Microarray Bioinformatics

Half-title......Page 3
Title......Page 5
Copyright......Page 6
Dedication......Page 7
Contents......Page 9
Foreword......Page 11
Preface......Page 13
Outline of Contents......Page 14
Acknowledgments......Page 15
MICROARRAY BIOINFORMATICS......Page 17
SECTION 1.2 MAKING MICROARRAYS......Page 19
Spotted Microarrays......Page 21
In-Situ Synthesised Oligonucleotide Arrays......Page 23
Maskless Photodeprotection Technology......Page 24
Synthesis Yields......Page 25
SECTION 1.3 USING MICROARRAYS......Page 27
Sample Preparation and Labelling......Page 28
Hybridisation......Page 29
Washing......Page 31
Image Acquisition......Page 32
KEY POINTS SUMMARY......Page 34
SCANNERS......Page 36
SECTION 2.1 INTRODUCTION......Page 37
SECTION 2.2 PRIMARY SEQUENCE DATABASES......Page 41
SECTION 2.3 SECONDARY SEQUENCE DATABASES......Page 45
UniGene......Page 46
The TIGR Gene Indices......Page 51
RefSeq......Page 52
Ensembl......Page 55
Microbial Genomes......Page 56
Yeast......Page 58
INTERNET RESOURCES......Page 59
RESEARCH PAPERS......Page 60
What Makes a Good Oligonucleotide Probe?......Page 61
RepeatMasker......Page 63
SECTION 3.3 PREDICTION OF CROSS-HYBRIDISATION TO RELATED GENES......Page 65
SECTION 3.4 THE THERMODYNAMICS OF NUCLEIC ACID DUPLEXES AND THE PREDICTION OF MELTING TEMPERATURE......Page 70
Base-Stacking and Initiation Parameters......Page 71
Adjustments for Salt Concentrations......Page 73
SECTION 3.5 PROBE SECONDARY STRUCTURE......Page 74
Computation of Probe Secondary Structure......Page 75
Using Mfold over the Web......Page 76
KEY POINTS SUMMARY......Page 77
Software Available for Download from the Internet......Page 78
SECTION 4.2 FEATURE EXTRACTION......Page 80
Identifying the Positions of the Features......Page 82
Fixed Circle Segmentation......Page 84
Histogram Segmentation......Page 85
Identifying the Background Pixels......Page 86
Calculation of Numerical Information......Page 87
Books......Page 90
Removing Flagged Features......Page 91
Affymetrix Data......Page 92
Taking Logarithms......Page 93
SECTION 5.3 WITHIN-ARRAY NORMALISATION......Page 98
Linear Regression of Log Ratio Against Average Intensity......Page 99
Nonlinear Regression of Log Ratio Against Average Intensity......Page 102
Two-Dimensional Loess Regression......Page 105
Block-by-Block Loess Regression......Page 107
SECTION 5.4 BETWEEN-ARRAY NORMALISATION......Page 108
Visualising the Data: Box Plots......Page 111
Distribution Normalisation......Page 114
Data Set 5B......Page 115
Useful Normalisation Resources......Page 116
Calibration Experiments......Page 118
Pilot Studies......Page 119
Log-Normal Distribution......Page 120
Method for Measuring Variability......Page 121
Variation Between Replicate Features on an Array......Page 122
Variability Between Hybridisations to Different Arrays......Page 124
KEY POINTS SUMMARY......Page 126
Data Set 6B......Page 127
SECTION 7.1 INTRODUCTION......Page 128
Statistical Inference......Page 130
Hypothesis Tests and P-values......Page 131
Independence......Page 132
Paired or One-Sample t-Test......Page 133
Unpaired or Two-Sample t-Test......Page 135
Requirements of t-Tests......Page 137
SECTION 7.4 NON-PARAMETRIC STATISTICS......Page 141
Classical Non-parametric Statistics......Page 142
Bootstrap Analyses......Page 145
SECTION 7.5 MULTIPLICITY OF TESTING......Page 156
Estimation of False Positive Rate......Page 157
Bonferroni Adjustment......Page 159
The One-Way ANOVA......Page 160
Multifactor ANOVAs......Page 161
Data Set 7A......Page 162
Publications for Microarray Analysis Methods......Page 163
Internet Resources......Page 164
SECTION 8.1 INTRODUCTION......Page 165
SECTION 8.2 SIMILARITY OF GENE OR SAMPLE PROFILES......Page 166
Features of a Distance Measure......Page 167
Correlation Coefficient......Page 168
Spearman Correlation......Page 171
Euclidean Distance......Page 174
SECTION 8.3 DIMENSIONALITY REDUCTION......Page 177
Principal Component Analysis......Page 178
How PCA Works......Page 179
Multidimensional Scaling......Page 181
SECTION 8.4 HIERARCHICAL CLUSTERING......Page 184
Linkage Methods......Page 189
Isomorphisms......Page 193
SECTION 8.5 THE RELIABILITY AND ROBUSTNESS OF HIERARCHICAL CLUSTERING......Page 194
Parametric Bootstrapping......Page 195
Construction of a Consensus Tree......Page 197
The K-Means Algorithm......Page 200
How to choose a good value of k?......Page 201
Validating K-Means Clustering......Page 202
Choosing the Size of a Self-Organised Map......Page 203
Validation of Self-Organised Maps......Page 205
KEY POINTS SUMMARY......Page 206
Internet Resources......Page 207
SECTION 9.1 INTRODUCTION......Page 209
Separability......Page 210
Number of Classes......Page 213
K-Nearest Neighbours......Page 215
Linear Discriminant Analysis......Page 217
Support Vector Machines......Page 219
Training and Test Sets......Page 221
Cross-Validation......Page 223
SECTION 9.4 DIMENSIONALITY REDUCTION......Page 224
Principal Component Analysis......Page 226
Individual Gene Selection......Page 228
Pairwise Gene Selection......Page 230
Voting Algorithms......Page 231
Genetic Algorithms......Page 232
The Algorithm......Page 233
KEY POINTS SUMMARY......Page 234
Data Set 9B......Page 235
Books......Page 236
SECTION 10.2 BLOCKING, RANDOMISATION AND BLINDING......Page 237
Bias, Randomisation and Blinding......Page 239
SECTION 10.3 CHOICE OF TECHNOLOGY AND ARRANGEMENT OF SAMPLES......Page 240
Estimating Variability......Page 242
Confounding and Colour Swaps......Page 243
SECTION 10.4 HOW MANY REPLICATES?......Page 247
Confidence and Power......Page 248
Types of Replicates......Page 249
Standard Deviation......Page 250
Power Analysis Calculation and Tables......Page 251
Papers from Which We Have Used Data or Experimental Design Ideas......Page 255
SECTION 11.1 INTRODUCTION......Page 257
Local Data Warehousing......Page 259
Data Analysis and Visualisation......Page 261
The Need for Standards......Page 263
The Microarray Gene Expression Data Society (MGED)......Page 264
Array Design Description......Page 265
Experiment Description......Page 267
SECTION 11.4 ONTOLOGIES......Page 270
Gene Ontologies and the GO Consortium......Page 271
Properties......Page 275
Individuals......Page 276
Public Microarray Databases......Page 277
Useful Papers......Page 278
APPENDIX MIAME Glossary......Page 279
INDEX......Page 285