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Introduction to bioinformatics / Arthur M. Lesk.

By: Material type: TextTextPublication details: Oxford ; New York : Oxford University Press, 2005.Edition: 2nd edDescription: xviii, 360 p., 10 p. of plates : ill. (some col.) ; 25 cmISBN:
  • 9780199277872
Other title:
  • Bioinformatics
Subject(s): DDC classification:
  • 570.285 21
Contents:
1 Introduction 1 Life in space and time 3 Evolution is the change over time in the world of living things 4 Dogmas: central and peripheral 6 Observables and data archives. 9 Information flow in bioinformatics 12 Curation, annotation, and quality control 13 The World Wide Web 14 Electronic publication 15 Computers and computer science 16 Programming 17 Biological classification and nomenclature 21 Use of sequences to determine phylogenetic relationships 24 Use of SINES and LINES to derive phylogenetic relationships 30 Searching for similar sequences in databases: PSI-BLAST 32 Introduction to protein structure 40 The hierarchical nature of protein architecture 41 Classification of protein structures 44 Protein structure prediction and engineering 51 Critical Assessment of Structure Prediction (CASP) 52 Protein engineering 52 Proteomics 52, DNA microarrays 53 Mass spectrometry 54 Systems biology 54 Clinical implications 55 The future 57 Recommended reading 57 Exercises, Problems, and Weblems 59 2 Genome organization and evolution 67 Genomes and proteomes 68 Genes 69 Proteomes 71 Eavesdropping on the transmission of genetic information 72 Mappings between the maps 77 High-resolution maps 78 Picking out genes in genomes 80 Genomes of prokaryotes 81 The genome of the bacterium Escherichia coil 82 The genome of the archaeon Methanococcusjannaschii 85 The genome of one of the simplest organisms: Mycoplasma genitalium 86 Genomes of eukaryotes 87 The genome of Saccharomyces cerevisiae (baker's yeast) 89 The genome of Caenorhabditis elegans 93 The genome of Drosophila melanogaster 94 The genome of Arabidopsis thaliana 95 The genome of Homo sapiens (the human genome) 96 Protein coding genes 97 Repeat sequences 99 RNA 100 Single-nucleotide polymorphisms (SNPs) 101 Genetic diversity in anthropology 102 Genetic diversity and personal identification 103 Genetic analysis of cattle domestication .104 Evolution of genomes 104 Please pass the genes: horizontal gene transfer 108 Comparative genomics of eukaryotes 109 Recommended reading 111 Exercises, Problems, and Weblems 112 3 Archives and information retrieval 117 Introduction 118 Database indexing and specification of search terms 118 Follow-up questions 120 Analysis of retrieved data 121 The archives 121 Nucleic acid sequence databases 122 Genome databases 124 Protein sequence databases 124 Databases of structures 128 Specialized, or'boutique' databases 135 Expression and proteomics databases 136 Databases of metabolic pathways 138 Bibliographic databases 139 Surveys of molecular biology databases and servers 139 Gateways to archives 140 Access to databases in molecular biology 141 ENTREZ 141 The Sequence Retrieval System (SRS) 148 The Protein Identification Resource (PIR) 149 ExPASy-Expert Protein Analysis System 150 Ensembl 151 Where do we go from here? 152 Recommended reading 152 Exercises, Problems, and Weblems 153 4 Alignments and phylogenetic trees 157 Introduction to sequence alignment 158 The dotplot 160 Dotplots and sequence alignments 165 Measures of sequence similarity 171 Scoring schemes 171 Computing the alignment of two sequences 175 Variations and generalizations 175 Approximate methods for quick screening of databases 176 The dynamic programming algorithm for optimal pairwise sequence alignment 176 Significance of alignments 182 Multiple sequence alignment 186 Applications of multiple sequence alignments to database searching 188 Profiles 189 PSI-BLAST 191 Hidden Markov Models 193 Phylogeny 198 Phylogenetic trees 203 Clustering methods 205 Cladistic methods 206 The problem of varying rates of evolution 207 Computational considerations 208 Recommended reading 209 Exercises, Problems, and Weblems 210 5 Protein structure and drug discovery 219 Introduction 220 Protein stability and folding 223 The Sasisekharan-Ramakrishnan-Ramachandran plot describes allowed mainchain conformations 223 The sidechains 225 Protein stability and denaturation 225 Protein folding 228 Applications of hydrophobicity 229 Superposition of structures, and structural alignments 233 DALI (Distance-matrix ALignment) 235 Evolution of protein structures 236 Classifications of protein structures 238 SCOP 239 Protein structure prediction and modelling 240 Critical Assessment of Structure Prediction (CASP) 242 Secondary structure prediction 244 Homology modelling 250 Fold recognition 252 Conformational energy calculations and molecular dynamics 255 ROSETTA 259 LINUS 259 Assignment of protein structures to genomes 263 Prediction of protein function 265 Divergence of function: orthologues and paralogues 266 Drug discovery and development 269 The lead compound 271 Bioinformatics in drug discovery and development 273 Recommended reading 284 Exercises, Problems, and Weblems 285 6 Proteomics and systems biology 291 DNA microarrays 293 Analysis of microarray data 295 Mass spectrometry 301 Identification of components of a complex mixture 301 Protein sequencing by mass spectrometry 304 Genome sequence analysis by mass spectrometry 306 Systems biology 311 Networks and graphs 313 Network structure and dynamics 318 Protein complexes and aggregates 320 Properties of protein-protein complexes 321 Protein interaction networks 324 Regulatory networks 329 Structures of regulatory networks 330 Structural biology of regulatory networks 336 Recommended reading 339 Exercises, Problems, and Weblems 339 Conclusions 345 Answers to Exercises 347 Glossary 353 Index 357 Colour plates
Summary: the second edition of Introduction to Bioinformatics introduces the student to the power of bioinformatics as a set of scientific tools. Retaining and enhancing the rich pedagogy and lucid presentation of the first edition, this new edition explains how to access the data archives of genomes and proteins, and the kind of questions these data and tools can answer. It also discusses how to make inferences from the data archives, how to make connections among them, and how to derive useful and interesting predictions. The book is accompanied by a fully integrated companion website.
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Includes bibliographical references and index.

1 Introduction 1
Life in space and time 3
Evolution is the change over time in the world of living things 4
Dogmas: central and peripheral 6
Observables and data archives. 9
Information flow in bioinformatics 12
Curation, annotation, and quality control 13
The World Wide Web 14
Electronic publication 15
Computers and computer science 16
Programming 17
Biological classification and nomenclature 21
Use of sequences to determine phylogenetic relationships 24
Use of SINES and LINES to derive phylogenetic relationships 30
Searching for similar sequences in databases: PSI-BLAST 32
Introduction to protein structure 40
The hierarchical nature of protein architecture 41
Classification of protein structures 44
Protein structure prediction and engineering 51
Critical Assessment of Structure Prediction (CASP) 52
Protein engineering 52
Proteomics 52,
DNA microarrays 53
Mass spectrometry 54
Systems biology 54
Clinical implications 55
The future 57
Recommended reading 57
Exercises, Problems, and Weblems 59
2 Genome organization and evolution 67
Genomes and proteomes 68
Genes 69
Proteomes 71



Eavesdropping on the transmission of genetic information 72
Mappings between the maps 77
High-resolution maps 78
Picking out genes in genomes 80
Genomes of prokaryotes 81
The genome of the bacterium Escherichia coil 82
The genome of the archaeon Methanococcusjannaschii 85
The genome of one of the simplest organisms: Mycoplasma
genitalium 86
Genomes of eukaryotes 87
The genome of Saccharomyces cerevisiae (baker's yeast) 89
The genome of Caenorhabditis elegans 93
The genome of Drosophila melanogaster 94
The genome of Arabidopsis thaliana 95
The genome of Homo sapiens (the human genome) 96
Protein coding genes 97
Repeat sequences 99
RNA 100
Single-nucleotide polymorphisms (SNPs) 101
Genetic diversity in anthropology 102
Genetic diversity and personal identification 103
Genetic analysis of cattle domestication .104
Evolution of genomes 104
Please pass the genes: horizontal gene transfer 108
Comparative genomics of eukaryotes 109
Recommended reading 111
Exercises, Problems, and Weblems 112
3 Archives and information retrieval 117
Introduction 118
Database indexing and specification of search terms 118
Follow-up questions 120
Analysis of retrieved data 121
The archives 121
Nucleic acid sequence databases 122
Genome databases 124
Protein sequence databases 124
Databases of structures 128
Specialized, or'boutique' databases 135
Expression and proteomics databases 136
Databases of metabolic pathways 138
Bibliographic databases 139
Surveys of molecular biology databases and servers 139
Gateways to archives 140
Access to databases in molecular biology 141



ENTREZ 141
The Sequence Retrieval System (SRS) 148
The Protein Identification Resource (PIR) 149
ExPASy-Expert Protein Analysis System 150
Ensembl 151
Where do we go from here? 152
Recommended reading 152
Exercises, Problems, and Weblems 153
4 Alignments and phylogenetic trees 157
Introduction to sequence alignment 158
The dotplot 160
Dotplots and sequence alignments 165
Measures of sequence similarity 171
Scoring schemes 171
Computing the alignment of two sequences 175
Variations and generalizations 175
Approximate methods for quick screening of databases 176
The dynamic programming algorithm for optimal pairwise sequence alignment 176
Significance of alignments 182
Multiple sequence alignment 186
Applications of multiple sequence alignments to database searching 188
Profiles 189
PSI-BLAST 191
Hidden Markov Models 193
Phylogeny 198
Phylogenetic trees 203
Clustering methods 205
Cladistic methods 206
The problem of varying rates of evolution 207
Computational considerations 208
Recommended reading 209
Exercises, Problems, and Weblems 210
5 Protein structure and drug discovery 219
Introduction 220
Protein stability and folding 223
The Sasisekharan-Ramakrishnan-Ramachandran plot describes
allowed mainchain conformations 223
The sidechains 225
Protein stability and denaturation 225
Protein folding 228
Applications of hydrophobicity 229
Superposition of structures, and structural alignments 233
DALI (Distance-matrix ALignment) 235



Evolution of protein structures 236
Classifications of protein structures 238
SCOP 239
Protein structure prediction and modelling 240
Critical Assessment of Structure Prediction (CASP) 242
Secondary structure prediction 244
Homology modelling 250
Fold recognition 252
Conformational energy calculations and molecular dynamics 255
ROSETTA 259
LINUS 259
Assignment of protein structures to genomes 263
Prediction of protein function 265
Divergence of function: orthologues and paralogues 266
Drug discovery and development 269
The lead compound 271
Bioinformatics in drug discovery and development 273
Recommended reading 284
Exercises, Problems, and Weblems 285
6 Proteomics and systems biology 291
DNA microarrays 293
Analysis of microarray data 295
Mass spectrometry 301
Identification of components of a complex mixture 301
Protein sequencing by mass spectrometry 304
Genome sequence analysis by mass spectrometry 306
Systems biology 311
Networks and graphs 313
Network structure and dynamics 318
Protein complexes and aggregates 320
Properties of protein-protein complexes 321
Protein interaction networks 324
Regulatory networks 329
Structures of regulatory networks 330
Structural biology of regulatory networks 336
Recommended reading 339
Exercises, Problems, and Weblems 339
Conclusions 345
Answers to Exercises 347
Glossary 353
Index 357
Colour plates

the second edition of Introduction to Bioinformatics introduces the student to the power of bioinformatics as a set of scientific tools. Retaining and enhancing the rich pedagogy and lucid presentation of the first edition, this
new edition explains how to access the data archives of genomes and proteins, and the kind of questions these data and tools can answer. It also discusses how to make inferences from the data archives, how to make connections among them, and how to derive useful and interesting predictions. The book
is accompanied by a fully integrated companion website.

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