Proteomics - Technologies, Markets and Companies

NEW YORK, Nov. 30, 2011 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:

Proteomics - Technologies, Markets and Companies

http://www.reportlinker.com/p0203550/Proteomics---Technologies-Markets-and-Companies.html#utm_source=prnewswire&utm_medium=pr&utm_campaign=Genomics

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 480 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 2010 and are projected to years 2015 and 2020. The largest expansion will be in bioinformatics and protein biochip technologies. Important areas of application are cancer and neurological disorders

TABLE OF CONTENTS

0. Executive Summary 15

1. Basics of Proteomics 17

Introduction 17

History 17

Nucleic acids, genes and proteins 18

Genome 18

DNA 19

RNA 19

MicroRNAs 19

Decoding of mRNA by the ribosome 20

Genes 21

Alternative splicing 21

Transcription 22

Gene regulation 22

Gene expression 23

Chromatin 23

Golgi complex 24

Proteins 24

Spliceosome 25

Functions of proteins 25

Inter-relationship of protein, mRNA and DNA 26

Proteomics 27

Mitochondrial proteome 28

S-nitrosoproteins in mitochondria 28

Proteomics and genomics 29

Classification of proteomics 31

Levels of functional genomics and various "omics" 31

Glycoproteomics 32

Transcriptomics 32

Metabolomics 32

Cytomics 33

Phenomics 33

Proteomics and systems biology 33

Functional synthetic proteins 34

2. Proteomic Technologies 35

Key technologies driving proteomics 35

Sample preparation 36

New trends in sample preparation 36

Pressure Cycling Technology 37

Protein separation technologies 37

High resolution 2D gel electrophoresis 37

Variations of 2D gel technology 38

Limitations of 2DGE and measures to overcome these 38

1-D sodium dodecyl sulfate (SDS) PAGE 38

Capillary electrophoresis systems 39

Head column stacking capillary zone electrophoresis 39

Removal of albumin and IgG 39

Companies with protein separation technologies 40

Protein detection 41

Protein identification and characterization 42

Mass spectrometry (MS) 42

Companies involved in mass spectrometry 42

Electrospray ionization 43

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 44

Cryogenic MALDI- Fourier Transform Mass Spectrometry 45

Stable-isotope-dilution tandem mass spectrometry 46

HUPO Gold MS Protein Standard 46

High performance liquid chromatography 46

Multidimensional protein identification technology (MudPIT) 47

Peptide mass fingerprinting 47

Combination of protein separation technologies with mass spectrometry 47

Combining capillary electrophoresis with mass spectrometry 47

2D PAGE and mass spectrometry 48

Quantification of low abundance proteins 48

SDS-PAGE 48

Antibodies and proteomics 49

Detection of fusion proteins 49

Labeling and detection of proteins 49

Fluorescent labeling of proteins in living cells 50

Combination of microspheres with fluorescence 50

Self-labeling protein tags 51

Analysis of peptides 51

C-terminal peptide analysis 52

Differential Peptide Display 52

Peptide analyses using NanoLC-MS 53

Protein sequencing 53

Real-time PCR for protein quantification 54

Quantitative proteomics 54

MS-based quantitative proteomics 54

MS and cryo-electron tomography 55

Functional proteomics: technologies for studying protein function 55

Functional genomics by mass spectrometry 55

RNA-Protein fusions 55

Designed repeat proteins 56

Application of nanbiotechnology to proteomics 56

Nanoproteomics 56

Protein nanocrystallography 57

Single-molecule mass spectrometry using a nanopore 57

Nanoelectrospray ionization 57

Nanoparticle barcodes 58

Biobarcode assay for proteins 58

Nanobiotechnology for discovery of protein biomarkers in the blood 60

Nanoscale protein analysis 60

Nanoscale mechanism for protein engineering 61

Nanotube electronic biosensor 61

Nanotube-vesicle networks for study of membrane proteins 62

Nanowire transistor for the detection of protein-protein interactions 62

Qdot-nanocrystals 62

Resonance Light Scattering technology 63

Study of single membrane proteins at subnanometer resolution 63

Protein expression profiling 63

Cell-based protein assays 64

Living cell-based assays for protein function 65

Companies developing cell-based protein assays 65

Protein function studies 66

Transcriptionally Active PCR 66

Protein-protein interactions 66

Yeast two-hybrid system 68

Membrane one-hybrid method 69

Protein affinity chromatography 69

Phage display 69

Fluorescence Resonance Energy Transfer 70

Bioluminescence Resonance Energy Transfer 70

Detection Enhanced Ubiquitin Split Protein Sensor technology 70

Protein-fragment complementation system 71

In vivo study of protein-protein interactions 71

Computational prediction of interactions 72

Interactome 72

Protein-protein interactions and drug discovery 73

Companies with technologies for protein-protein interaction studies 73

Protein-DNA interaction 74

Determination of protein structure 74

X-Ray crystallography 75

Nuclear magnetic resonance 76

Electron spin resonance 76

Prediction of protein structure 76

Protein tomography 77

X-ray scattering-based method for determining the structure of proteins 78

Prediction of protein function 78

Three-dimensional proteomics for determination of function 79

An algorithm for genome-wide prediction of protein function 79

Monitoring protein function by expression profiling 79

Isotope-coded affinity tag peptide labeling 80

Differential Proteomic Panning 80

Cell map proteomics 81

Topological proteomics 81

Organelle or subcellular proteomics 82

Nucleolar proteomics 82

Glycoproteomic technologies 83

High-sensitivity glycoprotein analysis 83

Fluorescent in vivo imaging of glycoproteins 83

Integrated approaches for protein characterization 83

Imaging mass spectrometry 84

IMS technologies 84

Applications of IMS 84

The protein microscope 85

Automation and robotics in proteomics 85

Laser capture microdissection 86

Microdissection techniques used for proteomics 86

Uses of LCM in combination with proteomic technologies 86

Concluding remarks about applications of proteomic technologies 87

Precision proteomics 87

3. Protein biochip technology 89

Introduction 89

Types of protein biochips 90

ProteinChip 90

Applications and advantages of ProteinChip 91

ProteinChip Biomarker System 91

Matrix-free ProteinChip Array 92

Aptamer-based protein biochip 92

Fluorescence planar wave guide technology-based protein biochips 93

Lab-on-a-chip for protein analysis 93

Microfluidic biochips for proteomics 94

Protein biochips for high-throughput expression 95

Nucleic Acid-Programmable Protein Array 95

High-density protein microarrays 95

HPLC-Chip for protein identification 95

Antibody microarrays 96

Integration of protein array and image analysis 96

Tissue microarray technology for proteomics 96

Protein biochips in molecular diagnostics 97

A force-based protein biochip 98

L1 chip and lipid immobilization 98

Multiplexed Protein Profiling on Microarrays 98

Live cell microarrays 99

ProteinArray Workstation 99

Proteome arrays 100

The Yeast ProtoArray 100

ProtoArray? Human Protein Microarray 100

TRINECTIN proteome chip 101

Peptide arrays 101

Surface plasmon resonance technology 102

Biacore's SPR 102

FLEX CHIP 102

Combination of surface plasmon resonance and MALDI-TOF 103

Protein chips/microarrays using nanotechnology 103

Nanoparticle protein chip 103

Protein nanobiochip 103

Protein nanoarrays 104

Self-assembling protein nanoarrays 104

Companies involved in protein biochip/microarray technology 105

4. Bioinformatics in Relation to Proteomics 109

Introduction 109

Bioinformatic tools for proteomics 109

Testing of SELDI-TOF MS Proteomic Data 109

BioImagine's ProteinMine 110

Bioinformatics for pharmaceutical applications of proteomics 110

In silico search of drug targets by Biopendium 110

Compugen's LEADS 111

DrugScore 111

Proteochemometric modeling 111

Integration of genomic and proteomic data 112

Proteomic databases: creation and analysis 113

Introduction 113

Proteomic databases 113

GenProtEC 114

Human Protein Atlas 114

Human Proteomics Initiative 115

International Protein Index 116

Proteome maps 116

Protein Structure Initiative ? Structural Genomics Knowledgebase 116

Protein Warehouse Database 116

Protein Data Bank 117

Universal Protein Resource 117

Protein interaction databases 117

Biomolecular Interaction Network Database 118

ENCODE 118

Functional Genomics Consortium 119

Human Proteinpedia 119

ProteinCenter 119

Databases of the National Center for Biotechnology Information 120

Bioinformatics for protein identification 120

Application of bioinformatics in functional proteomics 120

Use of bioinformatics in protein sequencing 121

Bottom-up protein sequencing 121

Top-down protein sequencing 122

Protein structural database approach to drug design 122

Bioinformatics for high-throughput proteomics 123

Companies with bioinformatic tools for proteomics 124

5. Research in Proteomics 125

Introduction 125

Applications of proteomics in biological research 125

Identification of novel human genes by comparative proteomics 125

Study of relationship between genes and proteins 126

Characterization of histone codes 126

Structural genomics or structural proteomics 127

Protein Structure Factory 128

Protein Structure Initiative 128

Studies on protein structure at Argonne National Laboratory 129

Structural Genomics Consortium 129

Protein knockout 130

Antisense approach and proteomics 130

RNAi and protein knockout 130

Total knockout of cellular proteins 130

Ribozymes and proteomics 131

Single molecule proteomics 131

Single-molecule photon stamping spectroscopy 131

Single nucleotide polymorphism determination by TOF-MS 132

Application of proteomic technologies in systems biology 132

Signaling pathways and proteomics 132

Kinomics 133

Combinatorial RNAi for quantitative protein network analysis 133

Proteomics in neuroscience research 133

Stem cell proteomics 134

hESC phosphoproteome 134

Proteomic studies of mesenchymal stem cells 135

Proteomics of neural stem cells 135

Proteome Biology of Stem Cells Initiative 136

Proteomic analysis of the cell cycle 137

Nitric oxide and proteomics 137

A proteomic method for identification of cysteine S-nitrosylation sites 137

Study of the nitroproteome 137

Study of the phosphoproteome 138

Study of the mitochondrial proteome 138

Proteomic technologies for study of mitochondrial proteomics 139

Cryptome 139

Study of protein transport in health and disease 139

Proteomics research in the academic sector 140

Vanderbilt University's Center for Proteomics and Drug Actions 142

ProteomeBinders initiative 142

6. Pharmaceutical Applications of Proteomics 143

Introduction 143

Current drug discovery process and its limitations 143

Role of omics in drug discovery 144

Genomics-based drug discovery 144

Metabolomics technologies for drug discovery 145

Role of metabonomics in drug discovery 145

Basis of proteomics approach to drug discovery 146

Proteins and drug action 146

Transcription-aided drug design 147

Role of proteomic technologies in drug discovery 147

Liquid chromatography-based drug discovery 148

Capture compound mass spectrometry 149

Protein-expression mapping by 2DGE 149

Role of MALDI mass spectrometry in drug discovery 149

Tissue imaging mass spectrometry 149

Companies using MALDI for drug discovery 151

Oxford Genome Anatomy Project 151

Proteins as drug targets 152

Ligands to capture the purine binding proteome 152

Chemical probes to interrogate key protein families for drug discovery 152

Global proteomics for pharmacodynamics 153

CellCarta® proteomics platform 153

ZeptoMARK? protein profiling system 154

Role of proteomics in targeting disease pathways 154

Identification of protein kinases as drug targets 154

Mechanisms of action of kinase inhibitors 155

G-protein coupled receptors as drug targets 155

Methods of study of GPCRs 156

Cell-based assays for GPCR 156

Companies involved in GPCR-based drug discovery 157

GPCR localization database 158

Matrix metalloproteases as drug targets 158

PDZ proteins as drug targets 159

Proteasome as drug target 159

Serine hydrolases as drug targets 160

Targeting mTOR signaling pathway 160

Targeting caspase-8 for anticancer therapeutics 161

Bioinformatic analysis of proteomics data for drug discovery 162

Drug design based on structural proteomics 162

Protein crystallography for determining 3D structure of proteins 162

Automated 3D protein modeling 163

Drug targeting of flexible dynamic proteins 163

Companies involved in structure-based drug-design 163

Integration of genomics and proteomics for drug discovery 164

Ligand-receptor binding 165

Role of proteomics in study of ligand-receptor binding 165

Aptamer protein binding 166

Systematic Evolution of Ligands by Exponential Enrichment 166

Aptamers and high-throughput screening 166

Nucleic Acid Biotools 167

Aptamer beacons 167

Peptide aptamers 168

Riboreporters for drug discovery 168

Target identification and validation 168

Application of mass spectrometry for target identification 169

Gene knockout and gene suppression for validating protein targets 169

Laser-mediated protein knockout for target validation 169

Integrated proteomics for drug discovery 170

High-throughput proteomics 170

Companies involved in high-throughput proteomics 171

Drug discovery through protein-protein interaction studies 171

Protein-protein interaction as basis for drug target identification 172

Protein-PCNA interaction as basis for drug design 172

Two-hybrid protein interaction technology for target identification 173

Biosensors for detection of small molecule-protein interactions 173

Protein-protein interaction maps 174

ProNet (Myriad Genetics) 174

Hybrigenics' maps of protein-protein interactions 174

CellZome's functional map of protein-protein interactions 175

Mapping of protein-protein interactions by mass spectrometry 175

Protein interaction map of Drosophila melanogaster 176

Protein-interaction map of Wellcome Trust Sanger Institute 176

Protein-protein interactions as targets for therapeutic intervention 176

Inhibition of protein-protein interactions by peptide aptamers 177

Selective disruption of proteins by small molecules 177

Post-genomic combinatorial biology approach 177

Differential proteomics 178

Shotgun proteomics 178

Chemogenomics/chemoproteomics for drug discovery 179

Chemoproteomics-based drug discovery 180

Companies involved in chemogenomics/chemoproteomics 181

Activity-based proteomics 182

Locus Discovery technology 182

Automated ligand identification system 183

Expression proteomics: protein level quantification 183

Role of phage antibody libraries in target discovery 184

Analysis of posttranslational modification of proteins by MS 184

Phosphoproteomics for drug discovery 185

Application of glycoproteomics for drug discovery 185

Role of carbohydrates in proteomics 185

Challenges of glycoproteomics 186

Companies involved in glycoproteomics 186

Role of protein microarrays/ biochips for drug discovery 187

Protein microarrays vs DNA microarrays for high-throughput screening 187

BIA-MS biochip for protein-protein interactions 187

ProteinChip with Surface Enhanced Neat Desorption 188

Protein-domains microarrays 188

Some limitations of protein biochips 188

Concluding remarks about role of proteomics in drug discovery 189

RNA versus protein profiling as guide to drug development 189

RNA as drug target 189

Combination of RNA and protein profiling 190

RNA binding proteins 191

Toxicoproteomics 191

Hepatotoxicity 191

Nephrotoxicity 192

Cardiotoxicity 192

Neurotoxicity 193

Protein/peptide therapeutics 193

Peptide-based drugs 193

Phylomer® peptides 194

Cryptein-based therapeutics 194

Synthetic proteins and peptides as pharmaceuticals 195

Genetic immunization and proteomics 195

Proteomics and gene therapy 196

Role of proteomics in clinical drug development 196

Pharmacoproteomics 196

Role of proteomics in clinical drug safety 197

7. Application of Proteomics in Human Healthcare 199

Introduction 199

Clinical proteomics 200

Definition and standards 200

Vermillion's Clinical Proteomics Program 200

Pathophysiology of human diseases 201

Diseases due to misfolding of proteins 201

Mechanism of protein folding 202

Nanoproteomics for study of misfolded proteins 203

Therapies for protein misfolding 203

Intermediate filament proteins 204

Significance of mitochondrial proteome in human disease 205

Proteome of Saccharomyces cerevisiae mitochondria 205

Rat mitochondrial proteome 205

Proteomic approaches to biomarker identification 206

The ideal biomarker 206

Proteomic technologies for biomarker discovery 206

MALDI mass spectrometry for biomarker discovery 207

BAMF? Technology 207

Protein biochips/microarrays and biomarkers 208

Antibody-based biomarker discovery 208

Tumor-specific serum peptidome patterns 208

Search for protein biomarkers in body fluids 209

Challenges and strategies for discovey of protein biomarkers in plasma 209

3-D structure of CD38 as a biomarker 210

BD™ Free Flow Electrophoresis System 210

Isotope tags for relative and absolute quantification 211

N-terminal peptide isolation from human plasma 211

Plasma protein microparticles as biomarkers 211

Proteome partitioning 212

SISCAPA method for quantitating proteins and peptides in plasma 212

Stable isotope tagging methods 212

Technology to measure both the identity and size of the biomarker 213

Biomarkers in the urinary proteome 213

Application of proteomics in molecular diagnosis 214

Proximity ligation assay 215

Protein patterns 215

Proteomic tests on body fluids 215

Cyclical amplification of proteins 217

Applications of proteomics in infections 217

Mass spectrometry for microbial identification 217

Role of proteomics in virology 218

Study of interaction of proteins with viruses 218

Role of proteomics in bacteriology 218

Epidemiology of bacterial infections 219

Proteomic approach to bacterial pathogenesis 219

Vaccines for bacterial infections 219

Protein profiles associated with bacterial drug resistance 220

Analyses of the parasite proteome 220

Application of proteomics in cystic fibrosis 221

Proteomics of cardiovascular diseases 221

Pathomechanism of cardiovascular diseases 221

Study of cardiac mitochondrial proteome in myocardial ischemia 221

Cardiac protein databases 222

Proteomics of dilated cardiomyopathy and heart failure 222

Proteomic biomarkers of cardiovascular diseases 223

Role of proteomics in cardioprotection 223

Role of proteomics in heart transplantation 223

Future of application of proteomics in cardiology 224

Proteomic technologies for research in pulmonary disorders 224

Application of proteomics in renal disorders 225

Diagnosis of renal disorders 225

Proteomic biomarkers of acute kidney injury 226

Cystatin C as biomarker of glomerular filtration rate 226

Protein biomarkers of nephritis 226

Proteomics and kidney stones 227

Proteomics of eye disorders 227

Proteomics of cataract 227

Proteomics of diabetic retinopathy 228

Retinal dystrophies 228

Use of proteomics in inner ear disorders 229

Use of proteomics in aging research 229

Removal of altered cellular proteins in aging 230

Alteration of glycoproteins during aging 230

Proteomics and nutrition 230

8. Oncoproteomics 231

Introduction 231

Proteomic technologies for study of cancer 232

Application of CellCarta technology for oncology 232

Accentuation of differentially expressed proteins using phage technology 232

Identification of oncogenic tyrosine kinases using phosphoproteomics 232

Single-cell protein expression analysis by microfluidic techniques 233

Dynamic cell proteomics in response to a drug 233

Desorption electrospray ionization for cancer diagnosis 233

Proteomic analysis of cancer cell mitochondria 234

Mass spectrometry for identification of oncogenic chimeric proteins 234

Id proteins as targets for cancer therapy 235

Proteomic study of p53 235

Human Tumor Gene Index 235

Integration of cancer genomics and proteomics 236

Laser capture microdissection technology and cancer proteomics 236

Cancer tissue proteomics 237

Use of proteomics in cancers of various organ systems 237

Proteomics of brain tumors 237

Proteomics of breast cancer 238

Proteomics of colorectal cancer 239

Proteomics of esophageal cancer 240

Proteomics of hepatic cancer 240

Proteomics of leukemia 240

Proteomics of lung cancer 241

Proteomics of pancreatic cancer 241

Proteomics of prostate cancer 242

Diagnostic use of cancer biomarkers 243

Proteomic technologies for tumor biomarkers 243

Nuclear matrix proteins (NMPs) 244

Antiannexins as tumor markers in lung cancer 244

NCI's Network of Clinical Proteomic Technology Centers 245

Proteomics and tumor immunology 246

Proteomics and study of tumor invasiveness 246

Anticancer drug discovery and development 246

Kinase-targeted drug discovery in oncology 247

Anticancer drug targeting: functional proteomics screen of proteases 248

Small molecule inhibitors of cancer-related proteins 248

Role of proteomics in studying drug resistance in cancer 248

Future prospects of oncoproteomics 249

Companies involved in application of proteomics to oncology 249

9. Neuroproteomics 251

Introduction 251

Proteomics of prion diseases 251

Transmissible spongiform encephalopathies 252

Creutzfeld-Jakob disease 252

Bovine spongiform encephalopathy 253

Variant Creutzfeldt-Jakob disease 253

Protein misfolding and neurodegenerative disorders 253

Ion channel link for protein-misfolding disease 253

Detection of misfolded proteins 254

Neurodegenerative disorders with protein abnormalities 254

Alzheimer disease 256

Common denominators of Alzheimer and prion diseases 256

Parkinson disease 257

Amyotrophic lateral sclerosis 257

Proteomics and glutamate repeat disorders 258

Proteomics and Huntington's disease 258

Proteomics and demyelinating diseases 259

Proteomics of neurogenetic disorders 259

Fabry disease 259

GM1 gangliosidosis 260

Quantitative proteomics and familial hemiplegic migraine 260

Proteomics of spinal muscular atrophy 261

Proteomics of CNS trauma 261

Proteomics of traumatic brain injury 261

Chronic traumatic encephalopathy and ALS 262

Proteomics of CNS aging 262

Protein aggregation as a bimarker of aging 262

Neuroproteomics of psychiatric disorders 263

Neuroproteomic of cocaine addiction 263

Neurodiagnostics based on proteomics 264

Disease-specific proteins in the cerebrospinal fluid 264

Tau proteins 265

CNS tissue proteomics 265

Diagnosis of CNS disorders by examination of proteins in urine 267

Diagnosis of CNS disorders by examination of proteins in the blood 267

Serum pNF-H as biomarker of CNS damage 268

Proteomics of BBB 268

Future prospects of neuroproteomics in neurology 269

HUPO's Pilot Brain Proteome Project 270

10. Commercial Aspects of Proteomics 271

Introduction 271

Potential markets for proteomic technologies 271

Geographical distribution of proteomics technologies markets 272

Markets for protein separation technologies 272

Markets for 2D gel electrophoresis 273

Trends in protein separation technolgies and effect on market 273

Protein biochip markets 273

Mass spectrometry markets 274

Markets for MALDI for drug discovery 274

Markets for nuclear magnetic resonance spectroscopy 274

Market for structure-based drug design 275

Bioinformatics markets for proteomics 275

Markets for protein biomarkers 275

Markets for cell-based protein assays 275

Business and strategic considerations 276

Cost of protein structure determination 276

Opinion surveys of the scientist consumers of proteomic technologies 276

Opinions on mass spectrometry 276

Opinions on bioinformatics and proteomic databases 276

Systems for in vivo study of protein-protein interactions 277

Perceptions of the value of protein biochip/microfluidic systems 277

Small versus big companies 277

Expansion in proteomics according to area of application 277

Growth trends in cell-based protein assay market 278

Challenges for development of cell-based protein assays 278

Future trends and prospects of cell-based protein assays 278

Strategic collaborations 279

Analysis of proteomics collaborations according to types of companies 279

Types of proteomic collaborations 280

Proteomics collaborations according to application areas 280

Analysis of proteomics collaborations: types of technologies 280

Collaborations based on protein biochip technology 281

Concluding remarks about proteomic collaborations 281

Proteomic patents 282

Market drivers in proteomics 282

Needs of the pharmaceutical industry 282

Need for outsourcing proteomic technologies 283

Funding of proteomic companies and research 283

Technical advances in proteomics 283

Changing trends in healthcare in future 284

Challenges facing proteomics 284

Magnitude and complexity of the task 284

Technical challenges 284

Limitations of proteomics 285

Limitations of 2DGE 285

Limitations of mass spectrometry techniques 285

Complexity of the pharmaceutical proteomics 285

Unmet needs in proteomics 286

11. Future of Proteomics 287

Genomics to proteomics 287

Faster technologies 287

FLEXGene repository 287

Need for new proteomic technologies 288

Emerging proteomic technologies 289

Detection of alternative protein isoforms 289

Direct protein identification in large genomes by mass spectrometry 289

Proteome identification kits with stacked membranes 289

Vacuum deposition interface 290

In vitro protein biosynthesis 290

Proteome mining with adenosine triphosphate 290

Proteome-scale purification of human proteins from bacteria 290

Proteostasis network 291

Cytoproteomics 291

Subcellular proteomics 291

Individual cell proteomics 292

Live cell proteomics 292

Fluorescent proteins for live-cell imaging 293

Membrane proteomics 293

Identification of membrane proteins by tandem MS of protein ions 293

Solid state NMR for study of nanocrystalline membrane proteins 294

Multiplex proteomics 294

High-throughput for proteomics 294

Future directions for protein biochip application 295

Bioinformatics for proteomics 295

High-Throughput Crystallography Consortium 295

Study of protein folding by IBM's Blue Gene 296

Study of proteins by atomic force microscopy 296

Population proteomics 296

Comparative proteome analysis 297

Human Proteome Organization 297

Human Salivary Proteome 298

Academic-commercial collaborations in proteomics 298

Indiana Centers for Applied Protein Sciences 298

Role of proteomics in the healthcare of the future 299

Proteomics and molecular medicine 299

Proteodiagnostics 299

Proteomics and personalized medicine 300

Targeting the ubiquitin pathway for personalized therapy of cancer 300

Protein patterns and personalized medicine 300

Personalizing interferon therapy of hepatitis C virus 302

Protein biochips and personalized medicine 302

Combination of diagnostics and therapeutics 303

Future prospects 303

12. References 305

List of Tables

Table 1 1: Landmarks in the evolution of proteomics 17

Table 1 2: Comparison of DNA and protein 26

Table 1 3: Comparison of mRNA and protein 26

Table 1 4: Methods of analysis at various levels of functional genomics 32

Table 2 1: Proteomics technologies 35

Table 2 2: Protein separation technologies of selected companies 40

Table 2 3: Companies supplying mass spectrometry instruments 42

Table 2 4: Companies involved in cell-based protein assays 64

Table 2 5: Methods used for the study of protein-protein interactions 66

Table 2 6: A selection of companies involved in protein-protein interaction studies 72

Table 2 7: Proteomic technologies used with laser capture microdissection 85

Table 3 1: Applications of protein biochip technology 89

Table 3 2: Selected companies involved in protein biochip/microarray technology 105

Table 4 1: Proteomic databases and other Internet sources of proteomics information 113

Table 4 2: Protein interaction databases available on the Internet 118

Table 4 3: Bioinformatic tools for proteomics from academic sources 123

Table 4 4: Selected companies involved in bioinformatics for proteomics 124

Table 5 1: Applications of proteomics in basic biological research 125

Table 5 2: A sampling of proteomics research projects in academic institutions 140

Table 6 1: Pharmaceutical applications of proteomics 143

Table 6 2: Selected companies relevant to MALDI-MS for drug discovery 151

Table 6 3: Selected companies involved in GPCR-based drug discovery 157

Table 6 4: Companies involved in drug design based on structural proteomics 164

Table 6 5: Proteomic companies with high-throughput protein expression technologies 171

Table 6 6: Selected companies involved in chemogenomics/chemoproteomics 181

Table 6 7: Companies involved in glycoproteomic technologies 186

Table 7 1: Applications of proteomics in human healthcare 199

Table 7 2: Eye disorders and proteomic approaches 227

Table 8 1: Companies involved in applications of proteomics to oncology 249

Table 9 1: Neurodegenerative diseases with underlying protein abnormality 254

Table 9 2: Disease-specific proteins in the cerebrospinal fluid of patients 264

Table 10 1: Potential markets for proteomic technologies 2010-2020 271

Table 10 2: Geographical distribution of markets for proteomic technologies 2010-2020 272

Table 10 3: 2010 revenues of major companies from protein separation technologies 272

Table 11 1: Role of proteomics in personalizing strategies for cancer therapy 300

List of Figures

Figure 1 1: A schematic miRNA pathway 20

Figure 1 2: Relationship of DNA, RNA and protein in the cell 27

Figure 1 3: Protein production pathway from gene expression to functional protein with controls. 29

Figure 1 4: Parallels between functional genomics and proteomics 30

Figure 2 1: Proteomics: flow from sample preparation to characterization 36

Figure 2 2: The central role of spectrometry in proteomics 42

Figure 2 3: Electrospray ionization (ESI) 43

Figure 2 4: Matrix-Assisted Laser Desorption/Ionization (MALDI) 44

Figure 2 5: Scheme of bio-bar-code assay 59

Figure 2 6: A diagrammatic presentation of yeast two-hybrid system 67

Figure 3 1: ProteinChip System 91

Figure 3 2: Surface plasma resonance (SPR) 102

Figure 4 1: Role of bioinformatics in integrating genomic/proteomic-based drug discovery 112

Figure 4 2: Bottom-up and top-down approaches for protein sequencing 121

Figure 6 1: Drug discovery process 144

Figure 6 2: Regulatory changes induced by drugs and implemented at the proteins level. 147

Figure 6 3: Relation of proteome to genome, diseases and drugs 148

Figure 6 4: The mTOR pathways 161

Figure 6 5: Steps in shotgun proteomics 179

Figure 6 6: Chemogenomic approach to drug discovery (3-Dimensional Pharmaceuticals) 180

Figure 8 1: Relation of oncoproteomics to other technologies 231

Figure 9 1: A scheme of proteomics applications in CNS drug discovery and development 270

Figure 10 1: Types of companies involved in proteomics collaborations 279

Figure 10 2: Types of collaborations: R & D, licensing or marketing 280

Figure 10 3: Proteomics collaborations according to application areas 280

Figure 10 4: Proteomics collaborations according to technologies 281

Figure 10 5: Unmet needs in proteomics 286

Figure 11 1: A scheme of the role of proteomics in personalized management of cancer 302

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