Proteomics - Technologies, Markets and Companies

Table of Contents

0. Executive Summary 15

1. Basics of Proteomics 17

• Introduction 17
• History 17
• Nucleic acids, genes and proteins 18
• Genome 18
• DNA 19
• RNA 19
• MicroRNAs 19
• Decoding of mRNA by the ribosome 20
• Genes 20
• Alternative splicing 20
• Transcription 21
• Gene regulation 22
• Gene expression 22
• Chromatin 23
• Proteins 23
• Spliceosome 23
• Functions of proteins 24
• Inter-relationship of protein, mRNA and DNA 24
• Proteomics 25
• Mitochondrial proteome 26
• S-nitrosoproteins in mitochondria 27
• Proteomics and genomics 27
• Classification of proteomics 30
• Levels of functional genomics and various "omics" 30
• Glycoproteomics 30
• Transcriptomics 31
• Metabolomics 31
• Cytomics 31
• Phenomics 31
• Proteomics and systems biology 32

2. Proteomic Technologies 33

• Key technologies driving proteomics 33
• Sample preparation 34
• New trends in sample preparation 34
• Pressure Cycling Technology 35
• Protein separation technologies 35
• High resolution 2D gel electrophoresis 35
• Variations of 2D gel technology 36
• Limitations of 2DGE and measures to overcome these 36
• 1-D sodium dodecyl sulfate (SDS) PAGE 36
• Capillary electrophoresis systems 37
• Head column stacking capillary zone electrophoresis 37
• Removal of albumin and IgG 37
• Companies with protein separation technologies 38
• Protein detection 39
• Protein identification and characterization 39
• Mass spectrometry (MS) 39
• Companies involved in mass spectrometry 40
• Electrospray ionization 41
• Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 42
• Cryogenic MALDI- Fourier Transform Mass Spectrometry 43
• Stable-isotope-dilution tandem mass spectrometry 44
• HUPO Gold MS Protein Standard 44
• High performance liquid chromatography 44
• Multidimensional protein identification technology (MudPIT) 44
• Peptide mass fingerprinting 45
• Combination of protein separation technologies with mass spectrometry 45
• Combining capillary electrophoresis with mass spectrometry 45
• 2D PAGE and mass spectrometry 45
• Quantification of low abundance proteins 46
• SDS-PAGE 46
• Antibodies and proteomics 47
• Detection of fusion proteins 47
• Labeling and detection of proteins 47
• Fluorescent labeling of proteins in living cells 48
• Combination of microspheres with fluorescence 48
• Self-labeling protein tags 48
• Analysis of peptides 49
• Differential Peptide Display 49
• Peptide analyses using NanoLC-MS 50
• Protein sequencing 51
• Real-time PCR for protein quantification 51
• MS-based quantitative proteomics 52
• Functional proteomics: technologies for studying protein function 52
• Functional genomics by mass spectrometry 52
• RNA-Protein fusions 53
• Designed repeat proteins 53
• Application of nanbiotechnology to proteomics 53
• Nanoproteomics 54
• Protein nanocrystallography 54
• Single-molecule mass spectrometry using a nanopore 54
• Nanoelectrospray ionization 55
• Nanoparticle barcodes 55
• Biobarcode assay for proteins 56
• Resonance Light Scattering technology 57
• Nanoscale protein analysis 57
• Nanobiotechnology for discovery of protein biomarkers in the blood 58
• Study of single membrane proteins at subnanometer resolution 58
• Nanotube-vesicle networks for study of membrane proteins 58
• Qdot-nanocrystals 59
• Nanotube electronic biosensor 59
• A nanoscale mechanism for protein engineering 59
• Protein expression profiling 60
• Cell-based protein assays 60
• Living cell-based assays for protein function 61
• Companies developing cell-based protein assays 61
• Protein function studies 62
• Transcriptionally Active PCR 62
• Protein-protein interactions 62
• Yeast two-hybrid system 64
• Membrane one-hybrid method 65
• Protein affinity chromatography 66
• Phage display 66
• Fluorescence Resonance Energy Transfer 66
• Bioluminescence Resonance Energy Transfer 66
• Detection Enhanced Ubiquitin Split Protein Sensor technology 67
• Protein-fragment complementation system 67
• In vivo study of protein-protein interactions 67
• Computational prediction of interactions 68
• Interactome 68
• Protein-protein interactions and drug discovery 69
• Companies with technologies for protein-protein interaction studies 69
• Protein-DNA interaction 70
• Determination of protein structure 71
• X-Ray crystallography 71
• Nuclear magnetic resonance 72
• Electron spin resonance 73
• Prediction of protein structure 73
• Protein tomography 73
• X-ray scattering-based method for determining the structure of proteins 74
• Prediction of protein function 74
• Three-dimensional proteomics for determination of function 75
• An algorithm for genome-wide prediction of protein function 75
• Monitoring protein function by expression profiling 76
• Isotope-coded affinity tag peptide labeling 76
• Differential Proteomic Panning 77
• Cell map proteomics 77
• Topological proteomics 77
• Organelle or subcellular proteomics 78
• Nucleolar proteomics 79
• Glycoproteomic technologies 79
• High-sensitivity glycoprotein analysis 79
• Fluorescent in vivo imaging of glycoproteins 79
• Integrated approaches for protein characterization 80
• Imaging mass spectrometry 80
• IMS technologies 80
• Applications of IMS 81
• The protein microscope 81
• Automation and robotics in proteomics 82
• Laser capture microdissection 82
• Microdissection techniques used for proteomics 82
• Uses of LCM in combination with proteomic technologies 83
• Concluding remarks about applications of proteomic technologies 83
• Precision proteomics 84

3. Protein biochip technology 85

• Introduction 85
• Types of protein biochips 86
• ProteinChip 86
• Applications and advantages of ProteinChip 87
• ProteinChip Biomarker System 87
• Matrix-free ProteinChip Array 88
• Aptamer-based protein biochip 88
• Fluorescence planar wave guide technology-based protein biochips 89
• Lab-on-a-chip for protein analysis 89
• Microfluidic biochips for proteomics 90
• Protein biochips for high-throughput expression 91
• Nucleic Acid-Programmable Protein Array 91
• High-density protein microarrays 91
• HPLC-Chip for protein identification 91
• Antibody microarrays 92
• Integration of protein array and image analysis 92
• Tissue microarray technology for proteomics 92
• Protein biochips in molecular diagnostics 93
• A force-based protein biochip 94
• L1 chip and lipid immobilization 94
• Multiplexed Protein Profiling on Microarrays 94
• Live cell microarrays 95
• ProteinArray Workstation 95
• Proteome arrays 96
• The Yeast ProtoArray 96
• ProtoArray™ Human Protein Microarray 96
• TRINECTIN proteome chip 97
• Peptide arrays 97
• Surface plasmon resonance technology 98
• Biacore' s SPR 98
• FLEX CHIP 98
• Combination of surface plasmon resonance and MALDI-TOF 99
• Protein chips/microarrays using nanotechnology 99
• Nanoparticle protein chip 99
• Protein nanobiochip 99
• Protein nanoarrays 100
• Self-assembling protein nanoarrays 100
• Companies involved in protein biochip/microarray technology 101

4. Bioinformatics in Relation to Proteomics 105

• Introduction 105
• Bioinformatic tools for proteomics 105
• Testing of SELDI-TOF MS Proteomic Data 105
• BioImagine' s ProteinMine 106
• Bioinformatics for pharmaceutical applications of proteomics 106
• In silico search of drug targets by Biopendium 106
• Compugen' s LEADS 107
• DrugScore 107
• Proteochemometric modeling 107
• Integration of genomic and proteomic data 108
• Proteomic databases: creation and analysis 109
• Introduction 109
• Proteomic databases 109
• GenProtEC 110
• Human Protein Atlas 110
• Human Proteomics Initiative 111
• International Protein Index 111
• Proteome maps 112
• Protein Structure Initiative - Structural Genomics Knowledgebase 112
• Protein Warehouse Database 112
• Protein Data Bank 112
• Universal Protein Resource 113
• Protein interaction databases 113
• Biomolecular Interaction Network Database 114
• ENCODE 114
• Functional Genomics Consortium 115
• Human Proteinpedia 115
• ProteinCenter 115
• Databases of the National Center for Biotechnology Information 116
• Bioinformatics for protein identification 116
• Application of bioinformatics in functional proteomics 116
• Use of bioinformatics in protein sequencing 116
• Bottom-up protein sequencing 117
• Top-down protein sequencing 118
• Protein structural database approach to drug design 118
• Bioinformatics for high-throughput proteomics 118
• Companies with bioinformatic tools for proteomics 119

5. Research in Proteomics 121

• Introduction 121
• Applications of proteomics in biological research 121
• Identification of novel human genes by comparative proteomics 121
• Study of relationship between genes and proteins 122
• Structural genomics or structural proteomics 122
• Protein Structure Factory 123
• Protein Structure Initiative 124
• Studies on protein structure at Argonne National Laboratory 124
• Structural Genomics Consortium 125
• Protein knockout 125
• Antisense approach and proteomics 125
• RNAi and protein knockout 126
• Total knockout of cellular proteins 126
• Ribozymes and proteomics 126
• Single molecule proteomics 127
• Single-molecule photon stamping spectroscopy 127
• Single nucleotide polymorphism determination by TOF-MS 127
• Application of proteomic technologies in systems biology 128
• Signaling pathways and proteomics 128
• Kinomics 128
• Combinatorial RNAi for quantitative protein network analysis 129
• Proteomics in neuroscience research 129
• Stem cell proteomics 130
• hESC phosphoproteome 130
• Proteomic studies of mesenchymal stem cells 130
• Proteomics of neural stem cells 131
• Proteome Biology of Stem Cells Initiative 132
• Proteomic analysis of the cell cycle 132
• Nitric oxide and proteomics 132
• A proteomic method for identification of cysteine S-nitrosylation sites 133
• Study of the nitroproteome 133
• Study of the phosphoproteome 133
• Study of the mitochondrial proteome 134
• Proteomic technologies for study of mitochondrial proteomics 134
• Cryptome 135
• Study of protein transport in health and disease 135
• Proteomics research in the academic sector 135
• Vanderbilt University' s Center for Proteomics and Drug Actions 137
• ProteomeBinders initiative 137

6. Pharmaceutical Applications of Proteomics 139

• Introduction 139
• Current drug discovery process and its limitations 139
• Role of omics in drug discovery 140
• Genomics-based drug discovery 140
• Metabolomics technologies for drug discovery 141
• Role of metabonomics in drug discovery 141
• Basis of proteomics approach to drug discovery 142
• Proteins and drug action 142
• Transcription-aided drug design 143
• Role of proteomic technologies in drug discovery 143
• Liquid chromatography-based drug discovery 144
• Capture compound mass spectrometry 145
• Protein-expression mapping by 2DGE 145
• Role of MALDI mass spectrometry in drug discovery 145
• Tissue imaging mass spectrometry 145
• Companies using MALDI for drug discovery 147
• Oxford Genome Anatomy Project 147
• Proteins as drug targets 148
• Ligands to capture the purine binding proteome 148
• Chemical probes to interrogate key protein families for drug discovery 149
• Global proteomics for pharmacodynamics 149
• CellCartaR proteomics platform 149
• ZeptoMARK™ protein profiling system 150
• Role of proteomics in targeting disease pathways 151
• Identification of protein kinases as drug targets 151
• Mechanisms of action of kinase inhibitors 151
• G-protein coupled receptors as drug targets 152
• Methods of study of GPCRs 152
• Cell-based assays for GPCR 152
• Companies involved in GPCR-based drug discovery 153
• GPCR localization database 154
• Matrix metalloproteases as drug targets 154
• PDZ proteins as drug targets 155
• Proteasome as drug target 155
• Serine hydrolases as drug targets 156
• Targeting mTOR signaling pathway 156
• Targeting caspase-8 for anticancer therapeutics 157
• Bioinformatic analysis of proteomics data for drug discovery 158
• Drug design based on structural proteomics 158
• Protein crystallography for determining 3D structure of proteins 158
• Automated 3D protein modeling 159
• Drug targeting of flexible dynamic proteins 159
• Companies involved in structure-based drug-design 159
• Integration of genomics and proteomics for drug discovery 160
• Ligand-receptor binding 161
• Role of proteomics in study of ligand-receptor binding 161
• Aptamer protein binding 162
• Systematic Evolution of Ligands by Exponential Enrichment 162
• Aptamers and high-throughput screening 162
• Nucleic Acid Biotools 163
• Aptamer beacons 163
• Peptide aptamers 164
• Riboreporters for drug discovery 164
• Target identification and validation 164
• Application of mass spectrometry for target identification 165
• Gene knockout and gene suppression for validating protein targets 165
• Laser-mediated protein knockout for target validation 165
• Integrated proteomics for drug discovery 166
• High-throughput proteomics 166
• Companies involved in high-throughput proteomics 167
• Drug discovery through protein-protein interaction studies 167
• Protein-protein interaction as basis for drug target identification 168
• Protein-PCNA interaction as basis for drug design 168
• Two-hybrid protein interaction technology for target identification 169
• Biosensors for detection of small molecule-protein interactions 169
• Protein-protein interaction maps 170
• ProNet (Myriad Genetics) 170
• Hybrigenics' maps of protein-protein interactions 170
• CellZome' s functional map of protein-protein interactions 171
• Mapping of protein-protein interactions by mass spectrometry 172
• Protein interaction map of Drosophila melanogaster 172
• Protein-interaction map of Wellcome Trust Sanger Institute 172
• Protein-protein interactions as targets for therapeutic intervention 172
• Inhibition of protein-protein interactions by peptide aptamers 173
• Selective disruption of proteins by small molecules 173
• Post-genomic combinatorial biology approach 173
• Differential proteomics 174
• Shotgun proteomics 174
• Chemogenomics/chemoproteomics for drug discovery 175
• Chemoproteomics-based drug discovery 176
• Companies involved in chemogenomics/chemoproteomics 177
• Activity-based proteomics 178
• Iconix' s DrugMatrix 178
• Locus Discovery technology 178
• Automated ligand identification system 179
• Expression proteomics: protein level quantification 180
• Role of phage antibody libraries in target discovery 180
• Analysis of posttranslational modification of proteins by MS 180
• Phosphoproteomics for drug discovery 181
• Application of glycoproteomics for drug discovery 181
• Role of carbohydrates in proteomics 181
• Challenges of glycoproteomics 182
• Companies involved in glycoproteomics 182
• Role of protein microarrays/ biochips for drug discovery 183
• Protein microarrays vs DNA microarrays for high-throughput screening 183
• BIA-MS biochip for protein-protein interactions 184
• ProteinChip with Surface Enhanced Neat Desorption 184
• Protein-domains microarrays 184
• Some limitations of protein biochips 185
• Concluding remarks about role of proteomics in drug discovery 185
• RNA versus protein profiling as guide to drug development 186
• RNA as drug target 186
• Combination of RNA and protein profiling 187
• RNA binding proteins 187
• Toxicoproteomics 187
• Hepatotoxicity 187
• Nephrotoxicity 188
• Cardiotoxicity 189
• Neurotoxicity 189
• Protein/peptide therapeutics 189
• Peptide-based drugs 189
• PhylomerR peptides 190
• Cryptein-based therapeutics 190
• Synthetic proteins and peptides as pharmaceuticals 191
• Genetic immunization and proteomics 191
• Proteomics and gene therapy 192
• Role of proteomics in clinical drug development 192
• Pharmacoproteomics 193
• Role of proteomics in clinical drug safety 193

7. Application of Proteomics in Human Healthcare 195

• Clinical proteomics 196
• Definition and standards 196
• Vermillion' s Clinical Proteomics Program 196
• Pathophysiology of human diseases 197
• Diseases due to misfolding of proteins 197
• Mechanism of protein folding 198
• Nanoproteomics for study of misfolded proteins 199
• Therapies for protein misfolding 199
• Intermediate filament proteins 200
• Significance of mitochondrial proteome in human disease 201
• Proteome of Saccharomyces cerevisiae mitochondria 201
• Rat mitochondrial proteome 201
• Proteomic approaches to biomarker identification 202
• The ideal biomarker 202
• Proteomic technologies for biomarker discovery 202
• MALDI mass spectrometry for biomarker discovery 203
• BAMF™ Technology 203
• Protein biochips/microarrays and biomarkers 204
• Antibody-based biomarker discovery 204
• Tumor-specific serum peptidome patterns 204
• Search for protein biomarkers in body fluids 205
• Challenges and strategies for discovey of protein biomarkers in plasma 205
• 3-D structure of CD38 as a biomarker 206
• BD"! Free Flow Electrophoresis System 206
• Isotope tags for relative and absolute quantification 207
• Plasma protein microparticles as biomarkers 207
• Proteome partitioning 208
• Stable isotope tagging methods 208
• Technology to measure both the identity and size of the biomarker 208
• SISCAPA method for quantitating proteins and peptides in plasma 209
• Biomarkers in the urinary proteome 209
• Application of proteomics in molecular diagnosis 209
• Proximity ligation assay 210
• Protein patterns 211
• Proteomic tests on body fluids 211
• Cyclical amplification of proteins 212
• Applications of proteomics in infections 213
• Role of proteomics in virology 213
• Study of interaction of proteins with viruses 214
• Role of proteomics in bacteriology 214
• Epidemiology of bacterial infections 214
• Proteomic approach to bacterial pathogenesis 215
• Vaccines for bacterial infections 215
• Protein profiles associated with bacterial drug resistance 215
• Analyses of the parasite proteome 216
• Application of proteomics in cystic fibrosis 216
• Oncoproteomics 216
• Application of CellCarta technology for oncology 218
• Accentuation of differentially expressed proteins using phage technology 218
• Identification of oncogenic tyrosine kinases using phosphoproteomics 218
• Single-cell protein expression analysis by microfluidic techniques 219
• Dynamic cell proteomics in response to a drug 219
• Desorption electrospray ionization for cancer diagnosis 219
• Proteomic analysis of cancer cell mitochondria 219
• Mass spectrometry for identification of oncogenic chimeric proteins 220
• Id proteins as targets for cancer therapy 220
• Proteomic study of p53 221
• Human Tumor Gene Index 221
• Integration of cancer genomics and proteomics 221
• Laser capture microdissection technology and cancer proteomics 222
• Cancer tissue proteomics 222
• Use of proteomics in cancers of various organ systems 223
• Proteomics of brain tumors 223
• Proteomics of breast cancer 224
• Proteomics of colorectal cancer 225
• Proteomics of esophageal cancer 225
• Proteomics of hepatic cancer 226
• Proteomics of leukemia 226
• Proteomics of lung cancer 227
• Proteomics of pancreatic cancer 227
• Proteomics of prostate cancer 228
• Diagnostic use of cancer biomarkers 228
• NCI' s Network of Clinical Proteomic Technology Centers for Cancer Research 230
• Proteomics and tumor immunology 231
• Proteomics and study of tumor invasiveness 232
• Anticancer drug discovery and development 232
• Kinase-targeted drug discovery in oncology 232
• Anticancer drug targeting: functional proteomics screen of proteases 233
• Small molecule inhibitors of cancer-related proteins 233
• Role of proteomics in studying drug resistance in cancer 234
• Future prospects of oncoproteomics 234
• Companies involved in application of proteomics to oncology 234
• Application of proteomics in neurological disorders 235
• Neuroproteomics 235
• Prion diseases 236
• Proteomics and transmissible spongiform encephalopathies 237
• Proteomics and neurodegenerative disorders 238
• Detection of misfolded proteins 240
• Proteomics and glutamate repeat disorders 240
• Proteomics and Huntington' s disease 240
• Proteomics and Parkinson' s disease 241
• Proteomics and Alzheimer' s disease 241
• Common denominators of Alzheimer' s and prion diseases 242
• Ion channel link for protein-misfolding disease 243
• Proteomics and demyelinating diseases 243
• Proteomics of amyotrophic lateral sclerosis 243
• Proteomics of spinal muscular atrophy 244
• Proteomics of Fabry disease 244
• Proteomics and GM1 gangliosidosis 244
• Proteomics of CNS trauma 245
• Proteomics of CNS aging 246
• Neuroproteomics of psychiatric disorders 246
• Neuroproteomic of cocaine addiction 247
• Neurodiagnostics based on proteomics 247
• Testing for disease-specific proteins in the cerebrospinal fluid 247
• Tau proteins 248
• CNS tissue proteomics 249
• Diagnosis of CNS disorders by examination of proteins in urine 250
• Diagnosis of CNS disorders by examination of proteins in the blood 250
• Serum pNF-H as biomarker of CNS damage 251
• Proteomics of BBB 252
• Future prospects of neuroproteomics in neurology 252
• HUPO' s Pilot Brain Proteome Project 253
• Proteomics of cardiac disorders 253
• Study of cardiac mitochondrial proteome in myocardial ischemia 254
• Cardiac protein databases 254
• Proteomics of dilated cardiomyopathy and heart failure 254
• Role of proteomics in heart transplantation 255
• Future of application of proteomics in cardiology 255
• Proteomic technologies for research in pulmonary disorders 255
• Application fo proteomics in renal disorders 257
• Diagnosis of renal disorders 257
• Proteomic biomarkers of acute kidney injury 257
• Cystatin C as biomarker of glomerular filtration rate 257
• Protein biomarkers of nephritis 258
• Proteomics and kidney stones 258
• Proteomics of eye disorders 258
• Retinal dystrophies 259
• Use of proteomics in inner ear disorders 259
• Use of proteomics in aging research 260
• Removal of altered cellular proteins in aging 260
• Proteomics and nutrition 261

8. Commercial Aspects of Proteomics 263

• Introduction 263
• Potential markets for proteomic technologies 263
• Geographical distribution of proteomics technologies markets 264
• Markets for protein separation technologies 264
• Markets for 2D gel electrophoresis 265
• Trends in protein separation technolgies and effect on market 265
• Protein biochip markets 265
• Mass spectrometry markets 266
• Markets for MALDI for drug discovery 266
• Markets for nuclear magnetic resonance spectroscopy 266
• Market for structure-based drug design 267
• Bioinformatics markets for proteomics 267
• Markets for protein biomarkers 267
• Markets for cell-based protein assays 267
• Business and strategic considerations 268
• Cost of protein structure determination 268
• Opinion surveys of the scientist consumers of proteomic technologies 268
• Opinions on mass spectrometry 268
• Opinions on bioinformatics and proteomic databases 268
• Systems for in vivo study of protein-protein interactions 269
• Perceptions of the value of protein biochip/microfluidic systems 269
• Small versus big companies 269
• Expansion in proteomics according to area of application 269
• Growth trends in cell-based protein assay market 270
• Challenges for development of cell-based protein assays 270
• Future trends and prospects of cell-based protein assays 270
• Strategic collaborations 271
• Analysis of proteomics collaborations according to types of companies 271
• Types of proteomic collaborations 272
• Proteomics collaborations according to application areas 272
• Analysis of proteomics collaborations: types of technologies 272
• Collaborations based on protein biochip technology 273
• Concluding remarks about proteomic collaborations 273
• Proteomic patents 274
• Market drivers in proteomics 274
• Needs of the pharmaceutical industry 274
• Need for outsourcing proteomic technologies 275
• Funding of proteomic companies and research 275
• Technical advances in proteomics 275
• Changing trends in healthcare in future 276
• Challenges facing proteomics 276
• Magnitude and complexity of the task 276
• Technical challenges 276
• Limitations of proteomics 277
• Limitations of 2DGE 277
• Limitations of mass spectrometry techniques 277
• Complexity of the pharmaceutical proteomics 277
• Unmet needs in proteomics 278

9. Future of Proteomics 279

• Genomics to proteomics 279
• Faster technologies 279
• FLEXGene repository 279
• Need for new proteomic technologies 280
• Emerging proteomic technologies 281
• Detection of alternative protein isoforms 281
• Direct protein identification in large genomes by mass spectrometry 281
• Proteome identification kits with stacked membranes 281
• Vacuum deposition interface 282
• In vitro protein biosynthesis 282
• Proteome mining with adenosine triphosphate 282
• Proteome-scale purification of human proteins from bacteria 282
• Proteostasis network 283
• Cytoproteomics 283
• Subcellular proteomics 283
• Individual cell proteomics 284
• Live cell proteomics 284
• Fluorescent proteins for live-cell imaging 285
• Membrane proteomics 285
• Identification of membrane proteins by tandem MS of protein ions 285
• Solid state NMR for study of nanocrystalline membrane proteins 286
• Multiplex proteomics 286
• High-throughput for proteomics 286
• Future directions for protein biochip application 287
• Bioinformatics for proteomics 287
• High-Throughput Crystallography Consortium 287
• Study of protein folding by IBM' s Blue Gene 288
• Study of proteins by atomic force microscopy 288
• Population proteomics 288
• Comparative proteome analysis 289
• Human Proteome Organization 289
• Human Salivary Proteome 290
• Academic-commercial collaborations in proteomics 290
• Indiana Centers for Applied Protein Sciences 290
• Role of proteomics in the healthcare of the future 291
• Proteomics and molecular medicine 291
• Proteodiagnostics 291
• Proteomics and personalized medicine 292
• Targeting the ubiquitin pathway for personalized therapy of cancer 292
• Protein patterns and personalized medicine 292
• Personalizing interferon therapy of hepatitis C virus 294
• Protein biochips and personalized medicine 294
• Combination of diagnostics and therapeutics 295
• Future prospects 295

10. References 297

Tables

• Table 1 1: Landmarks in the evolution of proteomics 17
• Table 1 2: Comparison of DNA and protein 24
• Table 1 3: Comparison of mRNA and protein 25
• Table 1 4: Methods of analysis at various levels of functional genomics 30
• Table 2 1: Proteomics technologies 33
• Table 2 2: Protein separation technologies of selected companies 38
• Table 2 3: Companies supplying mass spectrometry instruments 40
• Table 2 4: Companies involved in cell-based protein assays 61
• Table 2 5: Methods used for the study of protein-protein interactions 63
• Table 2 6: A selection of companies involved in protein-protein interaction studies 69
• Table 2 7: Proteomic technologies used with laser capture microdissection 83
• Table 3 1: Applications of protein biochip technology 85
• Table 3 2: Selected companies involved in protein biochip/microarray technology 101
• Table 4 1: Proteomic databases and other Internet sources of proteomics information 109
• Table 4 2: Protein interaction databases available on the Internet 113
• Table 4 3: Bioinformatic tools for proteomics from academic sources 119
• Table 4 4: Selected companies involved in bioinformatics for proteomics 120
• Table 5 1: Applications of proteomics in basic biological research 121
• Table 5 2: A sampling of proteomics research projects in academic institutions 135
• Table 6 1: Pharmaceutical applications of proteomics 139
• Table 6 2: Selected companies relevant to MALDI-MS for drug discovery 147
• Table 6 3: Selected companies involved in GPCR-based drug discovery 153
• Table 6 4: Companies involved in drug design based on structural proteomics 159
• Table 6 5: Proteomic companies with high-throughput protein expression technologies 167
• Table 6 6: Selected companies involved in chemogenomics/chemoproteomics 177
• Table 6 7: Companies involved in glycoproteomic technologies 182
• Table 7 1: Applications of proteomics in human healthcare 195
• Table 7 2: Companies involved in applications of proteomics to oncology 234
• Table 7 3: Neurodegenerative diseases with underlying protein abnormality 238
• Table 7 4: Disease-specific proteins in the cerebrospinal fluid of patients 247
• Table 7 5: Eye disorders and proteomic approaches 259
• Table 8 1: Potential markets for proteomic technologies 2008-2018 263
• Table 8 2: Geographical distribution of markets for proteomic technologies 2008-2018 264
• Table 8 3: 2008 revenues of major companies from protein separation technologies 264
• Table 9 1: Role of proteomics in personalizing strategies for cancer therapy 292

Figures

• Figure 1 1: Relationship of DNA, RNA and protein in the cell 25
• Figure 1 2: Protein production pathway from gene expression to functional protein with controls. 28
• Figure 1 3: Parallels between functional genomics and proteomics 28
• Figure 2 1: Proteomics: flow from sample preparation to characterization 34
• Figure 2 2: The central role of spectrometry in proteomics 40
• Figure 2 3: Electrospray ionization (ESI) 41
• Figure 2 4: Matrix-Assisted Laser Desorption/Ionization (MALDI) 42
• Figure 2 5: Scheme of bio-bar-code assay 56
• Figure 2 6: A diagrammatic presentation of yeast two-hybrid system 64
• Figure 3 1: ProteinChip System 87
• Figure 3 2: Surface plasma resonance (SPR) 98
• Figure 4 1: Role of bioinformatics in integrating genomic/proteomic-based drug discovery 108
• Figure 4 2: Bottom-up and top-down approaches for protein sequencing 117
• Figure 6 1: Drug discovery process 140
• Figure 6 2: Regulatory changes induced by drugs and implemented at the proteins level 143
• Figure 6 3: Relation of proteome to genome, diseases and drugs 144
• Figure 6 4: The mTOR pathways 157
• Figure 6 5: Steps in shotgun proteomics 175
• Figure 6 6: Chemogenomic approach to drug discovery (3-Dimensional Pharmaceuticals) 176
• Figure 7 1: Relation of oncoproteomics to other technologies 217
• Figure 7 2: A scheme of proteomics applications in CNS drug discovery and development 253
• Figure 8 1: Types of companies involved in proteomics collaborations 271
• Figure 8 2: Types of collaborations: R & D, licensing or marketing 272
• Figure 8 3: Proteomics collaborations according to application areas 272
• Figure 8 4: Proteomics collaborations according to technologies 273
• Figure 8 5: Unmet needs in proteomics 278
• Figure 9 1: A scheme of the role of proteomics in personalized management of cancer 294