (3) |
|
14.6 Protein-Protein Association |
|
|
395 | (1) |
|
14.7 Brownian Dynamics Simulations |
|
|
396 | (2) |
|
|
398 | (2) |
|
|
400 | (7) |
|
14.9.1 Dynamic Simulations of Networks |
|
|
400 | (7) |
|
|
407 | (2) |
15 Integrated Cellular Networks |
|
409 | (18) |
|
15.1 Response of Gene Regulatory Network to Outside Stimuli |
|
|
410 | (2) |
|
15.2 Whole-Cell Model of Mycoplasma genitalium |
|
|
412 | (4) |
|
15.3 Architecture of the Nuclear Pore Complex |
|
|
416 | (1) |
|
15.4 Integrative Differential Gene Regulatory Network for Breast Cancer Identified Putative Cancer Driver Genes |
|
|
416 | (5) |
|
15.5 Particle Simulations |
|
|
421 | (2) |
|
|
423 | (1) |
|
|
424 | (3) |
16 Outlook |
|
427 | (2) |
Index |
|
429 | |