Preface |
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xvii | |
Contributors |
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xix | |
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A METHODOLOGICAL CHAPTERS |
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1 | (132) |
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1 Two Challenges of Systems Biology |
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3 | (12) |
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3 | (1) |
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1.2 Cell signaling systems |
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4 | (1) |
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1.3 The challenge of many moving parts |
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5 | (2) |
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1.4 The challenge of parts with parts |
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7 | (2) |
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9 | (1) |
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10 | (5) |
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2 Introduction to Statistical Methods for Complex Systems |
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15 | (24) |
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15 | (1) |
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16 | (6) |
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2.2.1 Models for dependent data |
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16 | (3) |
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19 | (3) |
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22 | (9) |
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2.3.1 Building a classifier |
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22 | (3) |
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25 | (2) |
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27 | (2) |
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2.3.4 Performance assessment |
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29 | (2) |
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31 | (5) |
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31 | (1) |
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2.4.2 (Discrete) latent variable models |
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32 | (1) |
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33 | (3) |
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36 | (3) |
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3 Bayesian Inference and Computation |
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39 | (27) |
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39 | (1) |
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3.2 The Bayesian argument |
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39 | (9) |
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39 | (2) |
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3.2.2 Bayesian analysis in action |
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41 | (1) |
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3.2.3 Prior distributions |
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42 | (4) |
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3.2.4 Confidence intervals |
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46 | (2) |
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48 | (7) |
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48 | (1) |
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48 | (1) |
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3.3.3 Point null hypotheses |
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49 | (1) |
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3.3.4 The ban on improper priors |
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50 | (2) |
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3.3.5 The case of nuisance parameters |
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52 | (2) |
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3.3.6 Bayesian multiple testing |
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54 | (1) |
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55 | (2) |
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55 | (1) |
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56 | (1) |
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56 | (1) |
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57 | (7) |
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3.5.1 Computational challenges |
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57 | (2) |
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3.5.2 Monte Carlo methods |
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59 | (2) |
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61 | (2) |
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3.5.4 Approximate Bayesian computation techniques |
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63 | (1) |
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64 | (1) |
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64 | (2) |
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4 Data Integration: Towards Understanding Biological Complexity |
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66 | (17) |
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4.1 Storing knowledge: Experimental data, knowledge databases, ontologies and annotation |
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66 | (8) |
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67 | (1) |
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4.1.2 Knowledge Databases |
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68 | (2) |
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70 | (1) |
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71 | (3) |
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4.2 Data integration in biological studies |
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74 | (3) |
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4.2.1 Integration of experimental data |
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74 | (3) |
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4.2.2 Ontologies and experimental data |
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77 | (1) |
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4.2.3 Networks and visualization software as integrative tools |
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77 | (1) |
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77 | (1) |
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78 | (5) |
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5 Control Engineering Approaches to Reverse Engineering Biomolecular Networks |
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83 | (31) |
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5.1 Dynamical models for network inference |
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83 | (6) |
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84 | (1) |
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85 | (4) |
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5.2 Reconstruction methods based on linear models |
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89 | (15) |
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89 | (1) |
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5.2.2 Methods based on least squares |
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90 | (1) |
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5.2.3 Dealing with noise: Ctls |
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91 | (6) |
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5.2.4 Convex optimization methods |
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97 | (3) |
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5.2.5 Sparsity pattern of the discrete-time model |
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100 | (1) |
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5.2.6 Application examples |
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101 | (3) |
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5.3 Reconstruction methods based on nonlinear models |
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104 | (7) |
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5.3.1 Approaches based on polynomial and rational models |
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105 | (2) |
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5.3.2 Approaches based on S-systems |
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107 | (2) |
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109 | (2) |
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111 | (3) |
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6 Algebraic Statistics and Methods in Systems Biology |
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114 | (19) |
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114 | (1) |
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115 | (1) |
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6.3 Computational algebra |
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116 | (2) |
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6.4 Algebraic statistical models |
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118 | (4) |
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118 | (1) |
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119 | (3) |
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122 | (2) |
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124 | (2) |
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126 | (3) |
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6.8 Reverse engineering of networks |
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129 | (1) |
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130 | (1) |
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130 | (3) |
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B TECHNOLOGY-BASED CHAPTERS |
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133 | (102) |
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7 Transcriptomic Technologies and Statistical Data Analysis |
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135 | (28) |
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7.1 Biological background |
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135 | (1) |
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7.2 Technologies for genome-wide profiling of transcription |
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136 | (4) |
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7.2.1 Microarray technology |
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136 | (1) |
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7.2.2 Mrna Expression Estimates From Microarrays |
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137 | (1) |
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7.2.3 High throughput sequencing (HTS) |
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137 | (2) |
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7.2.4 Mrna Expression Estimates From Hts |
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139 | (1) |
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7.3 Evaluating the significance of individual genes |
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140 | (7) |
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7.3.1 Common approaches for significance testing |
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140 | (1) |
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7.3.2 Moderated statistics |
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141 | (1) |
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142 | (1) |
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7.3.4 Multiple testing corrections |
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143 | (2) |
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145 | (2) |
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7.4 Grouping genes to find biological patterns |
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147 | (6) |
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147 | (2) |
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7.4.2 Dimensionality reduction |
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149 | (1) |
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150 | (3) |
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7.5 Prediction of a biological response |
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153 | (4) |
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153 | (3) |
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7.5.2 Estimating the performance of a model |
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156 | (1) |
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157 | (6) |
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8 Statistical Data Analysis in Metabolomics |
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163 | (18) |
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163 | (1) |
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8.2 Analytical technologies and data characteristics |
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164 | (5) |
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8.2.1 Analytical technologies |
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164 | (2) |
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166 | (3) |
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169 | (9) |
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8.3.1 Unsupervised methods |
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169 | (2) |
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171 | (1) |
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8.3.3 Metabolome-wide association studies |
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172 | (1) |
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8.3.4 Metabolic correlation networks |
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173 | (3) |
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8.3.5 Simulation of metabolic profile data |
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176 | (2) |
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178 | (1) |
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178 | (1) |
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178 | (3) |
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9 Imaging and Single-Cell Measurement Technologies |
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181 | (19) |
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181 | (1) |
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9.1.1 Intracellular signal transduction |
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181 | (1) |
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9.1.2 Lysate-based assay and single-cell assay |
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182 | (1) |
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9.1.3 Live cell and fixed cell |
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182 | (1) |
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9.2 Measurement techniques |
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182 | (12) |
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9.2.1 Western blot analysis |
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183 | (1) |
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9.2.2 Immunocytochemistry |
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183 | (1) |
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184 | (1) |
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9.2.4 Fluorescent microscope |
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185 | (2) |
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187 | (1) |
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9.2.6 Fluorescent probes for live cell imaging |
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188 | (2) |
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190 | (1) |
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191 | (3) |
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9.3 Analysis of signal cell measurement data |
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194 | (3) |
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9.3.1 Time series (mean, variation, correlation, localization |
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194 | (3) |
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9.3.2 Bayesian network modeling with single-cell data |
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197 | (1) |
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9.3.3 Quantifying sources of cell-to-cell variation |
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197 | (1) |
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197 | (2) |
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199 | (1) |
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199 | (1) |
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10 Protein Interaction Networks and Their Statistical Analysis |
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200 | (35) |
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200 | (1) |
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10.2 Proteins and their interactions |
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201 | (4) |
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10.2.1 Protein structure and function |
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201 | (1) |
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10.2.2 Protein-protein interactions |
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202 | (1) |
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10.2.3 Experimental techniques for interaction detection |
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202 | (1) |
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10.2.4 Computationally predicted data-sets |
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203 | (1) |
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10.2.5 Protein interaction databases |
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204 | (1) |
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204 | (1) |
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10.2.7 The interactome concept and protein interaction networks |
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205 | (1) |
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205 | (6) |
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205 | (1) |
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10.3.2 Network summary statistics |
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206 | (1) |
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207 | (1) |
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10.3.4 Models of random networks |
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207 | (2) |
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10.3.5 Parameter estimation for network models |
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209 | (1) |
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10.3.6 Approximate Bayesian Computation |
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209 | (1) |
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10.3.7 Threshold behaviour in graphs |
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210 | (1) |
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10.4 Comparison of protein interaction networks |
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211 | (6) |
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10.4.1 Network comparison based on subgraph counts |
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211 | (2) |
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213 | (2) |
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10.4.3 Using functional annotation for network alignment |
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215 | (2) |
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10.5 Evolution and the protein interaction network |
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217 | (1) |
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10.5.1 How evolutionary models affect network alignment |
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217 | (1) |
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10.6 Community detection in PPI networks |
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218 | (3) |
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10.6.1 Community detection methods |
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219 | (1) |
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10.6.2 Evaluation of results |
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220 | (1) |
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10.7 Predicting function using PPI networks |
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221 | (2) |
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10.8 Predicting interactions using PPI networks |
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223 | (3) |
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10.8.1 Tendency to form triangles |
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224 | (1) |
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10.8.2 Using triangles for predicting interactions |
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224 | (2) |
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10.9 Current trends and future directions |
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226 | (2) |
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226 | (1) |
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10.9.2 Integration with other networks |
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227 | (1) |
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10.9.3 Limitations of models, prediction and alignment methods |
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227 | (1) |
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10.9.4 Biases, error and weighting |
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228 | (1) |
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10.9.5 New experimental sources of PPI data |
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228 | (1) |
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228 | (7) |
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C NETWORKS AND GRAPHICAL MODELS |
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235 | (96) |
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11 Introduction to Graphical Modelling |
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237 | (18) |
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11.1 Graphical structures and random variables |
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237 | (4) |
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11.2 Learning graphical models |
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241 | (5) |
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11.2.1 Structure learning |
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242 | (4) |
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11.2.2 Parameter learning |
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246 | (1) |
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11.3 Inference on graphical models |
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246 | (1) |
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11.4 Application of graphical models in systems biology |
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247 | (4) |
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11.4.1 Correlation networks |
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247 | (1) |
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11.4.2 Covariance selection networks |
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248 | (2) |
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250 | (1) |
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11.4.4 Dynamic Bayesian networks |
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250 | (1) |
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11.4.5 Other graphical models |
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250 | (1) |
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251 | (4) |
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12 Recovering Genetic Network from Continuous Data with Dynamic Bayesian Networks |
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255 | (15) |
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255 | (1) |
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12.1.1 Regulatory networks in biology |
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255 | (1) |
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12.1.2 Objectives and challenges |
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256 | (1) |
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12.2 Reverse engineering time-homogeneous DBNs |
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256 | (5) |
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12.2.1 Genetic network modelling with DBNs |
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256 | (3) |
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12.2.2 DBN for linear interactions and inference procedures |
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259 | (2) |
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12.3 Go forward: How to recover the structure changes with time |
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261 | (6) |
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12.3.1 ARTIVA network model |
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262 | (1) |
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12.3.2 ARTIVA inference procedure and performance evaluation |
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263 | (4) |
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12.4 Discussion and Conclusion |
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267 | (1) |
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268 | (2) |
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13 Advanced Applications of Bayesian Networks in Systems Biology |
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270 | (20) |
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270 | (3) |
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270 | (2) |
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13.1.2 Dynamic Bayesian networks |
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272 | (1) |
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13.1.3 Bayesian learning of Bayesian networks |
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273 | (1) |
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13.2 Inclusion of biological prior knowledge |
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273 | (8) |
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13.2.1 The `energy' of a network |
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274 | (1) |
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13.2.2 Prior distribution over network structures |
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275 | (1) |
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13.2.3 MCMC sampling scheme |
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276 | (1) |
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13.2.4 Practical implementation |
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277 | (1) |
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13.2.5 Empirical evaluation on the Raf signalling pathway |
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277 | (4) |
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281 | (6) |
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13.3.1 Motivation: Inferring spurious feedback loops with DBNs |
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281 | (1) |
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13.3.2 A nonlinear/nonhomogeneous DBN |
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282 | (2) |
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284 | (1) |
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13.3.4 Simulation results |
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284 | (1) |
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13.3.5 Results on Arabidopsis gene expression time series |
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285 | (2) |
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287 | (1) |
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288 | (1) |
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288 | (2) |
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14 Random Graph Models and Their Application to Protein-Protein Interaction Networks |
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290 | (19) |
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14.1 Background and motivation |
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290 | (3) |
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14.2 What do we want from a PPI network? |
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293 | (1) |
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294 | (7) |
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294 | (3) |
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14.3.2 Geometric networks |
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297 | (4) |
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14.4 Range-dependent graphs |
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301 | (4) |
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305 | (1) |
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306 | (3) |
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15 Modelling Biological Networks via Tailored Random Graphs |
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309 | (22) |
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309 | (1) |
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15.2 Quantitative characterization of network topologies |
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310 | (2) |
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15.2.1 Local network features and their statistics |
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310 | (1) |
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311 | (1) |
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15.3 Network families and random graphs |
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312 | (3) |
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15.3.1 Network families, hypothesis testing and null models |
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312 | (1) |
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15.3.2 Tailored random graph ensembles |
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313 | (2) |
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15.4 Information-theoretic deliverables of tailored random graphs |
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315 | (2) |
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15.4.1 Network complexity |
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315 | (1) |
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15.4.2 Information-theoretic dissimilarity |
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316 | (1) |
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15.5 Applications to PPINs |
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317 | (6) |
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15.5.1 PPIN assortativity and wiring complexity |
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320 | (1) |
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15.5.2 Mapping PPIN data biases |
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320 | (3) |
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15.6 Numerical generation of tailored random graphs |
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323 | (2) |
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15.6.1 Generating random graphs via Markov chains |
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323 | (1) |
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15.6.2 Degree-constrained graph dynamics based on edge swaps |
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324 | (1) |
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15.6.3 Numerical examples |
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325 | (1) |
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325 | (2) |
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327 | (4) |
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331 | (86) |
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16 Nonlinear Dynamics: A Brief Introduction |
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333 | (6) |
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333 | (1) |
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16.2 Sensitivity to initial conditions and the Lyapunov exponent |
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334 | (1) |
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334 | (1) |
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16.4 The Kolmogorov-Sinai entropy |
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335 | (1) |
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336 | (2) |
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338 | (1) |
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338 | (1) |
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17 Qualitative Inference in Dynamical Systems |
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339 | (20) |
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339 | (4) |
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17.2 Basic solution types |
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343 | (3) |
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17.3 Qualitative behaviour |
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346 | (1) |
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17.4 Stability and bifurcations |
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347 | (6) |
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353 | (1) |
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354 | (2) |
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17.7 Time series analysis |
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356 | (1) |
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357 | (2) |
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18 Stochastic Dynamical Systems |
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359 | (17) |
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359 | (1) |
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18.2 Origins of stochasticity |
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359 | (1) |
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359 | (1) |
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18.2.2 Other sources of noise and heterogeneity |
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360 | (1) |
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18.3 Stochastic chemical kinetics |
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360 | (6) |
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360 | (1) |
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18.3.2 Markov jump process |
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360 | (4) |
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18.3.3 Diffusion approximation |
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364 | (1) |
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18.3.4 Reaction rate equations |
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365 | (1) |
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18.3.5 Modelling extrinsic noise |
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365 | (1) |
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18.4 Inference for Markov process models |
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366 | (6) |
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18.4.1 Likelihood-based inference |
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366 | (1) |
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18.4.2 Partial observation and data augmentation |
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367 | (1) |
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18.4.3 Data augmentation MCMC approaches |
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368 | (1) |
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18.4.4 Likelihood-free approaches |
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369 | (1) |
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18.4.5 Approximate Bayesian computation |
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370 | (1) |
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371 | (1) |
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18.4.7 Iterative filtering |
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371 | (1) |
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18.4.8 Stochastic model emulation |
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371 | (1) |
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18.4.9 Inference for stochastic differential equation models |
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372 | (1) |
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372 | (1) |
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373 | (1) |
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373 | (3) |
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19 Gaussian Process Inference for Differential Equation Models of Transcriptional Regulation |
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376 | (19) |
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376 | (3) |
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19.1.1 A simple systems biology model |
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377 | (2) |
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19.2 Generalized linear model |
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379 | (8) |
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19.2.1 Fitting basis function models |
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380 | (3) |
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383 | (2) |
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19.2.3 Gaussian processes |
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385 | (2) |
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19.2.4 Sampling approximations |
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387 | (1) |
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19.3 Model based target ranking |
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387 | (4) |
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19.4 Multiple tanscription factors |
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391 | (2) |
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393 | (1) |
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394 | (1) |
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20 Model Identification by Utilizing Likelihood-Based Methods |
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395 | (22) |
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20.1 ODE models for reaction networks |
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396 | (2) |
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397 | (1) |
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20.2 Parameter estimation |
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398 | (5) |
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20.2.1 Sensitivity equations |
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399 | (1) |
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20.2.2 Testing hypothesis |
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400 | (1) |
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20.2.3 Confidence intervals |
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401 | (2) |
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403 | (2) |
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20.3.1 Structural nonidentifiability |
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403 | (1) |
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20.3.2 Practical nonidentifiability |
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404 | (1) |
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20.3.3 Connection of identifiability and observability |
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405 | (1) |
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20.4 The profile likelihood approach |
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405 | (8) |
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20.4.1 Experimental design |
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406 | (1) |
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407 | (1) |
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20.4.3 Observability and confidence intervals of trajectories |
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407 | (1) |
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408 | (5) |
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413 | (1) |
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414 | (1) |
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415 | (2) |
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417 | (78) |
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21 Inference of Signalling Pathway Models |
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419 | (21) |
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419 | (1) |
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21.2 Overview of inference techniques |
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420 | (2) |
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21.3 Parameter inference and model selection for dynamical systems |
|
|
422 | (3) |
|
|
424 | (1) |
|
21.4 Approximate Bayesian computation |
|
|
425 | (1) |
|
21.5 Application: Akt signalling pathway |
|
|
426 | (9) |
|
21.5.1 Exploring different distance functions |
|
|
428 | (2) |
|
|
430 | (1) |
|
21.5.3 Parameter sensitivity through marginal posterior distributions |
|
|
430 | (1) |
|
21.5.4 Sensitivity analysis by principal component analysis (PCA) |
|
|
430 | (5) |
|
|
435 | (1) |
|
|
436 | (4) |
|
22 Modelling Transcription Factor Activity |
|
|
440 | (11) |
|
|
|
|
|
22.1 Integrating an ODE with a differential operator |
|
|
441 | (2) |
|
22.2 Computation of the entries of the differential operator |
|
|
443 | (4) |
|
22.2.1 Taking into account the nature of the biological system being modelled |
|
|
443 | (2) |
|
22.2.2 Bounds choice for polynomial interpolation |
|
|
445 | (2) |
|
|
447 | (2) |
|
22.4 Estimating intermediate points |
|
|
449 | (1) |
|
|
450 | (1) |
|
|
450 | (1) |
|
23 Host-Pathogen Systems Biology |
|
|
451 | (16) |
|
|
|
451 | (2) |
|
|
453 | (1) |
|
|
453 | (2) |
|
23.4 Protein-protein interactions |
|
|
455 | (2) |
|
23.5 Response to environment |
|
|
457 | (1) |
|
23.6 Immune system interactions |
|
|
458 | (1) |
|
23.7 Manipulation of other host systems |
|
|
459 | (1) |
|
23.8 Evolution of the host-pathogen system |
|
|
460 | (2) |
|
23.9 Towards systems medicine for infectious diseases |
|
|
462 | (1) |
|
|
462 | (1) |
|
|
463 | (1) |
|
|
463 | (4) |
|
24 Bayesian Approaches for Mass Spectrometry-Based Metabolomics |
|
|
467 | (10) |
|
|
|
|
|
|
467 | (1) |
|
24.2 The challenge of metabolite identification |
|
|
468 | (1) |
|
24.3 Bayesian analysis of metabolite mass spectra |
|
|
469 | (2) |
|
24.4 Incorporating additional information |
|
|
471 | (1) |
|
24.5 Probabilistic peak detection |
|
|
472 | (1) |
|
24.6 Statistical inference |
|
|
473 | (1) |
|
24.7 Software development for metabolomics |
|
|
474 | (1) |
|
|
475 | (1) |
|
|
475 | (2) |
|
25 Systems Biology of microRNAs |
|
|
477 | (18) |
|
|
|
|
477 | (1) |
|
25.2 Current approaches in microRNA Systems Biology |
|
|
477 | (1) |
|
25.3 Experimental findings and data that guide the developments of computational tools |
|
|
478 | (1) |
|
25.4 Approaches to microRNA target predictions |
|
|
479 | (3) |
|
25.5 Analysis of mRNA and microRNA expression data |
|
|
482 | (3) |
|
25.5.1 Identifying microRNA activity from mRNA expression |
|
|
482 | (2) |
|
25.5.2 Modeling combinatorial microRNA regulation from joint microRNA and mRNA expression data |
|
|
484 | (1) |
|
25.6 Network approach for studying microRNA-mediated regulation |
|
|
485 | (1) |
|
25.7 Kinetic modeling of microRNA regulation |
|
|
486 | (4) |
|
25.7.1 A basic model of microRNA-mediated regulation |
|
|
487 | (1) |
|
25.7.2 Estimating fold-changes of mRNA and proteins in microRNA transfection experiments |
|
|
488 | (1) |
|
25.7.3 The influence of protein and mRNA stability on microRNA function |
|
|
489 | (1) |
|
25.7.4 Microrna Efficacy Depends On Target Abundance |
|
|
489 | (1) |
|
25.7.5 Reconstructing microRNA kinetics |
|
|
489 | (1) |
|
|
490 | (1) |
|
|
491 | (4) |
Index |
|
495 | |