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Contents

Preface

v

List of Contributors

xi

1 The ALL Dataset
F. Hahne and R. Gentleman
1.1
Introduction . . . . . . . . . .
1.2
The ALL data . . . . . . . . .
1.3
Data subsetting . . . . . . . . .
1.4
Nonspecific filtering . . . . . .
1.5
BCR/ABL ALL1/AF4 subset

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2 R and Bioconductor Introduction
R. Gentleman, F. Hahne, S. Falcon,
and M. Morgan
2.1
Finding help in R . . . . . . . . . .
2.2
Working with packages . . . . . .
2.3
Some basic R . . . . . . . . . . . .
2.4
Structures for genomic data . . . .
2.5
Graphics . . . . . . . . . . . . . . .
3 Processing Affymetrix Expression
R. Gentleman and W. Huber
3.1
The input data: CEL files . . . .
3.2
Quality assessment . . . . . . . .
3.3
Preprocessing . . . . . . . . . . .
3.4
Ranking and filtering probe sets
3.5
Advanced preprocessing . . . . .
4 Two-Color Arrays
Florian Hahne and Wolfgang
4.1
Introduction . . . . .
4.2
Data import . . . . .
4.3
Image plots . . . . . .

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Huber
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.7 The interpretation of glog-ratios . . . . . . . . . . . 74 78 79 81 83 . . . .1 Motivation . . . . .2 Nonspecific filtering . . . . Hahne 8. . . 6. . . . . . . . . . . . . . . . . .3 Categories and overrepresentation . . . . . . . . . . . . . .1 Our data . . . . . . . . . . . . . . . . . . Scholtens. . . . . .3 Differential expression . . . . . . . . . . . . . . . . . . . . . . . . . Hahne. 7. 8. . . . . . . . Differential expression . . .5 Other annotations available . 5. . . . . . . . . . . . . . . . . . . . . 83 84 85 87 89 . . . . 7. . . . . .4 Working with GO . . . F. . .8 Reference normalization . 8. 7. . . . .3 Differential expression . . . 89 90 92 94 95 . 7. . 7. 63 65 70 72 . . . . . . . . . . . . . . . and Variance Stabilization W. . . . . . . . . . . . .3 Calling VSN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. .1 Example data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. . . .7 When power increases . . . . . . . . . 5 Fold-Changes. . . von Heydebreck 7. . . . . . . .2 Nonspecific filtering . . . Huber 6. . . . . . . . . .2 Background-correction and generalized logarithm . . 6. . . 5. . . . . . 5. . . . . 103 106 107 109 112 113 115 . .6 biomaRt . . . . . . . . . 6 Easy Differential Expression F. . . . 99 101 103 . . 7 Differential Expression W. . . . . . . . . . . . . . . . . Log-Ratios. . . . D. . . . . . . . . . . . . . Shrinkage Estimation. . . . . . 5. . . . 8 Annotation and Metadata W. . . . .4 Multiple testing . . .5 Normalization . . .6 Single-color normalization . Background Correction. . . . . . . . . . . . . . . . . . . . . . .5 Robust fitting and the “most genes not differentially expressed” assumption . . .4 4. . . . . . . . 8. . Hahne and W. .6 Gene selection by Receiver Operator Characteristic (ROC) . 7. . . . . . . . . . .1 Fold-changes and (log-)ratios . . . . . . . Huber and F. . . . . . . . . . . . . . 8. . . . . . . . . . . . . . . . .5 Moderated test statistics and the limma package . . . . . . . . . . . . . . . . . . . . 8. . . . . . .4 How does VSN work? . . . . . . . . . . . . . 5. . . . . . . .viii Contents 4. . . . . . . . . . . . . and A. .2 Multiple probe sets per gene . . . . . . . . . . . . . . . .7 Database versions of annotation packages . . . . . . 8. . . . . . . . . . . 6. . . . . Huber 5. . . . . . Huber. . . . . . . . .4 Multiple testing correction 50 57 63 . . . . .

. . . . . . . . . . . .4 Selecting a distance . . . 10.8 Multigroup classification . . . . 10. . 11. . . . .4 Subgraphs . . . . . . . . . . . . . . Gentleman 12. . . . . . . . . . . . . . . . . . . . .5 Tooltips and hyperlinks on graphs . . Carey 9. . 10. . . . . . . . 11 Using Graphs for Interactome Data T. J. . . . . . . . . . . . . . . . .3 How many clusters? . . . . . .Contents 9 Supervised Machine Learning R. . . . . . . . 137 139 142 144 146 148 151 152 154 157 159 . . . . . . Chiang. . . . . . . . . . . . . . . . . . . . . . . . . . and W. and V. . . . . . . . . . . .1 Preliminaries . . .2 Layout and rendering using Rgraphviz 12. . . . . . . . . . . 12 Graph Layout F. . . . . . . . . . 10. . . . . . .2 The example dataset . . . . . . . . . . . . . . . . . . . Huber. . . . . . . .3 Directed graphs . . . . 12. . . 11. . . . . . . . . . . . Hahne. . . . . . . . . . . 10. . . . . . . . . . . J. . . .5 Partitioning methods . . . . 9. . F. . . . . . . . . . . . . .6 Self-organizing maps . Carey 10. . . . . Gentleman. . . . . . . . . . 9. . . . . . . . 12. . . . Gentleman and V. . . .1 Introduction . . . . . . . . . . . . . . . . . . . . . . . .10 Remarks . . . . . . . . . . . . . . . .6 Reading PSI-25 XML files from IntAct with the Rintact package . . . . . . . . . Huber 11. . . . . . . . . . Falcon. . .5 Some harder problems . . . . .1 Introduction . . . . . . . . . . . 164 165 . . . . . . . . . . . .4 Hierarchical clustering . . ix 121 . .7 Hopach . . . . . . . . .3 The co-expression graph .5 Machine learning . . . . . . . .4 Testing the association between physical interaction and coexpression . . . . 10. . . 10. . . . . . 9. and R. . . . . .2 Exploring the protein interaction graph . . .2 Distances . . . . . . . . . . . . . W. . . . . . . . . . . . . . . . . . . . . 9. . . . . . .8 Silhouette plots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10. . . . . . . .3 Feature selection and standardization 9. . . . . . 159 160 162 . . . . . . . . . . . . W. . . 11. . . . 121 123 124 124 126 129 132 135 137 . . . . . . . . . . 173 175 180 185 187 . . . . . . . . . . . . . . . . . . . . . . . . . . .9 Exploring transformations . . . . . . . .1 Introduction . . . . . . . . . . . . 11. . . . . . . . . . . . . 165 173 . . . . 11. . . . . . . . . . . . . . . 10 Unsupervised Machine Learning R. . 10. . . . . . . . . . . . . . . . . . . . . . 12. Huber. . . . . . . .7 Random forests . S. . . . . . . .6 Cross-validation . . . . Hahne. . 9. . . . . . 9. . .

. . . . . . . . . . . . . . . . . . . . . . 14. . . . . . . . . . . . . . . 207 208 209 215 218 219 . . . . . . 3 Processing Affymetrix Expression Data . . . . 5 Fold-Changes. . . . . . . . . . . . . . . . 221 221 226 230 . . . . . . . . .2 Data analysis . . . . . . . . . 193 13. .1 Introduction . . . . . . . 6 Easy Differential Expression . Gentleman 14. . . .2 The basic problem . . . . . . . . . . . . . Shrinkage Estimation. . . . . . . . . . . . . . . . . . . . . . . . . . M. . . . Set Enrichment 207 . . . . . 8 Annotation and Metadata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 14 Hypergeometric Testing Used for Gene Analysis S. . . . . . . . . . 9 Supervised Machine Learning . . . . . .1 Introduction . . . 15 Solutions to Exercises 2 R and Bioconductor Introduction . . . . . . . . . . . . 13 Gene Set Enrichment Analysis . . . . . . 4 Two-Color Arrays . . Huber 13. 14 Hypergeometric Testing Used for Gene Set Enrichment Analysis . . . Background Correction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14. . . . . . . . . . . . . . . . .3 Preprocessing and inputs . . . . . . . . . . . . . 231 233 233 234 241 249 256 259 261 . . . Gentleman.5 The conditional hypergeometric test . . 7 Differential Expression .6 Other collections of gene sets . . . . . . . . . . . . . . . . . . . . . . . .4 Outputs and result summarization . . . .x Contents 13 Gene Set Enrichment Analysis 193 R. . . . . 14. . 265 References 271 Index 277 . . . . . . . . . . . . . . . and Variance Stabilization . 12 Graph Layout . . . . . . . . . 11 Using Graphs for Interactome Data . . . . . . . . . . 196 13. . Log-Ratios. . . . . . Morgan. . . . . . . . . . . . . . 14. . . . . . . 10 Unsupervised Machine Learning . Falcon and R.3 Identifying and assessing the effects of overlapping gene sets . . . . . . . . . . . . . and W. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14. . . . . . . .

springer.http://www.com/978-0-387-77239-4 .