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시장보고서
Proteomics - Technologies, Markets and Companies
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Abstract
Summary
This report describes and evaluates the proteomic technologies that will play
an important role in drug discovery, molecular diagnostics and practice of
medicine in the post-genomic era - the first decade of the 21st century. Most
commonly used technologies are 2D gel electrophoresis for protein separation
and analysis of proteins by mass spectrometry. Microanalytical protein
characterization with multidimentional liquid chromatography/mass spectrometry
improves the throughput and reliability of peptide mapping. Matrix-Assisted
Laser Desorption Mass Spectrometry (MALDI-MS) has become a widely used method
for determination of biomolecules including peptides, proteins. Functional
proteomics technologies include yeast two-hybrid system for studying protein-
protein interactions. Establishing a proteomics platform in the industrial
setting initially requires implementation of a series of robotic systems to
allow a high-throughput approach for analysis and identification of
differences observed on 2D electrophoresis gels. Protein chips are also
proving to be useful. Proteomic technologies are now being integrated into the
drug discovery process as complimentary to genomic approaches.
Toxicoproteomics, i.e. the evaluation of protein expression for understanding
of toxic events, is an important application of proteomics in preclincial drug
safety. Use of bioinformatics is essential for analyzing the massive amount of
data generated from both genomics and proteomics.
Proteomics is providing a better understanding of pathomechanisms of human
diseases. Analysis of different levels of gene expression in healthy and
diseased tissues by proteomic approaches is as important as the detection of
mutations and polymorphisms at the genomic level and may be of more value in
designing a rational therapy. Protein distribution / characterization in body
tissues and fluids, in health as well as in disease, is the basis of the use
of proteomic technologies for molecular diagnostics. Proteomics will play an
important role in medicine of the future which will be personalized and will
combine diagnostics with therapeutics. Important areas of application include
cancer (oncoproteomics) and neurological disorders (neuroproteomics). The text
is supplemented with 43 tables, 27 figures and over 500 selected references
from the literature.
The number of companies involved in proteomics has increased remarkably during
the past few years. More than 300 companies have been identified to be
involved in proteomics and 217 of these are profiled in the report with 478
collaborations.
The markets for proteomic technologies are difficult to estimate as they are
not distinct but overlap with those of genomics, gene expression, high
throughput screening, drug discovery and molecular diagnostics. Markets for
proteomic technologies are analyzed for the year 2011 and are projected to
years 2016 and 2021. The largest expansion will be in bioinformatics and
protein biochip technologies. Important areas of application are cancer and
neurological disorders
Table of Contents
Part I
0. Executive Summary 17
1. Basics of Proteomics 19
- Introduction 19
- History 19
- Nucleic acids, genes and proteins 20
- Genome 20
- DNA 21
- RNA 21
- MicroRNAs 21
- Decoding of mRNA by the ribosome 22
- Genes 23
- Alternative splicing 23
- Transcription 24
- Gene regulation 24
- Gene expression 25
- Chromatin 25
- Golgi complex 26
- Proteins 26
- Spliceosome 27
- Functions of proteins 27
- Inter-relationship of protein, mRNA and DNA 28
- Proteomics 29
- Mitochondrial proteome 30
- S-nitrosoproteins in mitochondria 30
- Proteomics and genomics 31
- Classification of proteomics 33
- Levels of functional genomics and various "omics" 33
- Glycoproteomics 34
- Transcriptomics 34
- Metabolomics 34
- Cytomics 35
- Phenomics 35
- Proteomics and systems biology 35
- Functional synthetic proteins 36
2. Proteomic Technologies 37
- Key technologies driving proteomics 37
- Sample preparation 38
- New trends in sample preparation 38
- Pressure Cycling Technology 39
- Protein separation technologies 39
- High resolution 2DGE 39
- Variations of 2D gel technology 40
- Limitations of 2DGE and measures to overcome these 40
- 1-D sodium dodecyl sulfate (SDS) PAGE 40
- Capillary electrophoresis systems 41
- Head column stacking capillary zone electrophoresis 41
- Removal of albumin and IgG 41
- Companies with protein separation technologies 42
- Protein purification 43
- Technologies for protein purification 43
- Applications of protein purification 44
- Protein detection 44
- Protein identification and characterization 44
- Mass spectrometry (MS) 44
- Companies involved in mass spectrometry 45
- Electrospray ionization 46
- Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 47
- Cryogenic MALDI- Fourier Transform Mass Spectrometry 48
- Stable-isotope-dilution tandem mass spectrometry 49
- HUPO Gold MS Protein Standard 49
- High performance liquid chromatography 49
- Multidimensional protein identification technology (MudPIT) 49
- Peptide mass fingerprinting 50
- Combination of protein separation technologies with mass spectrometry 50
- Combining capillary electrophoresis with mass spectrometry 50
- 2D PAGE and mass spectrometry 50
- Quantification of low abundance proteins 51
- SDS-PAGE 51
- Antibodies and proteomics 52
- Detection of fusion proteins 52
- Labeling and detection of proteins 52
- Fluorescent labeling of proteins in living cells 53
- Combination of microspheres with fluorescence 53
- Self-labeling protein tags 53
- Analysis of peptides 54
- C-terminal peptide analysis 54
- Differential Peptide Display 55
- Peptide analyses using NanoLC-MS 55
- Protein sequencing 56
- Real-time PCR for protein quantification 57
- Quantitative proteomics 57
- MS-based quantitative proteomics 57
- MS and cryo-electron tomography 57
- Functional proteomics: technologies for studying protein function 58
- Functional genomics by mass spectrometry 58
- RNA-Protein fusions 58
- Designed repeat proteins 58
- Application of nanbiotechnology to proteomics 59
- Nanoproteomics 59
- Protein nanocrystallography 59
- Single-molecule mass spectrometry using a nanopore 60
- Nanoelectrospray ionization 60
- Nanoparticle barcodes 61
- Biobarcode assay for proteins 61
- Nanoproteomics for discovery of protein biomarkers in the blood 62
- Nanoscale protein analysis 62
- Nanoscale mechanism for protein engineering 63
- Nanotube electronic biosensor 63
- Nanotube-vesicle networks for study of membrane proteins 64
- Nanowire transistor for the detection of protein-protein interactions 64
- Qdot-nanocrystals 64
- Resonance Light Scattering technology 65
- Study of single membrane proteins at subnanometer resolution 65
- Protein expression profiling 65
- Cell-based protein assays 66
- Living cell-based assays for protein function 67
- Companies developing cell-based protein assays 67
- Protein function studies 68
- Transcriptionally Active PCR 68
- Protein-protein interactions 68
- Yeast two-hybrid system 70
- Membrane one-hybrid method 71
- Protein affinity chromatography 71
- Phage display 71
- Fluorescence Resonance Energy Transfer 72
- Bioluminescence Resonance Energy Transfer 72
- Detection Enhanced Ubiquitin Split Protein Sensor technology 72
- Protein-fragment complementation system 73
- In vivo study of protein-protein interactions 73
- Computational prediction of interactions 74
- Interactome 74
- Protein-protein interactions and drug discovery 75
- Companies with technologies for protein-protein interaction studies 75
- Protein-DNA interaction 76
- Determination of protein structure 76
- X-Ray crystallography 77
- Nuclear magnetic resonance 78
- Electron spin resonance 78
- Prediction of protein structure 78
- Protein tomography 79
- X-ray scattering-based method for determining the structure of proteins
80
- Prediction of protein function 80
- Three-dimensional proteomics for determination of function 81
- An algorithm for genome-wide prediction of protein function 81
- Monitoring protein function by expression profiling 81
- Isotope-coded affinity tag peptide labeling 82
- Differential Proteomic Panning 82
- Cell map proteomics 83
- Topological proteomics 83
- Organelle or subcellular proteomics 84
- Nucleolar proteomics 84
- Glycoproteomic technologies 85
- High-sensitivity glycoprotein analysis 85
- Fluorescent in vivo imaging of glycoproteins 85
- Integrated approaches for protein characterization 85
- Imaging mass spectrometry 86
- IMS technologies 86
- Applications of IMS 86
- The protein microscope 87
- Automation and robotics in proteomics 87
- Western blot 88
- Limitations of WB 88
- Innovations in WB 88
- Capillary electrophoresis and WB 89
- Microfluidics and WB 89
- Multiplexing WB 89
- Applications of Western blot 89
- Research applications of Western blot 90
- Molecular diagnostic applications of Western blot 90
- Companies involved in Western blotting technologies 90
- Laser capture microdissection 91
- Microdissection techniques used for proteomics 91
- Uses of LCM in combination with proteomic technologies 92
- Concluding remarks about applications of proteomic technologies 92
- Precision proteomics 93
3. Protein biochip technology 95
- Introduction 95
- Types of protein biochips 96
- ProteinChip 96
- Applications and advantages of ProteinChip 97
- ProteinChip Biomarker System 97
- Matrix-free ProteinChip Array 98
- Aptamer-based protein biochip 98
- Fluorescence planar wave guide technology-based protein biochips 99
- Lab-on-a-chip for protein analysis 99
- Microfluidic biochips for proteomics 100
- Protein biochips for high-throughput expression 101
- Nucleic Acid-Programmable Protein Array 101
- High-density protein microarrays 101
- HPLC-Chip for protein identification 101
- Antibody microarrays 102
- Integration of protein array and image analysis 102
- Tissue microarray technology for proteomics 102
- Protein biochips in molecular diagnostics 103
- A force-based protein biochip 104
- L1 chip and lipid immobilization 104
- Multiplexed Protein Profiling on Microarrays 104
- Live cell microarrays 105
- ProteinArray Workstation 105
- Proteome arrays 106
- The Yeast ProtoArray 106
- ProtoArray™ Human Protein Microarray 106
- TRINECTIN proteome chip 107
- Peptide arrays 107
- Surface plasmon resonance technology 108
- Biacore's SPR 108
- FLEX CHIP 108
- Combination of surface plasmon resonance and MALDI-TOF 109
- Protein chips/microarrays using nanotechnology 109
- Nanoparticle protein chip 109
- Protein nanobiochip 109
- Protein nanoarrays 110
- Self-assembling protein nanoarrays 110
- Companies involved in protein biochip/microarray technology 111
4. Bioinformatics in Relation to Proteomics 115
- Introduction 115
- Bioinformatic tools for proteomics 115
- Testing of SELDI-TOF MS Proteomic Data 115
- BioImagine's ProteinMine 116
- Bioinformatics for pharmaceutical applications of proteomics 116
- In silico search of drug targets by Biopendium 116
- Compugen's LEADS 117
- DrugScore 117
- Proteochemometric modeling 117
- Integration of genomic and proteomic data 118
- Proteomic databases: creation and analysis 119
- Introduction 119
- Proteomic databases 119
- GenProtEC 120
- Human Protein Atlas 120
- Human Proteomics Initiative 121
- International Protein Index 122
- Proteome maps 122
- Protein Structure Initiative - Structural Genomics Knowledgebase 122
- Protein Warehouse Database 122
- Protein Data Bank 123
- Universal Protein Resource 123
- Protein interaction databases 123
- Biomolecular Interaction Network Database 124
- ENCODE 124
- Functional Genomics Consortium 125
- Human Proteinpedia 125
- ProteinCenter 125
- Databases of the National Center for Biotechnology Information 126
- Bioinformatics for protein identification 126
- Application of bioinformatics in functional proteomics 126
- Use of bioinformatics in protein sequencing 127
- Bottom-up protein sequencing 127
- Top-down protein sequencing 128
- Protein structural database approach to drug design 128
- Bioinformatics for high-throughput proteomics 129
- Companies with bioinformatic tools for proteomics 130
5. Research in Proteomics 131
- Introduction 131
- Applications of proteomics in biological research 131
- Identification of novel human genes by comparative proteomics 131
- Study of relationship between genes and proteins 132
- Characterization of histone codes 132
- Structural genomics or structural proteomics 133
- Protein Structure Factory 134
- Protein Structure Initiative 134
- Studies on protein structure at Argonne National Laboratory 135
- Structural Genomics Consortium 135
- Protein knockout 136
- Antisense approach and proteomics 136
- RNAi and protein knockout 136
- Total knockout of cellular proteins 136
- Ribozymes and proteomics 137
- Single molecule proteomics 137
- Single-molecule photon stamping spectroscopy 137
- Single nucleotide polymorphism determination by TOF-MS 138
- Application of proteomic technologies in systems biology 138
- Signaling pathways and proteomics 138
- Kinomics 139
- Combinatorial RNAi for quantitative protein network analysis 139
- Proteomics in neuroscience research 139
- Stem cell proteomics 140
- hESC phosphoproteome 140
- Proteomic studies of mesenchymal stem cells 141
- Proteomics of neural stem cells 141
- Proteome Biology of Stem Cells Initiative 142
- Proteomic analysis of the cell cycle 143
- Nitric oxide and proteomics 143
- A proteomic method for identification of cysteine S-nitrosylation sites
143
- Study of the nitroproteome 143
- Study of the phosphoproteome 144
- Study of the mitochondrial proteome 144
- Proteomic technologies for study of mitochondrial proteomics 145
- Cryptome 145
- Study of protein transport in health and disease 145
- Proteomics research in the academic sector 146
- Netherlands Proteins@Work 148
- ProteomeBinders initiative 148
- Rutgers University's Center for Integrative Proteomics Research 148
- Vanderbilt University's Center for Proteomics and Drug Actions 149
6. Pharmaceutical Applications of Proteomics 151
- Introduction 151
- Current drug discovery process and its limitations 151
- Role of omics in drug discovery 152
- Genomics-based drug discovery 152
- Metabolomics technologies for drug discovery 153
- Role of metabonomics in drug discovery 153
- Basis of proteomics approach to drug discovery 154
- Proteins and drug action 154
- Transcription-aided drug design 155
- Role of proteomic technologies in drug discovery 155
- Liquid chromatography-based drug discovery 156
- Capture compound mass spectrometry 157
- Protein-expression mapping by 2DGE 157
- Role of MALDI mass spectrometry in drug discovery 157
- Tissue imaging mass spectrometry 157
- Companies using MALDI for drug discovery 159
- Oxford Genome Anatomy Project 159
- Proteins as drug targets 160
- Ligands to capture the purine binding proteome 160
- Chemical probes to interrogate key protein families for drug discovery
160
- Global proteomics for pharmacodynamics 161
- CellCartaR proteomics platform 161
- ZeptoMARK™ protein profiling system 162
- Role of proteomics in targeting disease pathways 162
- Identification of protein kinases as drug targets 162
- Mechanisms of action of kinase inhibitors 163
- G-protein coupled receptors as drug targets 163
- Methods of study of GPCRs 164
- Cell-based assays for GPCR 164
- Companies involved in GPCR-based drug discovery 165
- GPCR localization database 166
- Matrix metalloproteases as drug targets 166
- PDZ proteins as drug targets 167
- Proteasome as drug target 167
- Serine hydrolases as drug targets 168
- Targeting mTOR signaling pathway 168
- Targeting caspase-8 for anticancer therapeutics 169
- Bioinformatic analysis of proteomics data for drug discovery 170
- Drug design based on structural proteomics 170
- Protein crystallography for determining 3D structure of proteins 170
- Automated 3D protein modeling 171
- Drug targeting of flexible dynamic proteins 171
- Companies involved in structure-based drug-design 171
- Integration of genomics and proteomics for drug discovery 172
- Ligand-receptor binding 173
- Role of proteomics in study of ligand-receptor binding 173
- Aptamer protein binding 174
- Systematic Evolution of Ligands by Exponential Enrichment 174
- Aptamers and high-throughput screening 174
- Nucleic Acid Biotools 175
- Aptamer beacons 175
- Peptide aptamers 176
- Riboreporters for drug discovery 176
- Target identification and validation 176
- Application of mass spectrometry for target identification 177
- Gene knockout and gene suppression for validating protein targets 177
- Laser-mediated protein knockout for target validation 177
- Integrated proteomics for drug discovery 178
- High-throughput proteomics 178
- Companies involved in high-throughput proteomics 179
- Drug discovery through protein-protein interaction studies 179
- Protein-protein interaction as basis for drug target identification 180
- Protein-PCNA interaction as basis for drug design 180
- Two-hybrid protein interaction technology for target identification 181
- Biosensors for detection of small molecule-protein interactions 181
- Protein-protein interaction maps 182
- ProNet (Myriad Genetics) 182
- Hybrigenics' maps of protein-protein interactions 182
- CellZome's functional map of protein-protein interactions 183
- Mapping of protein-protein interactions by mass spectrometry 183
- Protein interaction map of Drosophila melanogaster 184
- Protein-interaction map of Wellcome Trust Sanger Institute 184
- Protein-protein interactions as targets for therapeutic intervention 184
- Inhibition of protein-protein interactions by peptide aptamers 185
- Selective disruption of proteins by small molecules 185
- Post-genomic combinatorial biology approach 185
- Differential proteomics 186
- Shotgun proteomics 186
- Chemogenomics/chemoproteomics for drug discovery 187
- Chemoproteomics-based drug discovery 188
- Companies involved in chemogenomics/chemoproteomics 189
- Activity-based proteomics 190
- Locus Discovery technology 190
- Automated ligand identification system 191
- Expression proteomics: protein level quantification 191
- Role of phage antibody libraries in target discovery 192
- Analysis of posttranslational modification of proteins by MS 192
- Phosphoproteomics for drug discovery 193
- Application of glycoproteomics for drug discovery 193
- Role of carbohydrates in proteomics 193
- Challenges of glycoproteomics 194
- Companies involved in glycoproteomics 194
- Role of protein microarrays/ biochips for drug discovery 195
- Protein microarrays vs DNA microarrays for high-throughput screening 195
- BIA-MS biochip for protein-protein interactions 195
- ProteinChip with Surface Enhanced Neat Desorption 196
- Protein-domains microarrays 196
- Some limitations of protein biochips 196
- Concluding remarks about role of proteomics in drug discovery 197
- RNA versus protein profiling as guide to drug development 197
- RNA as drug target 197
- Combination of RNA and protein profiling 198
- RNA binding proteins 199
- Toxicoproteomics 199
- Hepatotoxicity 199
- Nephrotoxicity 200
- Cardiotoxicity 200
- Neurotoxicity 201
- Protein/peptide therapeutics 201
- Peptide-based drugs 201
- PhylomerR peptides 202
- Cryptein-based therapeutics 202
- Synthetic proteins and peptides as pharmaceuticals 203
- Genetic immunization and proteomics 203
- Proteomics and gene therapy 204
- Role of proteomics in clinical drug development 204
- Pharmacoproteomics 204
- Role of proteomics in clinical drug safety 205
7. Application of Proteomics in Human Healthcare 207
- Introduction 207
- Clinical proteomics 208
- Definition and standards 208
- Vermillion's Clinical Proteomics Program 208
- Pathophysiology of human diseases 209
- Diseases due to misfolding of proteins 209
- Mechanism of protein folding 210
- Nanoproteomics for study of misfolded proteins 211
- Therapies for protein misfolding 211
- Intermediate filament proteins 212
- Significance of mitochondrial proteome in human disease 213
- Proteome of Saccharomyces cerevisiae mitochondria 213
- Rat mitochondrial proteome 213
- Proteomic approaches to biomarker identification 214
- The ideal biomarker 214
- Proteomic technologies for biomarker discovery 214
- MALDI mass spectrometry for biomarker discovery 215
- BAMF™ Technology 215
- Protein biochips/microarrays and biomarkers 216
- Antibody-based biomarker discovery 216
- Tumor-specific serum peptidome patterns 216
- Search for protein biomarkers in body fluids 217
- Challenges and strategies for discovey of protein biomarkers in plasma
217
- 3-D structure of CD38 as a biomarker 218
- BD"! Free Flow Electrophoresis System 218
- Isotope tags for relative and absolute quantification 219
- N-terminal peptide isolation from human plasma 219
- Plasma protein microparticles as biomarkers 219
- Proteome partitioning 220
- SISCAPA method for quantitating proteins and peptides in plasma 220
- Stable isotope tagging methods 220
- Technology to measure both the identity and size of the biomarker 221
- Biomarkers in the urinary proteome 221
- Application of proteomics in molecular diagnosis 222
- Proximity ligation assay 223
- Protein patterns 223
- Proteomic tests on body fluids 223
- Cyclical amplification of proteins 225
- Applications of proteomics in infections 225
- MALDI-TOF MS for microbial identification 225
- Role of proteomics in virology 226
- Study of interaction of proteins with viruses 226
- Role of proteomics in bacteriology 227
- Epidemiology of bacterial infections 227
- Proteomic approach to bacterial pathogenesis 227
- Vaccines for bacterial infections 227
- Protein profiles associated with bacterial drug resistance 228
- Analyses of the parasite proteome 228
- Application of proteomics in cystic fibrosis 229
- Proteomics of cardiovascular diseases 229
- Pathomechanism of cardiovascular diseases 229
- Study of cardiac mitochondrial proteome in myocardial ischemia 230
- Cardiac protein databases 230
- Proteomics of dilated cardiomyopathy and heart failure 230
- Proteomic biomarkers of cardiovascular diseases 231
- Role of proteomics in cardioprotection 231
- Role of proteomics in heart transplantation 231
- Future of application of proteomics in cardiology 232
- Proteomic technologies for research in pulmonary disorders 232
- Application of proteomics in renal disorders 233
- Diagnosis of renal disorders 233
- Proteomic biomarkers of acute kidney injury 234
- Cystatin C as biomarker of glomerular filtration rate 234
- Protein biomarkers of nephritis 234
- Proteomics and kidney stones 235
- Proteomics of eye disorders 235
- Proteomics of cataract 235
- Proteomics of diabetic retinopathy 236
- Retinal dystrophies 236
- Use of proteomics in inner ear disorders 237
- Use of proteomics in aging research 237
- Removal of altered cellular proteins in aging 238
- Alteration of glycoproteins during aging 238
- Proteomics and nutrition 238
8. Oncoproteomics 239
- Introduction 239
- Proteomic technologies for study of cancer 240
- Application of CellCarta technology for oncology 240
- Accentuation of differentially expressed proteins using phage technology
240
- Identification of oncogenic tyrosine kinases using phosphoproteomics 240
- Single-cell protein expression analysis by microfluidic techniques 241
- Dynamic cell proteomics in response to a drug 241
- Desorption electrospray ionization for cancer diagnosis 241
- Proteomic analysis of cancer cell mitochondria 242
- Mass spectrometry for identification of oncogenic chimeric proteins 242
- Id proteins as targets for cancer therapy 243
- Proteomic study of p53 243
- Human Tumor Gene Index 243
- Integration of cancer genomics and proteomics 244
- Laser capture microdissection technology and cancer proteomics 244
- Cancer tissue proteomics 245
- Use of proteomics in cancers of various organ systems 245
- Proteomics of brain tumors 245
- Proteomics of breast cancer 246
- Proteomics of colorectal cancer 248
- Proteomics of esophageal cancer 248
- Proteomics of hepatic cancer 248
- Proteomics of leukemia 249
- Proteomics of lung cancer 250
- Proteomics of pancreatic cancer 250
- Proteomics of prostate cancer 250
- Diagnostic use of cancer biomarkers 251
- Proteomic technologies for tumor biomarkers 252
- Nuclear matrix proteins (NMPs) 252
- Antiannexins as tumor markers in lung cancer 253
- NCI's Network of Clinical Proteomic Technology Centers 253
- Proteomics and tumor immunology 254
- Proteomics and study of tumor invasiveness 255
- Anticancer drug discovery and development 255
- Kinase-targeted drug discovery in oncology 255
- Anticancer drug targeting: functional proteomics screen of proteases 256
- Small molecule inhibitors of cancer-related proteins 256
- Role of proteomics in studying drug resistance in cancer 257
- Future prospects of oncoproteomics 257
- Companies involved in application of proteomics to oncology 257
9. Neuroproteomics 259
- Introduction 259
- Proteomics of prion diseases 259
- Transmissible spongiform encephalopathies 260
- Creutzfeld-Jakob disease 260
- Bovine spongiform encephalopathy 261
- Variant Creutzfeldt-Jakob disease 261
- Protein misfolding and neurodegenerative disorders 261
- Ion channel link for protein-misfolding disease 261
- Detection of misfolded proteins 262
- Neurodegenerative disorders with protein abnormalities 262
- Alzheimer disease 264
- Common denominators of Alzheimer and prion diseases 264
- Parkinson disease 265
- Amyotrophic lateral sclerosis 265
- Proteomics and glutamate repeat disorders 266
- Proteomics and Huntington's disease 266
- Proteomics and demyelinating diseases 267
- Proteomics of neurogenetic disorders 267
- Fabry disease 267
- GM1 gangliosidosis 268
- Quantitative proteomics and familial hemiplegic migraine 268
- Proteomics of spinal muscular atrophy 269
- Proteomics of CNS trauma 269
- Proteomics of traumatic brain injury 269
- Chronic traumatic encephalopathy and ALS 270
- Proteomics of CNS aging 270
- Protein aggregation as a bimarker of aging 270
- Neuroproteomics of psychiatric disorders 271
- Neuroproteomic of cocaine addiction 271
- Neurodiagnostics based on proteomics 272
- Disease-specific proteins in the cerebrospinal fluid 272
- Tau proteins 273
- CNS tissue proteomics 273
- Diagnosis of CNS disorders by examination of proteins in urine 275
- Diagnosis of CNS disorders by examination of proteins in the blood 275
- Serum pNF-H as biomarker of CNS damage 276
- Proteomics of BBB 276
- Future prospects of neuroproteomics in neurology 277
- HUPO's Pilot Brain Proteome Project 278
10. Commercial Aspects of Proteomics 279
- Introduction 279
- Potential markets for proteomic technologies 279
- Bioinformatics markets for proteomics 280
- Markets for protein separation technologies 280
- Markets for 2D gel electrophoresis 280
- Market trends in protein separation technolgies 281
- Protein purification markets 281
- Mass spectrometry markets 281
- Markets for MALDI for drug discovery 282
- Markets for nuclear magnetic resonance spectroscopy 282
- Market for structure-based drug design 282
- Markets for protein biomarkers 283
- Markets for cell-based protein assays 283
- Protein biochip markets 283
- Western blot markets 283
- Geographical distribution of proteomics technologies markets 284
- Business and strategic considerations 284
- Cost of protein structure determination 284
- Opinion surveys of the scientist consumers of proteomic technologies 284
- Opinions on mass spectrometry 284
- Opinions on bioinformatics and proteomic databases 285
- Systems for in vivo study of protein-protein interactions 285
- Perceptions of the value of protein biochip/microfluidic systems 285
- Small versus big companies 285
- Expansion in proteomics according to area of application 286
- Growth trends in cell-based protein assay market 286
- Challenges for development of cell-based protein assays 286
- Future trends and prospects of cell-based protein assays 287
- Strategic collaborations 287
- Analysis of proteomics collaborations according to types of companies
287
- Types of proteomic collaborations 288
- Proteomics collaborations according to application areas 288
- Analysis of proteomics collaborations: types of technologies 289
- Collaborations based on protein biochip technology 289
- Concluding remarks about proteomic collaborations 290
- Proteomic patents 290
- Market drivers in proteomics 291
- Needs of the pharmaceutical industry 291
- Need for outsourcing proteomic technologies 291
- Funding of proteomic companies and research 291
- Technical advances in proteomics 292
- Changing trends in healthcare in future 292
- Challenges facing proteomics 292
- Magnitude and complexity of the task 292
- Technical challenges 293
- Limitations of proteomics 293
- Limitations of 2DGE 293
- Limitations of mass spectrometry techniques 293
- Complexity of the pharmaceutical proteomics 294
- Unmet needs in proteomics 294
11. Future of Proteomics 297
- Genomics to proteomics 297
- Faster technologies 297
- FLEXGene repository 297
- Need for new proteomic technologies 298
- Emerging proteomic technologies 299
- Detection of alternative protein isoforms 299
- Direct protein identification in large genomes by mass spectrometry 299
- Proteome identification kits with stacked membranes 299
- Vacuum deposition interface 300
- In vitro protein biosynthesis 300
- Proteome mining with adenosine triphosphate 300
- Proteome-scale purification of human proteins from bacteria 300
- Proteostasis network 301
- Cytoproteomics 301
- Subcellular proteomics 301
- Individual cell proteomics 302
- Live cell proteomics 302
- Fluorescent proteins for live-cell imaging 303
- Membrane proteomics 303
- Identification of membrane proteins by tandem MS of protein ions 303
- Solid state NMR for study of nanocrystalline membrane proteins 304
- Multiplex proteomics 304
- High-throughput for proteomics 304
- Future directions for protein biochip application 305
- Bioinformatics for proteomics 305
- High-Throughput Crystallography Consortium 305
- Study of protein folding by IBM's Blue Gene 306
- Study of proteins by atomic force microscopy 306
- Population proteomics 306
- Comparative proteome analysis 307
- Human Proteome Organization 307
- Human Salivary Proteome 308
- Academic-commercial collaborations in proteomics 308
- Indiana Centers for Applied Protein Sciences 308
- Role of proteomics in the healthcare of the future 309
- Proteomics and molecular medicine 309
- Proteodiagnostics 309
- Proteomics and personalized medicine 310
- Targeting the ubiquitin pathway for personalized therapy of cancer 310
- Protein patterns and personalized medicine 310
- Personalizing interferon therapy of hepatitis C virus 312
- Protein biochips and personalized medicine 312
- Combination of diagnostics and therapeutics 313
- Future prospects 313
12. References 315
Tables
- Table 1-1: Landmarks in the evolution of proteomics 19
- Table 1-2: Comparison of DNA and protein 28
- Table 1-3: Comparison of mRNA and protein 28
- Table 1-4: Methods of analysis at various levels of functional genomics
34
- Table 2-1: Proteomics technologies 37
- Table 2-2: Protein separation technologies of selected companies 42
- Table 2-3: Companies supplying mass spectrometry instruments 45
- Table 2-4: Companies involved in cell-based protein assays 67
- Table 2-5: Methods used for the study of protein-protein interactions 69
- Table 2-6: A selection of companies involved in protein-protein
interaction studies 75
- Table 2-7: Companies involved in Western blotting 90
- Table 2-8: Proteomic technologies used with laser capture microdissection
92
- Table 3-1: Applications of protein biochip technology 95
- Table 3-2: Selected companies involved in protein biochip/microarray
technology 111
- Table 4-1: Proteomic databases and other Internet sources of proteomics
information 119
- Table 4-2: Protein interaction databases available on the Internet 124
- Table 4-3: Bioinformatic tools for proteomics from academic sources
129
- Table 4-4: Selected companies involved in bioinformatics for proteomics
130
- Table 5-1: Applications of proteomics in basic biological research 131
- Table 5-2: A sampling of proteomics research projects in academic
institutions 146
- Table 6-1: Pharmaceutical applications of proteomics 151
- Table 6-2: Selected companies relevant to MALDI-MS for drug discovery
159
- Table 6-3: Selected companies involved in GPCR-based drug discovery 165
- Table 6-4: Companies involved in drug design based on structural
proteomics 172
- Table 6-5: Proteomic companies with high-throughput protein expression
technologies 179
- Table 6-6: Selected companies involved in chemogenomics/chemoproteomics
189
- Table 6-7: Companies involved in glycoproteomic technologies 194
- Table 7-1: Applications of proteomics in human healthcare 207
- Table 7-2: Eye disorders and proteomic approaches 235
- Table 8-1: Companies involved in applications of proteomics to oncology
258
- Table 9-1: Neurodegenerative diseases with underlying protein abnormality
262
- Table 9-2: Disease-specific proteins in the cerebrospinal fluid of
patients 272
- Table 10-1: Potential markets for proteomic technologies 2011-2021 279
- Table 10-2: 2011 revenues of major companies from protein separation
technologies 280
- Table 10-3: Geographical distribution of markets for proteomic
technologies 2011-2021 284
- Table 11-1: Role of proteomics in personalizing strategies for cancer
therapy 310
Figures
- Figure 1-1: A schematic miRNA pathway 22
- Figure 1-2: Relationship of DNA, RNA and protein in the cell 29
- Figure 1-3: Protein production pathway from gene expression to functional
protein with controls. 31
- Figure 1-4: Parallels between functional genomics and proteomics 32
- Figure 2-1: Proteomics: flow from sample preparation to characterization
38
- Figure 2-2: The central role of spectrometry in proteomics 45
- Figure 2-3: Electrospray ionization (ESI) 46
- Figure 2-4: Matrix-Assisted Laser Desorption/Ionization (MALDI) 47
- Figure 2-5: Scheme of bio-bar-code assay 62
- Figure 2-6: A diagrammatic presentation of yeast two-hybrid system 70
- Figure 3-1: ProteinChip System 97
- Figure 3-2: Surface plasma resonance (SPR) 108
- Figure 4-1: Role of bioinformatics in integrating genomic/proteomic-based
drug discovery 118
- Figure 4-2: Bottom-up and top-down approaches for protein sequencing
127
- Figure 6-1: Drug discovery process 152
- Figure 6-2: Regulatory changes induced by drugs and implemented at the
proteins level. 155
- Figure 6-3: Relation of proteome to genome, diseases and drugs 156
- Figure 6-4: The mTOR pathways 169
- Figure 6-5: Steps in shotgun proteomics 187
- Figure 6-6: Chemogenomic approach to drug discovery (3-Dimensional
Pharmaceuticals) 188
- Figure 8-1: Relation of oncoproteomics to other technologies 239
- Figure 9-1: A scheme of proteomics applications in CNS drug discovery and
development 278
- Figure 10-1: Types of companies involved in proteomics collaborations
288
- Figure 10-2: Types of collaborations: R & D, licensing or marketing 288
- Figure 10-3: Proteomics collaborations according to application areas
289
- Figure 10-4: Proteomics collaborations according to technologies 289
- Figure 10-5: Unmet needs in proteomics 295
- Figure 11-1: A scheme of the role of proteomics in personalized management
of cancer 312
Part II
11. Companies involved in developing proteomics 4
- Introduction 4
- Profiles of selected companies 10
- Collaborations 249
Tables
- Table 11-1: Companies with proteomics as the main activity/service 4
- Table 11-2: Selected companies with equipment and laboratory services for
proteomics 6
- Table 11-3: Biotechnology and drug discovery companies involved in
proteomics 6
- Table 11-4: Bioinformatics companies involved in proteomics 8
- Table 11-5: Biopharmaeutical companies with in-house proteomics technology
9
- Table 11-6: Major players in proteomics 9
- Table 10-7: Selected collaborations of companies in the area of proteomics
249
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