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Proteomics - Technologies, Markets and Companies

Notes

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.

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 44 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 223 of these are profiled in the report with 460 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 2013 and are projected to years 2018 and 2023. 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 22
  • Decoding of mRNA by the ribosome 23
  • Genes 23
  • Alternative splicing 23
  • Transcription 24
  • Gene regulation 25
  • Gene expression 25
  • Chromatin 26
  • Golgi complex 26
  • Proteins 27
  • Spliceosome 27
  • Functions of proteins 27
  • Inter-relationship of protein, mRNA and DNA 28
  • Proteomics 29
  • Mitochondrial proteome 31
  • S-nitrosoproteins in mitochondria 31
  • Proteomics and genomics 31
  • Classification of proteomics 34
  • Levels of functional genomics and various "omics" 34
  • Glycoproteomics 34
  • Transcriptomics 35
  • Metabolomics 35
  • Cytomics 35
  • Phenomics 35
  • Impact of the genetic factors on the human proteome 36
  • Proteomics and systems biology 36
  • Functional synthetic proteins 37

2. Proteomic Technologies 39

  • Key technologies driving proteomics 39
  • Sample preparation 40
  • New trends in sample preparation 40
  • Pressure Cycling Technology 41
  • Protein separation technologies 41
  • High resolution 2DGE 41
  • Variations of 2D gel technology 42
  • Limitations of 2DGE and measures to overcome these 42
  • 1-D sodium dodecyl sulfate (SDS) PAGE 42
  • Capillary electrophoresis systems 43
  • Head column stacking capillary zone electrophoresis 43
  • Removal of albumin and IgG 43
  • SeraFILE™ separations platform 44
  • Companies with protein separation technologies 44
  • Protein purification 46
  • Technologies for protein purification 46
  • Applications of protein purification 46
  • Protein detection 46
  • Protein identification and characterization 47
  • Mass spectrometry (MS) 47
  • Electrospray ionization 47
  • Desorption electrospray ionization MS 49
  • Mirosaic 3500 MiD 49
  • Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 49
  • Cryogenic MALDI- Fourier Transform Mass Spectrometry 51
  • Stable-isotope-dilution tandem mass spectrometry 51
  • HUPO Gold MS Protein Standard 51
  • Companies involved in mass spectrometry 52
  • High performance liquid chromatography 52
  • Multidimensional protein identification technology (MudPIT) 53
  • Multiple reaction monitoring assays 53
  • Peptide mass fingerprinting 54
  • Combination of protein separation technologies with mass spectrometry 54
  • Combining capillary electrophoresis with mass spectrometry 54
  • 2D PAGE and mass spectrometry 54
  • Quantification of low abundance proteins 55
  • SDS-PAGE 55
  • Antibodies and proteomics 55
  • Detection of fusion proteins 56
  • Labeling and detection of proteins 56
  • Fluorescent labeling of proteins in living cells 57
  • Combination of microspheres with fluorescence 57
  • Self-labeling protein tags 57
  • Analysis of peptides 57
  • C-terminal peptide analysis 58
  • Differential Peptide Display 59
  • Peptide analyses using NanoLC-MS 59
  • Protein sequencing 60
  • Real-time PCR for protein quantification 61
  • Quantitative proteomics 61
  • MS-based quantitative proteomics 61
  • MS and cryo-electron tomography 61
  • Selected reaction monitoring MS 62
  • Functional proteomics: technologies for studying protein function 62
  • Functional genomics by mass spectrometry 62
  • LC-MS-based method for annotating the protein-coding genome 62
  • RNA-Protein fusions 63
  • Designed repeat proteins 63
  • Application of nanobiotechnology to proteomics 64
  • Nanoproteomics 64
  • Nanoflow liquid chromatography 64
  • Nanopores for phosphoprotein analysis 65
  • Nanotube electronic biosensor for proteomics 65
  • Protein nanocrystallography 65
  • Single-molecule mass spectrometry using a nanopore 65
  • Nanoelectrospray ionization 66
  • Nanoproteomics for discovery of protein biomarkers in the blood 66
  • QD-protein nanoassembly 66
  • Nanoparticle barcodes 67
  • Biobarcode assay for proteins 67
  • Nanopore-based protein sequencing 68
  • Nanoscale protein analysis 68
  • Nanoscale mechanism for protein engineering 69
  • Nanotube electronic biosensor 69
  • Nanotube-vesicle networks for study of membrane proteins 70
  • Nanowire transistor for the detection of protein-protein interactions 70
  • Qdot-nanocrystals 70
  • Resonance Light Scattering technology 71
  • Study of single membrane proteins at subnanometer resolution 71
  • Protein expression profiling 71
  • Cell-based protein assays 72
  • Living cell-based assays for protein function 73
  • Companies developing cell-based protein assays 73
  • Protein function studies 74
  • Transcriptionally Active PCR 74
  • Protein-protein interactions 74
  • Bacterial protein interaction studies for assigning function 76
  • Bioluminescence Resonance Energy Transfer 76
  • Computational prediction of interactions 76
  • Detection Enhanced Ubiquitin Split Protein Sensor technology 77
  • Double Switch technology 77
  • Fluorescence Resonance Energy Transfer 77
  • In vivo study of protein-protein interactions 78
  • In vitro study of protein-protein interactions 78
  • Interactome 78
  • Membrane 1-hybrid method 79
  • Phage display 80
  • Protein affinity chromatography 80
  • Protein-fragment complementation system 80
  • Yeast 2-hybrid system 80
  • Companies with technologies for protein-protein interaction studies 81
  • Protein-DNA interaction 82
  • Determination of protein structure 83
  • X-Ray crystallography 83
  • Nuclear magnetic resonance 84
  • Electron spin resonance 84
  • Prediction of protein structure 85
  • Protein tomography 85
  • X-ray scattering-based method for determining the structure of proteins 86
  • Prediction of protein function 86
  • Three-dimensional proteomics for determination of function 87
  • An algorithm for genome-wide prediction of protein function 87
  • Monitoring protein function by expression profiling 87
  • Isotope-coded affinity tag peptide labeling 88
  • Differential Proteomic Panning 88
  • Cell map proteomics 89
  • Topological proteomics 89
  • Organelle or subcellular proteomics 90
  • Nucleolar proteomics 90
  • Glycoproteomic technologies 91
  • High-sensitivity glycoprotein analysis 91
  • Fluorescent in vivo imaging of glycoproteins 91
  • Integrated approaches for protein characterization 91
  • Imaging mass spectrometry 92
  • IMS technologies 92
  • Applications of IMS 93
  • The protein microscope 93
  • Tag-Mass IMS 93
  • Automation and robotics in proteomics 94
  • Western blot 94
  • Limitations of WB 94
  • Innovations in WB 95
  • Capillary electrophoresis and WB 95
  • Chemiluminescent western blotting 95
  • Fluorescent WB 96
  • Microfluidics and WB 96
  • Multiplexing WB 97
  • Applications of Western blot 97
  • Research applications of Western blot 97
  • Molecular diagnostic applications of Western blot 97
  • Companies involved in Western blotting technologies 98
  • Laser capture microdissection 99
  • Microdissection techniques used for proteomics 99
  • Uses of LCM in combination with proteomic technologies 99
  • Concluding remarks about applications of proteomic technologies 100
  • Precision proteomics 101

3. Protein biochip technology 103

  • Introduction 103
  • Types of protein biochips 104
  • ProteinChip 104
  • Applications and advantages of ProteinChip 105
  • ProteinChip Biomarker System 105
  • Matrix-free ProteinChip Array 106
  • Aptamer-based protein biochip 106
  • Fluorescence planar wave guide technology-based protein biochips 107
  • Lab-on-a-chip for protein analysis 107
  • Biochips for peptide arrays 108
  • Microfluidic biochips for proteomics 108
  • Protein biochips for high-throughput expression 109
  • Nucleic Acid-Programmable Protein Array 109
  • High-density protein microarrays 109
  • HPLC-Chip for protein identification 110
  • Antibody microarrays 110
  • Integration of protein array and image analysis 110
  • Tissue microarray technology for proteomics 111
  • Protein biochips in molecular diagnostics 111
  • A force-based protein biochip 112
  • L1 chip and lipid immobilization 112
  • Multiplexed Protein Profiling on Microarrays 112
  • Live cell microarrays 113
  • ProteinArray Workstation 113
  • Proteome arrays 114
  • The Yeast ProtoArray 114
  • ProtoArray™ Human Protein Microarray 114
  • TRINECTIN proteome chip 115
  • Peptide arrays 115
  • Surface plasmon resonance technology 116
  • Biacore's SPR 116
  • FLEX CHIP 116
  • Combination of surface plasmon resonance and MALDI-TOF 117
  • Protein chips/microarrays using nanotechnology 117
  • Nanoparticle protein chip 117
  • Protein nanobiochip 118
  • Protein nanoarrays 118
  • Self-assembling protein nanoarrays 118
  • Companies involved in protein biochip/microarray technology 119

4. Bioinformatics in Relation to Proteomics 123

  • Introduction 123
  • Bioinformatic tools for proteomics 123
  • Testing of SELDI-TOF MS Proteomic Data 123
  • BioImagine's ProteinMine 124
  • Bioinformatics for pharmaceutical applications of proteomics 124
  • In silico search of drug targets by Biopendium 124
  • Compugen's LEADS 125
  • DrugScore 125
  • Proteochemometric modeling 125
  • Integration of genomic and proteomic data 126
  • Proteomic databases: creation and analysis 127
  • Introduction 127
  • Proteomic databases 127
  • GenProtEC 128
  • Human Protein Atlas 128
  • Human Proteomics Initiative 129
  • Human proteome map 130
  • International Protein Index 130
  • MS-based draft of the human proteome 130
  • Protein Structure Initiative - Structural Genomics Knowledgebase 130
  • Protein Warehouse Database 131
  • Protein Data Bank 131
  • Repository for raw data from proteomics MS 131
  • Universal Protein Resource 132
  • Protein interaction databases 132
  • Biomolecular Interaction Network Database 133
  • ENCODE 133
  • Functional Genomics Consortium 134
  • Human Proteinpedia 134
  • ProteinCenter 134
  • Databases of the National Center for Biotechnology Information 135
  • Application of bioinformatics for protein identification 135
  • Tandem MS for protein identification 135
  • Targeted MS for specific identification of proteins 135
  • Application of bioinformatics in functional proteomics 136
  • Use of bioinformatics in protein sequencing 136
  • Bottom-up protein sequencing 137
  • Top-down protein sequencing 138
  • Protein structural database approach to drug design 138
  • Bioinformatics for high-throughput proteomics 138
  • Bioinformatics for protein-protein interactions 139
  • Companies with bioinformatic tools for proteomics 140

5. Research in Proteomics 143

  • Introduction 143
  • Applications of proteomics in biological research 143
  • Identification of novel human genes by comparative proteomics 143
  • Study of relationship between genes and proteins 144
  • Characterization of histone codes 144
  • Structural genomics or structural proteomics 145
  • Protein Structure Factory 146
  • Protein Structure Initiative 146
  • Studies on protein structure at Argonne National Laboratory 147
  • Structural Genomics Consortium 147
  • Protein knockout 148
  • Antisense approach and proteomics 148
  • RNAi and protein knockout 148
  • Total knockout of cellular proteins 149
  • Ribozymes and proteomics 149
  • Single molecule proteomics 149
  • Single-molecule photon stamping spectroscopy 149
  • Single nucleotide polymorphism determination by TOF-MS 150
  • Application of proteomic technologies in systems biology 150
  • Signaling pathways and proteomics 151
  • Kinomics 151
  • Combinatorial RNAi for quantitative protein network analysis 151
  • Proteomics in neuroscience research 152
  • Stem cell proteomics 152
  • Comparative proteomic analysis of somatic cells, iPSCs and ESCs 153
  • hESC phosphoproteome 153
  • Proteomic studies of mesenchymal stem cells 153
  • Proteomics of neural stem cells 154
  • Proteome Biology of Stem Cells Initiative 154
  • Proteomic analysis of the cell cycle 155
  • Nitric oxide and proteomics 155
  • A proteomic method for identification of cysteine S-nitrosylation sites 155
  • Study of the nitroproteome 156
  • Study of the phosphoproteome 156
  • Study of the mitochondrial proteome 157
  • Proteomic technologies for study of mitochondrial proteomics 157
  • Cryptome 158
  • Study of protein transport in health and disease 158
  • Ancient proteomics 158
  • Proteomics research in the academic sector 159
  • Netherlands Proteins@Work 161
  • ProteomeBinders initiative 161
  • Rutgers University's Center for Integrative Proteomics Research 161
  • Vanderbilt University's Center for Proteomics and Drug Actions 162

6. Pharmaceutical Applications of Proteomics 163

  • Introduction 163
  • Current drug discovery process and its limitations 163
  • Role of omics in drug discovery 164
  • Genomics-based drug discovery 164
  • Metabolomics technologies for drug discovery 165
  • Role of metabonomics in drug discovery 165
  • Basis of proteomics approach to drug discovery 166
  • Proteins and drug action 166
  • Transcription-aided drug design 167
  • Role of proteomic technologies in drug discovery 167
  • Liquid chromatography-based drug discovery 168
  • Capture compound mass spectrometry 169
  • Protein-expression mapping by 2DGE 169
  • Protein-protein interactions and drug discovery 169
  • Role of MALDI mass spectrometry in drug discovery 169
  • Structural proteomics and drug discovery 170
  • Tissue imaging mass spectrometry 171
  • Oxford Genome Anatomy Project 172
  • Proteins as drug targets 172
  • Ligands to capture the purine binding proteome 173
  • Chemical probes to interrogate key protein families for drug discovery 173
  • Global proteomics for pharmacodynamics 174
  • CellCarta® proteomics platform 174
  • ZeptoMARK™ protein profiling system 175
  • Role of proteomics in targeting disease pathways 175
  • Dynamic proteomics 175
  • Identification of protein kinases as drug targets 176
  • Mechanisms of action of kinase inhibitors 176
  • G-protein coupled receptors as drug targets 177
  • Methods of study of GPCRs 177
  • Cell-based assays for GPCR 177
  • Companies involved in GPCR-based drug discovery 178
  • GPCR localization database 179
  • Matrix metalloproteases as drug targets 179
  • PDZ proteins as drug targets 180
  • Proteasome as drug target 180
  • Serine hydrolases as drug targets 181
  • Targeting mTOR signaling pathway 181
  • Targeting caspase-8 for anticancer therapeutics 182
  • Bioinformatic analysis of proteomics data for drug discovery 183
  • Drug design based on structural proteomics 183
  • Protein crystallography for determining 3D structure of proteins 183
  • Automated 3D protein modeling 184
  • Drug targeting of flexible dynamic proteins 184
  • Companies involved in structure-based drug-design 184
  • Integration of genomics and proteomics for drug discovery 185
  • Ligand-receptor binding 186
  • Role of proteomics in study of ligand-receptor binding 186
  • Measuring drug binding of proteins 187
  • Aptamer protein binding 187
  • Systematic Evolution of Ligands by Exponential Enrichment 187
  • Aptamers and high-throughput screening 188
  • Nucleic Acid Biotools 188
  • Aptamer beacons 189
  • Peptide aptamers 189
  • Riboreporters for drug discovery 189
  • Target identification and validation 190
  • Application of mass spectrometry for target identification 190
  • Gene knockout and gene suppression for validating protein targets 190
  • Laser-mediated protein knockout for target validation 191
  • Integrated proteomics for drug discovery 191
  • High-throughput proteomics 192
  • Companies involved in high-throughput proteomics 192
  • Drug discovery through protein-protein interaction studies 193
  • Protein-protein interaction as basis for drug target identification 193
  • Protein-PCNA interaction as basis for drug design 194
  • Two-hybrid protein interaction technology for target identification 194
  • Biosensors for detection of small molecule-protein interactions 195
  • Protein-protein interaction maps 195
  • ProNet (Myriad Genetics) 195
  • Hybrigenics' maps of protein-protein interactions 196
  • CellZome's functional map of protein-protein interactions 196
  • Mapping of protein-protein interactions by mass spectrometry 197
  • Protein interaction map of Drosophila melanogaster 197
  • Protein-interaction map of Wellcome Trust Sanger Institute 197
  • Protein-protein interactions as targets for therapeutic intervention 198
  • Inhibition of protein-protein interactions by peptide aptamers 198
  • Selective disruption of proteins by small molecules 198
  • Post-genomic combinatorial biology approach 199
  • Differential proteomics 199
  • Shotgun proteomics 200
  • Chemogenomics/chemoproteomics for drug discovery 200
  • Chemoproteomics-based drug discovery 201
  • Companies involved in chemogenomics/chemoproteomics 202
  • Activity-based proteomics 203
  • Locus Discovery technology 203
  • Automated ligand identification system 204
  • Expression proteomics: protein level quantification 205
  • Role of phage antibody libraries in target discovery 205
  • Analysis of posttranslational modification of proteins by MS 205
  • Phosphoproteomics for drug discovery 206
  • Application of glycoproteomics for drug discovery 206
  • Role of carbohydrates in proteomics 206
  • Challenges of glycoproteomics 207
  • Companies involved in glycoproteomics 207
  • Role of protein microarrays/ biochips for drug discovery 208
  • Protein microarrays vs DNA microarrays for high-throughput screening 208
  • BIA-MS biochip for protein-protein interactions 209
  • ProteinChip with Surface Enhanced Neat Desorption 209
  • Protein-domains microarrays 209
  • Some limitations of protein biochips 210
  • Concluding remarks about role of proteomics in drug discovery 210
  • RNA versus protein profiling as guide to drug development 211
  • RNA as drug target 211
  • Combination of RNA and protein profiling 212
  • RNA binding proteins 212
  • Toxicoproteomics 212
  • Hepatotoxicity 212
  • Nephrotoxicity 213
  • Cardiotoxicity 214
  • Neurotoxicity 214
  • Protein/peptide therapeutics 214
  • Alphabody technology for improving protein therapeutics 214
  • Peptide-based drugs 215
  • Phylomer® peptides 215
  • Cryptein-based therapeutics 215
  • Synthetic proteins and peptides as pharmaceuticals 216
  • Genetic immunization and proteomics 217
  • Proteomics and gene therapy 217
  • Role of proteomics in clinical drug development 218
  • Pharmacoproteomics 218
  • Role of proteomics in clinical drug safety 218

7. Application of Proteomics in Human Healthcare 221

  • Introduction 221
  • Clinical proteomics 222
  • Definition and standards 222
  • Vermillion's Clinical Proteomics Program 222
  • Pathophysiology of human diseases 223
  • Diseases due to misfolding of proteins 223
  • Mechanism of protein folding 224
  • Nanoproteomics for study of misfolded proteins 225
  • Therapies for protein misfolding 225
  • Intermediate filament proteins 226
  • Significance of mitochondrial proteome in human disease 227
  • Proteome of Saccharomyces cerevisiae mitochondria 227
  • Rat mitochondrial proteome 227
  • Proteomic approaches to biomarker identification 228
  • The ideal biomarker 228
  • Proteomic technologies for biomarker discovery 228
  • MALDI mass spectrometry for biomarker discovery 229
  • BAMF™ Technology 229
  • Protein biochips/microarrays and biomarkers 230
  • Affinity proteomics for discovery of biomarkers 230
  • Antibody array-based biomarker discovery 230
  • Discovery of biomarkers by MAb microarray profiling 231
  • Tumor-specific serum peptidome patterns 231
  • Search for protein biomarkers in body fluids 232
  • Challenges and strategies for discovey of protein biomarkers in plasma 232
  • 3-D structure of CD38 as a biomarker 233
  • BD™ Free Flow Electrophoresis System 233
  • Isotope tags for relative and absolute quantification 233
  • N-terminal peptide isolation from human plasma 234
  • Plasma protein microparticles as biomarkers 234
  • Proteome partitioning 235
  • SISCAPA method for quantitating proteins and peptides in plasma 235
  • Stable isotope tagging methods 235
  • Technology to measure both the identity and size of the biomarker 236
  • Biomarkers in the urinary proteome 236
  • Application of proteomics in molecular diagnosis 237
  • MassARRAY 237
  • Proximity ligation assay 238
  • Protein patterns 238
  • Proteomic tests on body fluids 239
  • Cyclical amplification of proteins 240
  • Applications of proteomics in infections 240
  • MALDI-TOF MS for microbial identification 241
  • Role of proteomics in virology 241
  • Interaction of proteins with viruses 242
  • Quantitative temporal viromics 242
  • Role of proteomics in bacteriology 242
  • Epidemiology of bacterial infections 243
  • Proteomic approach to bacterial pathogenesis 243
  • Vaccines for bacterial infections 243
  • Protein profiles associated with bacterial drug resistance 244
  • Analyses of the parasite proteome 244
  • Application of proteomics in cystic fibrosis 244
  • Proteomics of cardiovascular diseases 245
  • Pathomechanism of cardiovascular diseases 245
  • Protein misfolding in cardiac dysfunction 245
  • Study of cardiac mitochondrial proteome in myocardial ischemia 246
  • Cardiac protein databases 246
  • Proteomics of dilated cardiomyopathy and heart failure 246
  • Proteomic biomarkers of cardiovascular diseases 247
  • Role of proteomics in cardioprotection 247
  • Role of proteomics in heart transplantation 248
  • Future of application of proteomics in cardiology 248
  • Proteomic technologies for research in pulmonary disorders 248
  • Application of proteomics in renal disorders 250
  • Diagnosis of renal disorders 250
  • Proteomic biomarkers of acute kidney injury 250
  • Cystatin C as biomarker of glomerular filtration rate 250
  • Protein biomarkers of nephritis 251
  • Proteomics and kidney stones 251
  • Proteomics of eye disorders 251
  • Proteomics of cataract 252
  • Proteomics of diabetic retinopathy 252
  • Retinal dystrophies 253
  • Use of proteomics in inner ear disorders 253
  • Use of proteomics in aging research 253
  • Alteration of glycoproteins during aging 254
  • Removal of altered cellular proteins in aging 254
  • Study of the role of Parkin in modulating aging 254
  • Proteomics and nutrition 255

8. Oncoproteomics 257

  • Introduction 257
  • Proteomic technologies for study of cancer 258
  • Application of CellCarta technology for oncology 258
  • Accentuation of differentially expressed proteins using phage technology 258
  • Cancer tissue proteomics 258
  • Dynamic cell proteomics in response to a drug 259
  • Desorption electrospray ionization for cancer diagnosis 259
  • Id proteins as targets for cancer therapy 260
  • Identification of oncogenic tyrosine kinases using phosphoproteomics 260
  • Laser capture microdissection technology and cancer proteomics 260
  • Mass spectrometry for identification of oncogenic chimeric proteins 261
  • Proteomic analysis of cancer cell mitochondria 261
  • Proteomic study of p53 262
  • Human Tumor Gene Index 262
  • Integration of cancer genomics and proteomics 262
  • Role of proteomics in study of cancer stem cell biology 263
  • Single-cell protein expression analysis by microfluidic techniques 263
  • Use of proteomics in cancers of various organ systems 263
  • Proteomics of brain tumors 263
  • Malignant glial tumors 263
  • Meningiomas 264
  • DESI-MS for intraoperative diagnosis of brain tumors 264
  • Proteomics of breast cancer 265
  • Integration of proteomic and genomic data for breast cancer 266
  • Proteomics of colorectal cancer 267
  • Proteomics of esophageal cancer 267
  • Proteomics of hepatic cancer 268
  • Proteomics of leukemia 268
  • Proteomics of lung cancer 269
  • Proteomics of pancreatic cancer 270
  • Proteomics of prostate cancer 270
  • Proteomics of renal cancer 271
  • Diagnostic use of cancer biomarkers 271
  • Proteomic technologies for tumor biomarkers 272
  • Nuclear matrix proteins (NMPs) 272
  • Antiannexins as tumor markers in lung cancer 273
  • NCI's Network of Clinical Proteomic Technology Centers 273
  • Proteomics and tumor immunology 274
  • Proteomics and study of tumor invasiveness 275
  • Anticancer drug discovery and development 275
  • Kinase-targeted drug discovery in oncology 275
  • Anticancer drug targeting: functional proteomics screen of proteases 276
  • Small molecule inhibitors of cancer-related proteins 276
  • Role of proteomics in studying drug resistance in cancer 276
  • Future prospects of oncoproteomics 277
  • Clinical Proteomic Tumor Analysis Consortium 277
  • Companies involved in application of proteomics to oncology 278

9. Neuroproteomics 281

  • Introduction 281
  • Application of proteomics for the study of nervous system 281
  • Proteomics of prion diseases 282
  • Normal function of prions in the brain 282
  • Diseases due to pathological prion protein 282
  • Transmissible spongiform encephalopathies 283
  • Creutzfeld-Jakob disease 283
  • Bovine spongiform encephalopathy 283
  • Variant Creutzfeldt-Jakob disease 284
  • Protein misfolding and neurodegenerative disorders 284
  • Ion channel link for protein-misfolding disease 284
  • Detection of misfolded proteins 284
  • Neurodegenerative disorders with protein abnormalities 285
  • Alzheimer disease 287
  • Common denominators of Alzheimer and prion diseases 287
  • Parkinson disease 288
  • Amyotrophic lateral sclerosis 288
  • Proteomics and glutamate repeat disorders 289
  • Proteomics and Huntington's disease 289
  • Proteomics and demyelinating diseases 290
  • Proteomics of neurogenetic disorders 290
  • Fabry disease 290
  • GM1 gangliosidosis 291
  • Quantitative proteomics and familial hemiplegic migraine 291
  • Proteomics of spinal muscular atrophy 292
  • Proteomics of CNS trauma 292
  • Proteomics of traumatic brain injury 292
  • Chronic traumatic encephalopathy and ALS 293
  • Proteomics of cerebrovascular disease 293
  • Proteomics of CNS aging 294
  • Protein aggregation as a bimarker of aging 294
  • Neuroproteomics of psychiatric disorders 295
  • Neuroproteomic of cocaine addiction 295
  • Neurodiagnostics based on proteomics 296
  • Disease-specific proteins in the cerebrospinal fluid 296
  • Tau proteins 297
  • CNS tissue proteomics 297
  • Diagnosis of CNS disorders by examination of proteins in urine 299
  • Diagnosis of CNS disorders by examination of proteins in the blood 299
  • Serum pNF-H as biomarker of CNS damage 300
  • Proteomics of BBB 300
  • Future prospects of neuroproteomics in neurology 300
  • HUPO's Pilot Brain Proteome Project 302

10. Proteomics Markets 303

  • Introduction 303
  • Potential markets for proteomic technologies 303
  • Bioinformatics markets for proteomics 304
  • Markets for protein separation technologies 304
  • Markets for 2D gel electrophoresis 304
  • Market trends in protein separation technolgies 305
  • Protein purification markets 305
  • Mass spectrometry markets 305
  • Markets for MALDI for drug discovery 306
  • Markets for nuclear magnetic resonance spectroscopy 306
  • Market for structure-based drug design 306
  • Markets for protein biomarkers 307
  • Markets for cell-based protein assays 307
  • Protein biochip markets 307
  • Western blot markets 307
  • Geographical distribution of proteomics technologies markets 308
  • Business and strategic considerations 308
  • Cost of protein structure determination 308
  • Opinion surveys of the scientist consumers of proteomic technologies 308
  • Opinions on mass spectrometry 308
  • Opinions on bioinformatics and proteomic databases 309
  • Systems for in vivo study of protein-protein interactions 309
  • Perceptions of the value of protein biochip/microfluidic systems 309
  • Small versus big companies 309
  • Expansion in proteomics according to area of application 310
  • Growth trends in cell-based protein assay market 310
  • Challenges for development of cell-based protein assays 310
  • Future trends and prospects of cell-based protein assays 311
  • Strategic collaborations 311
  • Analysis of proteomics collaborations according to types of companies 311
  • Types of proteomic collaborations 312
  • Proteomics collaborations according to application areas 312
  • Analysis of proteomics collaborations: types of technologies 313
  • Collaborations based on protein biochip technology 313
  • Concluding remarks about proteomic collaborations 314
  • Proteomic patents 314
  • Market drivers in proteomics 315
  • Needs of the pharmaceutical industry 315
  • Need for outsourcing proteomic technologies 315
  • Funding of proteomic companies and research 315
  • Technical advances in proteomics 316
  • Changing trends in healthcare in future 316
  • Challenges facing proteomics 316
  • Magnitude and complexity of the task 316
  • Technical challenges 317
  • Limitations of proteomics 317
  • Limitations of 2DGE 317
  • Limitations of mass spectrometry techniques 317
  • Complexity of the pharmaceutical proteomics 318
  • Unmet needs in proteomics 318

11. Future of Proteomics 321

  • Genomics to proteomics 321
  • Faster technologies 321
  • FLEXGene repository 321
  • Need for new proteomic technologies 322
  • Emerging proteomic technologies 323
  • Detection of alternative protein isoforms 323
  • Direct protein identification in large genomes by mass spectrometry 323
  • Proteome identification kits with stacked membranes 323
  • Vacuum deposition interface 324
  • In vitro protein biosynthesis 324
  • Proteome mining with adenosine triphosphate 324
  • Proteome-scale purification of human proteins from bacteria 324
  • Proteostasis network 325
  • Cytoproteomics 325
  • Subcellular proteomics 325
  • Individual cell proteomics 326
  • Live cell proteomics 326
  • Fluorescent proteins for live-cell imaging 327
  • Membrane proteomics 327
  • Identification of membrane proteins by tandem MS of protein ions 327
  • Solid state NMR for study of nanocrystalline membrane proteins 328
  • Multiplex proteomics 328
  • High-throughput for proteomics 328
  • Future directions for protein biochip application 329
  • Bioinformatics for proteomics 329
  • High-Throughput Crystallography Consortium 329
  • Study of protein folding by IBM's Blue Gene 330
  • Study of proteins by atomic force microscopy 330
  • Population proteomics 330
  • Comparative proteome analysis 331
  • Human Proteome Organization 331
  • Cell-based Human Proteome Project 332
  • Human Salivary Proteome 332
  • Academic-commercial collaborations in proteomics 333
  • Indiana Centers for Applied Protein Sciences 333
  • Role of proteomics in the healthcare of the future 333
  • Proteomics and molecular medicine 333
  • Proteodiagnostics 334
  • Proteomics and personalized medicine 334
  • Targeting the ubiquitin pathway for personalized therapy of cancer 335
  • Protein patterns and personalized medicine 335
  • Personalizing interferon therapy of hepatitis C virus 337
  • Protein biochips and personalized medicine 337
  • Combination of diagnostics and therapeutics 338
  • Future prospects 338

12. References 339

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 29
  • Table 1-4: Methods of analysis at various levels of functional genomics 34
  • Table 2-1: Proteomics technologies 39
  • Table 2-2: Protein separation technologies of selected companies 44
  • Table 2-3: Companies supplying mass spectrometry instruments 52
  • Table 2-4: Companies involved in cell-based protein assays 73
  • Table 2-5: Methods used for the study of protein-protein interactions 75
  • Table 2-6: A selection of companies involved in protein-protein interaction studies 82
  • Table 2-7: Companies involved in Western blotting 98
  • Table 2-8: Proteomic technologies used with laser capture microdissection 99
  • Table 3-1: Applications of protein biochip technology 103
  • Table 3-2: Selected companies involved in protein biochip/microarray technology 119
  • Table 4-1: Proteomic databases and other Internet sources of proteomics information 127
  • Table 4-2: Protein interaction databases available on the Internet 133
  • Table 4-3: Bioinformatic tools for proteomics from academic sources 139
  • Table 4-4: Selected companies involved in bioinformatics for proteomics 140
  • Table 5-1: Applications of proteomics in basic biological research 143
  • Table 5-2: A sampling of proteomics research projects in academic institutions 159
  • Table 6-1: Pharmaceutical applications of proteomics 163
  • Table 6-2: Selected companies relevant to MALDI-MS for drug discovery 170
  • Table 6-3: Selected companies involved in GPCR-based drug discovery 178
  • Table 6-4: Companies involved in drug design based on structural proteomics 185
  • Table 6-5: Proteomic companies with high-throughput protein expression technologies 192
  • Table 6-6: Selected companies involved in chemogenomics/chemoproteomics 202
  • Table 6-7: Companies involved in glycoproteomic technologies 208
  • Table 7-1: Applications of proteomics in human healthcare 221
  • Table 7-2: Eye disorders and proteomic approaches 251
  • Table 8-1: Companies involved in applications of proteomics to oncology 278
  • Table 9-1: Neurodegenerative diseases with underlying protein abnormality 285
  • Table 9-2: Disease-specific proteins in the cerebrospinal fluid of patients 296
  • Table 10-1: Potential markets for proteomic technologies 2013-2023 303
  • Table 10-2: 2013 revenues of major companies from protein separation technologies 304
  • Table 10-3: Geographical distribution of markets for proteomic technologies 2013-2023 308
  • Table 11-1: Role of proteomics in personalizing strategies for cancer therapy 335

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. 32
  • Figure 1-4: Parallels between functional genomics and proteomics 32
  • Figure 2-1: Proteomics: flow from sample preparation to characterization 40
  • Figure 2-2: The central role of spectrometry in proteomics 47
  • Figure 2-3: Electrospray ionization (ESI) 48
  • Figure 2-4: Matrix-Assisted Laser Desorption/Ionization (MALDI) 50
  • Figure 2-5: Scheme of bio-bar-code assay 68
  • Figure 2-6: A diagrammatic presentation of yeast 2-hybrid system 81
  • Figure 3-1: ProteinChip System 105
  • Figure 3-2: Surface plasma resonance (SPR) 116
  • Figure 4-1: Role of bioinformatics in integrating genomic/proteomic-based drug discovery 126
  • Figure 4-2: Bottom-up and top-down approaches for protein sequencing 137
  • Figure 6-1: Drug discovery process 164
  • Figure 6-2: Regulatory changes induced by drugs and implemented at the proteins level. 167
  • Figure 6-3: Relation of proteome to genome, diseases and drugs 168
  • Figure 6-4: The mTOR pathways 182
  • Figure 6-5: Steps in shotgun proteomics 200
  • Figure 6-6: Chemogenomic approach to drug discovery (3-Dimensional Pharmaceuticals) 201
  • Figure 8-1: Relation of oncoproteomics to other technologies 257
  • Figure 9-1: A scheme of proteomics applications in CNS drug discovery and development 302
  • Figure 10-1: Types of companies involved in proteomics collaborations 312
  • Figure 10-2: Types of collaborations: R & D, licensing or marketing 312
  • Figure 10-3: Proteomics collaborations according to application areas 313
  • Figure 10-4: Proteomics collaborations according to technologies 313
  • Figure 10-5: Unmet needs in proteomics 319
  • Figure 11-1: A scheme of the role of proteomics in personalized management of cancer 337

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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