Market Research Report

Proteomics - Technologies, Markets and Companies

cover Published by Jain Pharmabiotech
Published Product code 70918
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Introduction

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 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 220 of these are profiled in the report with 462 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 2012 and are projected to years 2017 and 2022. The largest expansion will be in bioinformatics and protein biochip technologies. Important areas of application are cancer and neurological disorders

Table of Contents

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
  • Impact of the genetic factors on the human proteome 35
  • Proteomics and systems biology 36
  • Functional synthetic proteins 36

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
  • Companies involved in mass spectrometry 47
  • Electrospray ionization 48
  • Desorption electrospray ionization MS 49
  • Mirosaic 3500 MiD 50
  • Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 50
  • Cryogenic MALDI- Fourier Transform Mass Spectrometry 52
  • Stable-isotope-dilution tandem mass spectrometry 52
  • HUPO Gold MS Protein Standard 52
  • High performance liquid chromatography 53
  • 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 55
  • Quantification of low abundance proteins 55
  • SDS-PAGE 55
  • Antibodies and proteomics 56
  • 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 58
  • C-terminal peptide analysis 59
  • 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
  • RNA-Protein fusions 63
  • Designed repeat proteins 63
  • Application of nanbiotechnology to proteomics 63
  • Nanoproteomics 64
  • Protein nanocrystallography 64
  • Single-molecule mass spectrometry using a nanopore 64
  • Nanoelectrospray ionization 65
  • Nanoproteomics for discovery of protein biomarkers in the blood 65
  • Nanoparticle barcodes 65
  • Biobarcode assay for proteins 66
  • Nanopore-based protein sequencing 67
  • Nanoscale protein analysis 67
  • Nanoscale mechanism for protein engineering 68
  • Nanotube electronic biosensor 68
  • Nanotube-vesicle networks for study of membrane proteins 68
  • Nanowire transistor for the detection of protein-protein interactions 69
  • Qdot-nanocrystals 69
  • Resonance Light Scattering technology 69
  • Study of single membrane proteins at subnanometer resolution 70
  • Protein expression profiling 70
  • Cell-based protein assays 71
  • Living cell-based assays for protein function 71
  • Companies developing cell-based protein assays 72
  • Protein function studies 72
  • Transcriptionally Active PCR 73
  • Protein-protein interactions 73
  • Yeast two-hybrid system 74
  • Membrane one-hybrid method 75
  • Protein affinity chromatography 76
  • Phage display 76
  • Fluorescence Resonance Energy Transfer 76
  • Bioluminescence Resonance Energy Transfer 77
  • Detection Enhanced Ubiquitin Split Protein Sensor technology 77
  • Protein-fragment complementation system 77
  • In vivo study of protein-protein interactions 78
  • Bacterial protein interaction studies for assigning function 78
  • Computational prediction of interactions 78
  • Interactome 79
  • Protein-protein interactions and drug discovery 80
  • Companies with technologies for protein-protein interaction studies 80
  • Protein-DNA interaction 81
  • Determination of protein structure 81
  • X-Ray crystallography 82
  • Nuclear magnetic resonance 83
  • Electron spin resonance 83
  • Prediction of protein structure 83
  • Protein tomography 84
  • X-ray scattering-based method for determining the structure of proteins 84
  • Prediction of protein function 85
  • Three-dimensional proteomics for determination of function 85
  • An algorithm for genome-wide prediction of protein function 86
  • Monitoring protein function by expression profiling 86
  • Isotope-coded affinity tag peptide labeling 86
  • Differential Proteomic Panning 87
  • Cell map proteomics 87
  • Topological proteomics 88
  • Organelle or subcellular proteomics 89
  • Nucleolar proteomics 89
  • Glycoproteomic technologies 89
  • High-sensitivity glycoprotein analysis 89
  • Fluorescent in vivo imaging of glycoproteins 90
  • Integrated approaches for protein characterization 90
  • Imaging mass spectrometry 91
  • IMS technologies 91
  • Applications of IMS 91
  • The protein microscope 92
  • Tag-Mass IMS 92
  • Automation and robotics in proteomics 92
  • Western blot 93
  • Limitations of WB 93
  • Innovations in WB 93
  • Capillary electrophoresis and WB 94
  • Fluorescent WB 94
  • Microfluidics and WB 94
  • Multiplexing WB 95
  • Applications of Western blot 95
  • Research applications of Western blot 95
  • Molecular diagnostic applications of Western blot 96
  • Companies involved in Western blotting technologies 96
  • Laser capture microdissection 97
  • Microdissection techniques used for proteomics 97
  • Uses of LCM in combination with proteomic technologies 98
  • Concluding remarks about applications of proteomic technologies 98
  • Precision proteomics 99

3. Protein biochip technology 101

  • Introduction 101
  • Types of protein biochips 102
  • ProteinChip 102
  • Applications and advantages of ProteinChip 103
  • ProteinChip Biomarker System 103
  • Matrix-free ProteinChip Array 104
  • Aptamer-based protein biochip 104
  • Fluorescence planar wave guide technology-based protein biochips 105
  • Lab-on-a-chip for protein analysis 105
  • Biochips for peptide arrays 106
  • Microfluidic biochips for proteomics 106
  • Protein biochips for high-throughput expression 107
  • Nucleic Acid-Programmable Protein Array 107
  • High-density protein microarrays 107
  • HPLC-Chip for protein identification 108
  • Antibody microarrays 108
  • Integration of protein array and image analysis 108
  • Tissue microarray technology for proteomics 109
  • Protein biochips in molecular diagnostics 109
  • A force-based protein biochip 110
  • L1 chip and lipid immobilization 110
  • Multiplexed Protein Profiling on Microarrays 110
  • Live cell microarrays 111
  • ProteinArray Workstation 111
  • Proteome arrays 112
  • The Yeast ProtoArray 112
  • ProtoArray™ Human Protein Microarray 112
  • TRINECTIN proteome chip 113
  • Peptide arrays 113
  • Surface plasmon resonance technology 114
  • Biacore's SPR 114
  • FLEX CHIP 114
  • Combination of surface plasmon resonance and MALDI-TOF 115
  • Protein chips/microarrays using nanotechnology 115
  • Nanoparticle protein chip 115
  • Protein nanobiochip 116
  • Protein nanoarrays 116
  • Self-assembling protein nanoarrays 116
  • Companies involved in protein biochip/microarray technology 117

4. Bioinformatics in Relation to Proteomics 121

  • Introduction 121
  • Bioinformatic tools for proteomics 121
  • Testing of SELDI-TOF MS Proteomic Data 121
  • BioImagine's ProteinMine 122
  • Bioinformatics for pharmaceutical applications of proteomics 122
  • In silico search of drug targets by Biopendium 122
  • Compugen's LEADS 123
  • DrugScore 123
  • Proteochemometric modeling 123
  • Integration of genomic and proteomic data 124
  • Proteomic databases: creation and analysis 125
  • Introduction 125
  • Proteomic databases 125
  • GenProtEC 126
  • Human Protein Atlas 126
  • Human Proteomics Initiative 127
  • International Protein Index 128
  • Proteome maps 128
  • Protein Structure Initiative - Structural Genomics Knowledgebase 128
  • Protein Warehouse Database 128
  • Protein Data Bank 129
  • Repository for raw data from proteomics MS 129
  • Universal Protein Resource 129
  • Protein interaction databases 130
  • Biomolecular Interaction Network Database 131
  • ENCODE 131
  • Functional Genomics Consortium 131
  • Human Proteinpedia 132
  • ProteinCenter 132
  • Databases of the National Center for Biotechnology Information 132
  • Bioinformatics for protein identification 133
  • Application of bioinformatics in functional proteomics 133
  • Use of bioinformatics in protein sequencing 133
  • Bottom-up protein sequencing 134
  • Top-down protein sequencing 135
  • Protein structural database approach to drug design 135
  • Bioinformatics for high-throughput proteomics 135
  • Bioinformatics for protein-protein interactions 136
  • Companies with bioinformatic tools for proteomics 137

5. Research in Proteomics 139

  • Introduction 139
  • Applications of proteomics in biological research 139
  • Identification of novel human genes by comparative proteomics 139
  • Study of relationship between genes and proteins 140
  • Characterization of histone codes 140
  • Structural genomics or structural proteomics 141
  • Protein Structure Factory 142
  • Protein Structure Initiative 142
  • Studies on protein structure at Argonne National Laboratory 143
  • Structural Genomics Consortium 143
  • Protein knockout 144
  • Antisense approach and proteomics 144
  • RNAi and protein knockout 144
  • Total knockout of cellular proteins 144
  • Ribozymes and proteomics 145
  • Single molecule proteomics 145
  • Single-molecule photon stamping spectroscopy 145
  • Single nucleotide polymorphism determination by TOF-MS 146
  • Application of proteomic technologies in systems biology 146
  • Signaling pathways and proteomics 146
  • Kinomics 147
  • Combinatorial RNAi for quantitative protein network analysis 147
  • Proteomics in neuroscience research 147
  • Stem cell proteomics 148
  • Comparative proteomic analysis of somatic cells, iPSCs and ESCs 148
  • hESC phosphoproteome 149
  • Proteomic studies of mesenchymal stem cells 149
  • Proteomics of neural stem cells 150
  • Proteome Biology of Stem Cells Initiative 150
  • Proteomic analysis of the cell cycle 151
  • Nitric oxide and proteomics 151
  • A proteomic method for identification of cysteine S-nitrosylation sites 151
  • Study of the nitroproteome 152
  • Study of the phosphoproteome 152
  • Study of the mitochondrial proteome 153
  • Proteomic technologies for study of mitochondrial proteomics 153
  • Cryptome 154
  • Study of protein transport in health and disease 154
  • Ancient proteomics 154
  • Proteomics research in the academic sector 155
  • Netherlands Proteins@Work 157
  • ProteomeBinders initiative 157
  • Rutgers University's Center for Integrative Proteomics Research 157
  • Vanderbilt University's Center for Proteomics and Drug Actions 158

6. Pharmaceutical Applications of Proteomics 159

  • Introduction 159
  • Current drug discovery process and its limitations 159
  • Role of omics in drug discovery 160
  • Genomics-based drug discovery 160
  • Metabolomics technologies for drug discovery 161
  • Role of metabonomics in drug discovery 161
  • Basis of proteomics approach to drug discovery 162
  • Proteins and drug action 162
  • Transcription-aided drug design 163
  • Role of proteomic technologies in drug discovery 163
  • Liquid chromatography-based drug discovery 164
  • Capture compound mass spectrometry 165
  • Protein-expression mapping by 2DGE 165
  • Role of MALDI mass spectrometry in drug discovery 165
  • Structural proteomics and drug discovery 165
  • Tissue imaging mass spectrometry 166
  • Companies using MALDI for drug discovery 167
  • Oxford Genome Anatomy Project 168
  • Proteins as drug targets 168
  • Ligands to capture the purine binding proteome 169
  • Chemical probes to interrogate key protein families for drug discovery 169
  • Global proteomics for pharmacodynamics 169
  • CellCarta® proteomics platform 170
  • ZeptoMARK™ protein profiling system 170
  • Role of proteomics in targeting disease pathways 171
  • Dynamic proteomics 171
  • Identification of protein kinases as drug targets 171
  • Mechanisms of action of kinase inhibitors 172
  • G-protein coupled receptors as drug targets 172
  • Methods of study of GPCRs 173
  • Cell-based assays for GPCR 173
  • Companies involved in GPCR-based drug discovery 174
  • GPCR localization database 175
  • Matrix metalloproteases as drug targets 175
  • PDZ proteins as drug targets 176
  • Proteasome as drug target 176
  • Serine hydrolases as drug targets 177
  • Targeting mTOR signaling pathway 177
  • Targeting caspase-8 for anticancer therapeutics 178
  • Bioinformatic analysis of proteomics data for drug discovery 179
  • Drug design based on structural proteomics 179
  • Protein crystallography for determining 3D structure of proteins 179
  • Automated 3D protein modeling 180
  • Drug targeting of flexible dynamic proteins 180
  • Companies involved in structure-based drug-design 180
  • Integration of genomics and proteomics for drug discovery 181
  • Ligand-receptor binding 182
  • Role of proteomics in study of ligand-receptor binding 182
  • Aptamer protein binding 183
  • Systematic Evolution of Ligands by Exponential Enrichment 183
  • Aptamers and high-throughput screening 183
  • Nucleic Acid Biotools 184
  • Aptamer beacons 184
  • Peptide aptamers 185
  • Riboreporters for drug discovery 185
  • Target identification and validation 185
  • Application of mass spectrometry for target identification 186
  • Gene knockout and gene suppression for validating protein targets 186
  • Laser-mediated protein knockout for target validation 186
  • Integrated proteomics for drug discovery 187
  • High-throughput proteomics 187
  • Companies involved in high-throughput proteomics 188
  • Drug discovery through protein-protein interaction studies 188
  • Protein-protein interaction as basis for drug target identification 189
  • Protein-PCNA interaction as basis for drug design 189
  • Two-hybrid protein interaction technology for target identification 190
  • Biosensors for detection of small molecule-protein interactions 190
  • Protein-protein interaction maps 191
  • ProNet (Myriad Genetics) 191
  • Hybrigenics' maps of protein-protein interactions 191
  • CellZome's functional map of protein-protein interactions 192
  • Mapping of protein-protein interactions by mass spectrometry 192
  • Protein interaction map of Drosophila melanogaster 193
  • Protein-interaction map of Wellcome Trust Sanger Institute 193
  • Protein-protein interactions as targets for therapeutic intervention 193
  • Inhibition of protein-protein interactions by peptide aptamers 194
  • Selective disruption of proteins by small molecules 194
  • Post-genomic combinatorial biology approach 194
  • Differential proteomics 195
  • Shotgun proteomics 195
  • Chemogenomics/chemoproteomics for drug discovery 196
  • Chemoproteomics-based drug discovery 197
  • Companies involved in chemogenomics/chemoproteomics 198
  • Activity-based proteomics 199
  • Locus Discovery technology 199
  • Automated ligand identification system 200
  • Expression proteomics: protein level quantification 200
  • Role of phage antibody libraries in target discovery 201
  • Analysis of posttranslational modification of proteins by MS 201
  • Phosphoproteomics for drug discovery 202
  • Application of glycoproteomics for drug discovery 202
  • Role of carbohydrates in proteomics 202
  • Challenges of glycoproteomics 203
  • Companies involved in glycoproteomics 203
  • Role of protein microarrays/ biochips for drug discovery 204
  • Protein microarrays vs DNA microarrays for high-throughput screening 204
  • BIA-MS biochip for protein-protein interactions 204
  • ProteinChip with Surface Enhanced Neat Desorption 205
  • Protein-domains microarrays 205
  • Some limitations of protein biochips 205
  • Concluding remarks about role of proteomics in drug discovery 206
  • RNA versus protein profiling as guide to drug development 206
  • RNA as drug target 206
  • Combination of RNA and protein profiling 207
  • RNA binding proteins 208
  • Toxicoproteomics 208
  • Hepatotoxicity 208
  • Nephrotoxicity 209
  • Cardiotoxicity 209
  • Neurotoxicity 210
  • Protein/peptide therapeutics 210
  • Alphabody technology for improving protein therapeutics 210
  • Peptide-based drugs 210
  • Phylomer® peptides 211
  • Cryptein-based therapeutics 211
  • Synthetic proteins and peptides as pharmaceuticals 212
  • Genetic immunization and proteomics 212
  • Proteomics and gene therapy 213
  • Role of proteomics in clinical drug development 213
  • Pharmacoproteomics 214
  • Role of proteomics in clinical drug safety 214

7. Application of Proteomics in Human Healthcare 215

  • Introduction 215
  • Clinical proteomics 216
  • Definition and standards 216
  • Vermillion's Clinical Proteomics Program 216
  • Pathophysiology of human diseases 217
  • Diseases due to misfolding of proteins 217
  • Mechanism of protein folding 218
  • Nanoproteomics for study of misfolded proteins 219
  • Therapies for protein misfolding 219
  • Intermediate filament proteins 220
  • Significance of mitochondrial proteome in human disease 221
  • Proteome of Saccharomyces cerevisiae mitochondria 221
  • Rat mitochondrial proteome 221
  • Proteomic approaches to biomarker identification 222
  • The ideal biomarker 222
  • Proteomic technologies for biomarker discovery 222
  • MALDI mass spectrometry for biomarker discovery 223
  • BAMF™ Technology 223
  • Protein biochips/microarrays and biomarkers 224
  • Affinity proteomics for discovery of biomarkers 224
  • Antibody array-based biomarker discovery 224
  • Discovery of biomarkers by MAb microarray profiling 225
  • Tumor-specific serum peptidome patterns 225
  • Search for protein biomarkers in body fluids 226
  • Challenges and strategies for discovey of protein biomarkers in plasma 226
  • 3-D structure of CD38 as a biomarker 227
  • BD™ Free Flow Electrophoresis System 227
  • Isotope tags for relative and absolute quantification 227
  • N-terminal peptide isolation from human plasma 228
  • Plasma protein microparticles as biomarkers 228
  • Proteome partitioning 229
  • SISCAPA method for quantitating proteins and peptides in plasma 229
  • Stable isotope tagging methods 229
  • Technology to measure both the identity and size of the biomarker 230
  • Biomarkers in the urinary proteome 230
  • Application of proteomics in molecular diagnosis 231
  • Proximity ligation assay 232
  • Protein patterns 232
  • Proteomic tests on body fluids 232
  • Cyclical amplification of proteins 234
  • Applications of proteomics in infections 234
  • MALDI-TOF MS for microbial identification 234
  • Role of proteomics in virology 235
  • Study of interaction of proteins with viruses 235
  • Role of proteomics in bacteriology 236
  • Epidemiology of bacterial infections 236
  • Proteomic approach to bacterial pathogenesis 236
  • Vaccines for bacterial infections 236
  • Protein profiles associated with bacterial drug resistance 237
  • Analyses of the parasite proteome 237
  • Application of proteomics in cystic fibrosis 238
  • Proteomics of cardiovascular diseases 238
  • Pathomechanism of cardiovascular diseases 238
  • Protein misfolding in cardiac dysfunction 239
  • Study of cardiac mitochondrial proteome in myocardial ischemia 239
  • Cardiac protein databases 239
  • Proteomics of dilated cardiomyopathy and heart failure 240
  • Proteomic biomarkers of cardiovascular diseases 240
  • Role of proteomics in cardioprotection 241
  • Role of proteomics in heart transplantation 241
  • Future of application of proteomics in cardiology 241
  • Proteomic technologies for research in pulmonary disorders 242
  • Application of proteomics in renal disorders 243
  • Diagnosis of renal disorders 243
  • Proteomic biomarkers of acute kidney injury 243
  • Cystatin C as biomarker of glomerular filtration rate 244
  • Protein biomarkers of nephritis 244
  • Proteomics and kidney stones 244
  • Proteomics of eye disorders 244
  • Proteomics of cataract 245
  • Proteomics of diabetic retinopathy 246
  • Retinal dystrophies 246
  • Use of proteomics in inner ear disorders 246
  • Use of proteomics in aging research 246
  • Removal of altered cellular proteins in aging 247
  • Alteration of glycoproteins during aging 248
  • Proteomics and nutrition 248

8. Oncoproteomics 249

  • Introduction 249
  • Proteomic technologies for study of cancer 250
  • Application of CellCarta technology for oncology 250
  • Accentuation of differentially expressed proteins using phage technology 250
  • Cancer tissue proteomics 250
  • Dynamic cell proteomics in response to a drug 251
  • Desorption electrospray ionization for cancer diagnosis 251
  • Id proteins as targets for cancer therapy 252
  • Identification of oncogenic tyrosine kinases using phosphoproteomics 252
  • Laser capture microdissection technology and cancer proteomics 252
  • Mass spectrometry for identification of oncogenic chimeric proteins 253
  • Proteomic analysis of cancer cell mitochondria 253
  • Proteomic study of p53 254
  • Human Tumor Gene Index 254
  • Integration of cancer genomics and proteomics 254
  • Role of proteomics in study of cancer stem cell biology 255
  • Single-cell protein expression analysis by microfluidic techniques 255
  • Use of proteomics in cancers of various organ systems 255
  • Proteomics of brain tumors 255
  • Malignant glial tumors 255
  • Meningiomas 256
  • DESI-MS for intraoperative diagnosis of brain tumors 256
  • Proteomics of breast cancer 257
  • Integration of proteomic and genomic data for breast cancer 258
  • Proteomics of colorectal cancer 259
  • Proteomics of esophageal cancer 259
  • Proteomics of hepatic cancer 260
  • Proteomics of leukemia 260
  • Proteomics of lung cancer 261
  • Proteomics of pancreatic cancer 261
  • Proteomics of prostate cancer 262
  • Diagnostic use of cancer biomarkers 262
  • Proteomic technologies for tumor biomarkers 263
  • Nuclear matrix proteins (NMPs) 263
  • Antiannexins as tumor markers in lung cancer 264
  • NCI's Network of Clinical Proteomic Technology Centers 264
  • Proteomics and tumor immunology 265
  • Proteomics and study of tumor invasiveness 266
  • Anticancer drug discovery and development 266
  • Kinase-targeted drug discovery in oncology 266
  • Anticancer drug targeting: functional proteomics screen of proteases 267
  • Small molecule inhibitors of cancer-related proteins 267
  • Role of proteomics in studying drug resistance in cancer 268
  • Future prospects of oncoproteomics 268
  • Companies involved in application of proteomics to oncology 268

9. Neuroproteomics 271

  • Introduction 271
  • Application of proteomics for the study of nervous system 271
  • Proteomics of prion diseases 272
  • Normal function of prions in the brain 272
  • Diseases due to pathological prion protein 272
  • Transmissible spongiform encephalopathies 273
  • Creutzfeld-Jakob disease 273
  • Bovine spongiform encephalopathy 273
  • Variant Creutzfeldt-Jakob disease 274
  • Protein misfolding and neurodegenerative disorders 274
  • Ion channel link for protein-misfolding disease 274
  • Detection of misfolded proteins 274
  • Neurodegenerative disorders with protein abnormalities 275
  • Alzheimer disease 277
  • Common denominators of Alzheimer and prion diseases 277
  • Parkinson disease 278
  • Amyotrophic lateral sclerosis 278
  • Proteomics and glutamate repeat disorders 279
  • Proteomics and Huntington's disease 279
  • Proteomics and demyelinating diseases 280
  • Proteomics of neurogenetic disorders 280
  • Fabry disease 280
  • GM1 gangliosidosis 281
  • Quantitative proteomics and familial hemiplegic migraine 281
  • Proteomics of spinal muscular atrophy 282
  • Proteomics of CNS trauma 282
  • Proteomics of traumatic brain injury 282
  • Chronic traumatic encephalopathy and ALS 283
  • Proteomics of CNS aging 283
  • Protein aggregation as a bimarker of aging 283
  • Neuroproteomics of psychiatric disorders 284
  • Neuroproteomic of cocaine addiction 285
  • Neurodiagnostics based on proteomics 285
  • Disease-specific proteins in the cerebrospinal fluid 285
  • Tau proteins 286
  • CNS tissue proteomics 287
  • Diagnosis of CNS disorders by examination of proteins in urine 288
  • Diagnosis of CNS disorders by examination of proteins in the blood 288
  • Serum pNF-H as biomarker of CNS damage 289
  • Proteomics of BBB 289
  • Future prospects of neuroproteomics in neurology 290
  • HUPO's Pilot Brain Proteome Project 291

10. Proteomics Markets 293

  • Introduction 293
  • Potential markets for proteomic technologies 293
  • Bioinformatics markets for proteomics 294
  • Markets for protein separation technologies 294
  • Markets for 2D gel electrophoresis 294
  • Market trends in protein separation technolgies 295
  • Protein purification markets 295
  • Mass spectrometry markets 295
  • Markets for MALDI for drug discovery 296
  • Markets for nuclear magnetic resonance spectroscopy 296
  • Market for structure-based drug design 296
  • Markets for protein biomarkers 297
  • Markets for cell-based protein assays 297
  • Protein biochip markets 297
  • Western blot markets 297
  • Geographical distribution of proteomics technologies markets 298
  • Business and strategic considerations 298
  • Cost of protein structure determination 298
  • Opinion surveys of the scientist consumers of proteomic technologies 298
  • Opinions on mass spectrometry 298
  • Opinions on bioinformatics and proteomic databases 299
  • Systems for in vivo study of protein-protein interactions 299
  • Perceptions of the value of protein biochip/microfluidic systems 299
  • Small versus big companies 299
  • Expansion in proteomics according to area of application 300
  • Growth trends in cell-based protein assay market 300
  • Challenges for development of cell-based protein assays 300
  • Future trends and prospects of cell-based protein assays 301
  • Strategic collaborations 301
  • Analysis of proteomics collaborations according to types of companies 301
  • Types of proteomic collaborations 302
  • Proteomics collaborations according to application areas 302
  • Analysis of proteomics collaborations: types of technologies 303
  • Collaborations based on protein biochip technology 303
  • Concluding remarks about proteomic collaborations 304
  • Proteomic patents 304
  • Market drivers in proteomics 305
  • Needs of the pharmaceutical industry 305
  • Need for outsourcing proteomic technologies 305
  • Funding of proteomic companies and research 305
  • Technical advances in proteomics 306
  • Changing trends in healthcare in future 306
  • Challenges facing proteomics 306
  • Magnitude and complexity of the task 306
  • Technical challenges 307
  • Limitations of proteomics 307
  • Limitations of 2DGE 307
  • Limitations of mass spectrometry techniques 307
  • Complexity of the pharmaceutical proteomics 308
  • Unmet needs in proteomics 308

11. Future of Proteomics 311

  • Genomics to proteomics 311
  • Faster technologies 311
  • FLEXGene repository 311
  • Need for new proteomic technologies 312
  • Emerging proteomic technologies 313
  • Detection of alternative protein isoforms 313
  • Direct protein identification in large genomes by mass spectrometry 313
  • Proteome identification kits with stacked membranes 313
  • Vacuum deposition interface 314
  • In vitro protein biosynthesis 314
  • Proteome mining with adenosine triphosphate 314
  • Proteome-scale purification of human proteins from bacteria 314
  • Proteostasis network 315
  • Cytoproteomics 315
  • Subcellular proteomics 315
  • Individual cell proteomics 316
  • Live cell proteomics 316
  • Fluorescent proteins for live-cell imaging 317
  • Membrane proteomics 317
  • Identification of membrane proteins by tandem MS of protein ions 317
  • Solid state NMR for study of nanocrystalline membrane proteins 318
  • Multiplex proteomics 318
  • High-throughput for proteomics 318
  • Future directions for protein biochip application 319
  • Bioinformatics for proteomics 319
  • High-Throughput Crystallography Consortium 319
  • Study of protein folding by IBM's Blue Gene 320
  • Study of proteins by atomic force microscopy 320
  • Population proteomics 320
  • Comparative proteome analysis 321
  • Human Proteome Organization 321
  • Cell-based Human Proteome Project 322
  • Human Salivary Proteome 322
  • Academic-commercial collaborations in proteomics 323
  • Indiana Centers for Applied Protein Sciences 323
  • Role of proteomics in the healthcare of the future 323
  • Proteomics and molecular medicine 323
  • Proteodiagnostics 324
  • Proteomics and personalized medicine 324
  • Targeting the ubiquitin pathway for personalized therapy of cancer 325
  • Protein patterns and personalized medicine 325
  • Personalizing interferon therapy of hepatitis C virus 327
  • Protein biochips and personalized medicine 327
  • Combination of diagnostics and therapeutics 328
  • Future prospects 328

12. References 329

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 39
  • Table 2-2: Protein separation technologies of selected companies 44
  • Table 2-3: Companies supplying mass spectrometry instruments 47
  • Table 2-4: Companies involved in cell-based protein assays 72
  • Table 2-5: Methods used for the study of protein-protein interactions 73
  • Table 2-6: A selection of companies involved in protein-protein interaction studies 80
  • Table 2-7: Companies involved in Western blotting 96
  • Table 2-8: Proteomic technologies used with laser capture microdissection 98
  • Table 3-1: Applications of protein biochip technology 101
  • Table 3-2: Selected companies involved in protein biochip/microarray technology 117
  • Table 4-1: Proteomic databases and other Internet sources of proteomics information 125
  • Table 4-2: Protein interaction databases available on the Internet 130
  • Table 4-3: Bioinformatic tools for proteomics from academic sources 136
  • Table 4-4: Selected companies involved in bioinformatics for proteomics 137
  • Table 5-1: Applications of proteomics in basic biological research 139
  • Table 5-2: A sampling of proteomics research projects in academic institutions 155
  • Table 6-1: Pharmaceutical applications of proteomics 159
  • Table 6-2: Selected companies relevant to MALDI-MS for drug discovery 167
  • Table 6-3: Selected companies involved in GPCR-based drug discovery 174
  • Table 6-4: Companies involved in drug design based on structural proteomics 181
  • Table 6-5: Proteomic companies with high-throughput protein expression technologies 188
  • Table 6-6: Selected companies involved in chemogenomics/chemoproteomics 198
  • Table 6-7: Companies involved in glycoproteomic technologies 203
  • Table 7-1: Applications of proteomics in human healthcare 215
  • Table 7-2: Eye disorders and proteomic approaches 245
  • Table 8-1: Companies involved in applications of proteomics to oncology 269
  • Table 9-1: Neurodegenerative diseases with underlying protein abnormality 275
  • Table 9-2: Disease-specific proteins in the cerebrospinal fluid of patients 285
  • Table 10-1: Potential markets for proteomic technologies 2012-2022 293
  • Table 10-2: 2012 revenues of major companies from protein separation technologies 294
  • Table 10-3: Geographical distribution of markets for proteomic technologies 2012-2022 298
  • Table 11-1: Role of proteomics in personalizing strategies for cancer therapy 325

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 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) 51
  • Figure 2-5: Scheme of bio-bar-code assay 66
  • Figure 2-6: A diagrammatic presentation of yeast two-hybrid system 75
  • Figure 3-1: ProteinChip System 103
  • Figure 3-2: Surface plasma resonance (SPR) 114
  • Figure 4-1: Role of bioinformatics in integrating genomic/proteomic-based drug discovery 124
  • Figure 4-2: Bottom-up and top-down approaches for protein sequencing 134
  • Figure 6-1: Drug discovery process 160
  • Figure 6-2: Regulatory changes induced by drugs and implemented at the proteins level. 163
  • Figure 6-3: Relation of proteome to genome, diseases and drugs 164
  • Figure 6-4: The mTOR pathways 178
  • Figure 6-5: Steps in shotgun proteomics 196
  • Figure 6-6: Chemogenomic approach to drug discovery (3-Dimensional Pharmaceuticals) 197
  • Figure 8-1: Relation of oncoproteomics to other technologies 249
  • Figure 9-1: A scheme of proteomics applications in CNS drug discovery and development 290
  • Figure 10-1: Types of companies involved in proteomics collaborations 302
  • Figure 10-2: Types of collaborations: R & D, licensing or marketing 302
  • Figure 10-3: Proteomics collaborations according to application areas 303
  • Figure 10-4: Proteomics collaborations according to technologies 303
  • Figure 10-5: Unmet needs in proteomics 309
  • Figure 11-1: A scheme of the role of proteomics in personalized management of cancer 327

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

Proteomics - Technologies, Markets and Companies published by Jain Pharmabiotech in April 1, 2013. This report price starts from US $ 5000.

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