Index

A-dependent, 96a posteriori probability, 18accessor methods, 87adaptive gene discovery, 55Affymetrix, 102, 231Affymetrix arrays, 381Affymetrix GeneChipTM, 166Affymetrix Microarray Analysis

Software, 442agglomerative clustering, 23, 171algorithms, hierarchical clustering,

186alongChrom, 59amplicon, 59analysis

agglomerative cluster, 171bootstrap, 338χ2, 198cluster, 243, 328, 334dendrogram, 243discriminant, 33exploratory, 73exploratory data, 12, 111extendable, 246factor, 395genetic network, 186hierarchical cluster, 179, 338image, 7K-means, 336k-means cluster, 334linear discriminant, 138model-based expression, 120principal components, 26, 186probe-level, 6, 120promoter, 155sensitivity, 23toxicity, 186unsupervised, 383

analysis of variance (ANOVA), 254,315, 317, 322, 332, 336

annotate, 47annotation, 57, 185

biological, 188ANOVA model, 296anticancer agents, 438ArrayExpress, 159array layout, 76array outliers, 130, 131array surface, 224arrays

cDNA, 3oligonucleotide, 3, 120

artifacts, 223assignment methods, 88atomic prior, 395autoregressive, 411Autoregressive Score, 420average linkage, 148

background, 3,noise, 5

background fluorescence intensity,76

background subtraction, 13, 214,322

balanced, 323BASE, 36Bayesian approach, 363Bayesian hierarchical model, 17,

367, 385Bayesian model-based, 411Bayesian networks, 432biases, dye, 4, 73binning, 435biobase, 46Bioconductor, 11, 73

447

448 Index

biological annotation, 188biological regulatory pathways, 429biological variation, 5, 318Bioperl Project, 10block structure, incomplete, 9Bonferroni corrections, 169Boolean network, 435bootstrap, 338bootstrapping, 324, 326boxplots, 73BRB, 35

χ2 analysis, 198calibration, 30cancer, 388cancer applications, 366cColor, 63CDF file, 105, 126cDNA arrays, 3CEL files, 104, 126cell cycle, 388cellular pathways, 197channels, 3chromosomes, matching genes to,

137class, object-oriented, 73class prediction, 29classesexprSet, 51phenoData, 51

classification, 7, 363model-based, 57molecular, 363nearest-neighbor, 56sample, 138text-based, 57

classification rate, correct, 31classification trees, 32classifiers, nearest-neighbor, 33clinical laboratory results, 432closure, 55cluster, 21, 22cluster analysis, 243, 328, 334cluster distance, 235clustergram, 235, 243clustering, 7, 259, 327, 362

K-means, 235k-means, 25K-median, 235

agglomerative, 23divisive, 23fuzzy, 171hierarchical, 21, 120, 133, 148,

171, 173, 235, 328, 334hierarchical algorithms, 186

clustering methods, 235clusters, 430

number of, 410CODA, 372coefficient of variation, 265, 266coercing methods, 88color palette, 92color schemas, heat-map, 150combine comparisons, 136comparing samples, 135complete linkage, 148confidence intervals, 122, 324, 326,

333consensus tree, 328, 338control, 73conversion, data, 238correct classification rate, 31correction, local variance, 219corrections

Bonferroni, 169Fisher’s LSD, 169

correlation, 410correlation coefficients, 430cPlot, 63CRAN, 12cross-validation, 31current gene, 234current sample, 232Cvt2Mae data converter “wizard,”

231Cyber-T, 18, 35

datamissing, 287, 339normalized, 317probe–level, 103survival, 285

data augmentation, 368data conversion, 238data filtering, 144data input, 73data visualization, 189data-mining strategy, 385

Index 449

databases, 10dChip, 15, 120dendrogram, 22, 235, 243, 430density

posterior, 412prior, 412

density function, Parzan, 437design, 335

experimental, 9, 316, 317loop, 319reference, 9, 319, 324unbalanced, 319

diabetes, 292, 306diagnostic plots, 73diagnostics, 332differential gene expression, 258,

263, 273multiple conditions, 258two conditions, 263

dimension reduction, 385discrete probabilities, 435discretization, 151

histogram-based, 151discriminant analysis, 33dissimilarity measure, 431, 443distance

cluster, 235Euclidean, 430matrix, 23

distance matrix, 23distribution

hierarchical, 367joint, 437uniform, 366

divisive clustering, 23DNA, 1downloading software, 247DRAGON, 185drug screening, 186dye biases, 4, 73dye-swap, 318, 324dyes, 3

EBarray, 18edd, 47, 56, 68edge effects, 5edges, 431Edited Gene List (EGL), 233, 241,

242

element signal intensity, 217empirical Bayes (EB), 17, 254

advantages, 256methods, 256

Encapsulated PostScript (EPS),444

entropy, 434EP:GO, 152EP:PPI, 153EPCLUST, 143estimates

local pooled error (LPE), 166shrinkage variance, 299

Euclidean distance, 410, 430examplesedd, 68

experimental design, 9, 316, 317exploratory data analysis, 12, 73,

111expression

gene, 185mRNA, 185

expression density diagnostics, 55expression indexes, 120expression measures, 113expression profile plots, 242Expression Profiler (EP), 142exprSet, 51extendable analysis, 246

F statistic, 325, 327F -test, 327, 332, 333, 336factor, transcription, 437factor analysis, 395false discovery rate, 18, 274, 327familywise error rate, 327FDR, 274files

CDF, 126CEL, 126gene information, 126

filtering, 385data, 144gene, 7, 64, 132joint, 54marginal, 54

Fisher’s LSD corrections, 169fixed effects, 270fold changes, 122, 164, 257

450 Index

foreground, 76function

likelihood, 413loess, 217Parzan density, 437probability density, 435Sweave, 75

functionally significant cluster, 134functions, gene-mining, 377fuzzy clustering, 171

Gamma-Gamma model, 259Gap statistic, 345Gap tolerance, 346GenBank, 192gene, 1

current, 234filtering, 7working set of, 232

GeneChip, 3, 102GeneCluster, 34gene discovery, adaptive, 55gene expression, 1, 185

differential, 273microarrays, 2serial analysis of, 189

gene expression dynamics, 411gene filter, 50genefilter, 47gene filtering, 64gene information files, 126gene-mining, 377gene ontology, 58, 152GenePix, 89, 231geneplotter, 47gene shaving, 342GeneSOM, 25GeneX, 35genetic network analysis, 186genome biometry, 6genome-wide expression patterns,

58GENOMES, 156global normalization, 214GMEP, 34GMF, 444goodness-of-fit score, 417graph, 431grid, 76

hash tables, 57heat-map color schemas, 150hierarchical Bayesian, 17hierarchical clustering, 21, 120,

133, 148, 171, 173, 179, 186,235, 328, 334, 338

hierarchical distributions, 367hierarchical model, Gamma-

Gamma, 259high-density oligonucleotide

expression array, 102histogram, 435histogram-based discretization, 151homologene, 35housekeeping genes, 299HTML, 225hybridization, 2, 3hypothesis-testing, 323

identifiersSGD, 152

image analysis, 7image contamination, 128image files, 76image-processing, 77imaging, 5incomplete block structure, 9index

model-based expression, 122probe-sensitivity, 122

informationmutual, 434–436threshold mutual, 436

information-abundant visualizationmethods, 196

information measure, 347intensity

background fluorescence, 76element signal, 217

intensity-dependent, 96interactions, protein–protein, 153invariant set, 121invariant set normalization, 129iterative data-mining process, 237

Java, 229, 244, 440, 441java.graph, 164Java Virtual Machine (JVM), 245joint, 54

Index 451

joint distribution, 437joint filtering, 54journal watch, 5

K-means clustering, 25, 148, 171,186, 196, 235, 243

analysis, 334, 336K-median clustering, 235knnTree, 33Kyoto Encyclopedia of Genes and

Genomes (KEGG), 185

L-plastin, 438laboratory tests, 433language

object-oriented, 12pattern, 156R statistical, 225S, 11

large-scale visualization methods,196

latent categories, 365latent qualitative variables, 385lda, 33least squares, 322, 332Li-Wong model, 15library

OOML, 36rpart, 32tree, 32

likelihood, 392likelihood function, 413linear discriminant analysis (LDA),

138linkage

average, 148complete, 148single, 148

linlog, 322, 331local mean normalization, 217local normalization, 212local pooled error (LPE) estimates,

166local variance correction, 219location normalization, 73, 79loess, 79, 217log ratio, 77log transform, 321, 322logarithm, 435

logarithmic scale, 321Lognormal-Normal model, 260logos

sequence, 157loop, 324loop design, 319lowess, 79, 321, 322, 331LPE method, 18LPE test, 170lung cancer, 381

MA plot, 13, 79machines, support vector, 33MADAM, 34mAdb, 231MAEPlugins, 230, 244MAExplorer, tutorial on using, 249MAGE, 10, 159MAGE-ML, 10, 144MAGE-OM, 10mapping genes to chromosomes,

137maps, self-organizing, 25, 186marginal, 54marginal filtering, 54marginal likelihood, 413marginal profiles, 370Markov chain Monte Carlo

(MCMC), 363, 391marrayClasses, 73marrayInput, 73marrayPlots, 73MatArray, 36match, perfect, 3matching, template, 35matrices, position weight, 154matrix

decomposition, 390distance, 23similarity, 23

mclust, 22MCMC, 372mda, 33measure, dissimilarity, 431, 443median, 96median absolute deviation, 80medoids, partitioning around, 171metadat, 50method, object-oriented, 73

452 Index

methods, 51, 73accessor, 87adaptive gene discovery, 55assignment, 88clustering, 235coercing, 88empirical Bayes, 254, 256global normalization, 214hierarchical clustering, 173information-abundant

visualization, 196large-scale visualization, 196partitioning, 173printing, 85subsetting, 87supervised, 21, 428unsupervised, 21, 428visualization, 215

metrics, 23Metropolis–Hastings MCMC,

367MeV, 21, 35MGAP, 230MGED, 10MIAME, 10MicroArray Explorer, 229microarray surface, 223microarrays, 73, 185

gene expression, 2MIDAS, 35mining, 362, 363, 385MIPS, 156mismatch (MM ), 4missing data, 287, 339, 429mixed model, 317, 339mixing over, 258mixture model, 26, 258, 364, 366,

368, 376model

Bayesian, 391Bayesian hierarchical, 367, 385Gamma-Gamma, 259Li-Wong, 15Lognormal-Normal, 260mixture, 26, 258, 364, 366, 368,

376model-based classification, 57model-based expression analysis,

120

model-based expression index, 122,131

molecular class discovery, 362molecular classification, 363molecular profiles, 362, 370, 379,

385molecular subclasses, 362mRNA, 1mRNA expression, 185multiclass response, 284multidimensional scaling, 27multimodality, 55multiple conditions, 258multiple hypothesis testing, 272multiple-comparison, 300multiple-testing, 326mutual information, 434–436MySQL, 10, 192

National Cancer Institute, 437NC160, 437, 438NCI60 dataset, 29nearest-neighbor classification, 56nearest-neighbor classifiers, 33negative associations, 428negative interactions, 430network, 429, 434, 438

Bayesian, 432Boolean, 435relevance, 21, 429

noise, background, 5nonparametric, 277normal distribution, 365normal scores, 296normal-scores transformation,

294normalization, 6, 73, 108, 121, 240,

293, 296, 323alternative method, 293global, 214invariant set, 129local, 212local mean, 217location, 73, 79quantile, 15scale, 73, 80

normalize, 292normalized data, 317number of clusters, 410

Index 453

object-oriented, 73language, 12programming, 51

oligonucleotide array, 3, 120ontologies, 11OOML, 36open-source, 73, 247outlier-proneness, 55outliers

array, 130, 131probe, 130single, 130, 131

p53, 430p-values, 18, 324, 326packagesannotate, 47Biobase, 46edd, 47, 56genefilter, 47geneplotter, 47marrayClasses, 73marrayInput, 73marrayNorm, 73methods, 51R, 73sma, 74

palette representation, 151partitioning, 173partitioning around medoids, 171Parzan density function, 437Pathlinx, 440pathophysiology, 433pathways, 429PATMATCH, 154pattern

discovery, 154genome-wide expression, 58language, 156matching, 154

perfect match (PM ), 3Perl, 192, 225permutation sampling, 169permutations, 324, 439, 443Pfam, 185, 189pharmaceuticals, 437pharmacogenomic, 437phenoData, 51phenotypic, 430

physiology, 433Pickgene, 18pin-group, 76pixels, 3plates, 76plots

diagnostic, 73expression profile, 242silhouette, 173whole genome, 62

POE, 371, 374poe.bigpicture, 374poe.fit, 372poe.mine, 377poe.onegene, 376poe.profile, 379pooling replicate arrays, 124Portable Document Format (PDF),

444position weight matrices, 154posterior density, 392, 412posterior probability, 255, 411postgresql, 10preprocessing, 74principal components analysis, 26,

186, 343print tip, 4print-tip-group, 76printing methods, 85prior, 392

atomic, 395prior density, 412probabilities, discrete, 435probability, a posteriori, 18probability density function

(PDF), 435probability scale, 385probe outliers, 130probe-level analysis, 6, 120probe-level data, 103probe-sensitivity index, 122probes, 3, 76process, iterative data-mining,

237profiles

marginal, 370molecular, 362, 370, 385

programming, object-oriented, 51promoter analysis, 155

454 Index

protein, 1protein–protein interactions, 153

qda, 33quality control, 12quantile normalization, 15quantizing, 435

R statistical language, 11, 73, 225,371

software 139, 363randomization, 324rates, false discovery, 18, 327ratio, signal-to-noise, 18reference design, 9, 319, 324reference sample, 319, 324refinement, 30relational database management

system, 191relative expression values, 316, 317,

327, 336relevance networks, 21, 429RelNet, 440, 441replicate sample, 232replication, 7reports, 243residuals, 323RI plot, 321riplot, 331robust adaptive location, 73robust locally-weighted regression,

79robust multichip average (RMA),

114rpart, 32

S language, 11S-PLUS Graphlet, 180SAM, 18sample

classification, 138current, 232reference, 319, 324replicate, 232size, 7

sampling, permutation, 169saturation, 5scale normalization, 73, 80scaling, multidimensional, 27

Scanalyze, 231scatterplots, 73, 235, 242searches

similarity, 149similarity-based, 153

sector, 76segmentation, 12selection, 7self-organizing maps, 25, 186sensitivity analysis, 23SEQLOGO, 154sequence logos, 157serial analysis of gene expression

(SAGE), 189SGD, 152shift-log, 322shrinkage estimates, 255, 257shrinkage variance estimates, 299signal-to-noise ratio, 18signaling, 388signaling pathways, 389signed mean gene, 344significant genes, 288silhouette plots, 173similarity-based search, 153similarity matrix, 23similarity searches, 149simulated annealing, 396single linkage, 148single outliers, 130, 131singular value decomposition, 343skewness, 55sma, 74smoothing, 79smoothing splines, 298software, 225

downloading, 247R, 139, 363

SOTA, 149sources of variation, 4spatial, 96, 223spatial color images, 73SPEXS, 154spot, 3, 89Spotfinder, 35standard errors, 120Stanford Saccharomyces Genome

Database (SGD), 152stationary time series, 412

Index 455

StatServer r©, 180strategy

agglomerative, 415data-mining, 385

structure, metadata, 50Student’s t-tests, 254subclasses, molecular, 362subsetting methods, 87substrate, 429subtraction, background, 13supercluster, 149supervised methods, 21, 428supervised shaving, 346support vector machines, 33surface, array, 224survival data, 285Sweave, 75SwissProt, 152, 185, 189systems biology, 429

t-test, 186, 325targets, 75tcltk, 74technical variation, 318template matching, 35text-based classification, 57text files, 441threshold, 432threshold mutual information

(TMI), 436time series, 410TM4, 34tools

molecular profiling, 379visualization, 374

toxicity analysis, 186transcription, 1transcription factor, 437transformation, 331

normal-scores, 294variance-stabilizing, 322

translation, 1trees, 32

classification, 32TreeView, 21, 178, 196tumor suppressor gene, 430

tutorial, using MAExplorer, 249tutorials, 75two class, 284two conditions, 256two-sample t-statistics, 169

unbalanced design, 319uniform distribution, 366UniGene, 185, 189unsupervised methods, 21, 362,

383, 428URLMAP, 151

validation, 30values, relative expression, 316,

317, 327, 336variables, latent qualitative, 385variance-stabilizing transformation,

322variation

biological, 5, 318sources of, 4technical, 318

visualization, 21, 58, 185, 196, 331,362, 363, 369, 385

alongChrom, 59cColor, 63cPlot, 63data, 189

visualization methods, 215information-abundant, 196large-scale, 196

visualization tools, 374volcano plot, 333, 336

watch, journal, 5Web implementation, 225whole genome plots, 62widgets, 73working set of genes, 232World Wide Web (WWW), 188

XML, 57, 144Xpogen, 440

Z-scores, 222