Reportlinker Adds Proteomics - Technologies, Markets and Companies

NEW YORK, Nov. 9, 2010 /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

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 218 of these are profiled in the report with 473 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 2009 and are projected to years 2014 and 2019. 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 16

1. Basics of Proteomics .. 18

Introduction . 18

History . 18

Nucleic acids, genes and proteins .. 19

Genome .. 19

DNA . 20

RNA . 20

MicroRNAs .. 20

Decoding of mRNA by the ribosome 21

Genes .. 22

Alternative splicing .. 22

Transcription . 23

Gene regulation 23

Gene expression .. 24

Chromatin .. 24

Proteins .. 25

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

2. Proteomic Technologies 36

Key technologies driving proteomics 36

Sample preparation .. 37

New trends in sample preparation .. 37

Pressure Cycling Technology 38

Protein separation technologies . 38

High resolution 2D gel electrophoresis .. 38

Variations of 2D gel technology .. 39

Limitations of 2DGE and measures to overcome these . 39

1-D sodium dodecyl sulfate (SDS) PAGE .. 39

Capillary electrophoresis systems 40

Head column stacking capillary zone electrophoresis 40

Removal of albumin and IgG 40

Companies with protein separation technologies 41

Protein detection 42

Protein identification and characterization 42

Mass spectrometry (MS) 42

Companies involved in mass spectrometry 43

Electrospray ionization . 44

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 45

Cryogenic MALDI- Fourier Transform Mass Spectrometry . 46

Stable-isotope-dilution tandem mass spectrometry 47

HUPO Gold MS Protein Standard .. 47

High performance liquid chromatography . 47

Multidimensional protein identification technology (MudPIT) .. 47

Peptide mass fingerprinting .. 48

Combination of protein separation technologies with mass spectrometry 48

Combining capillary electrophoresis with mass spectrometry .. 48

2D PAGE and mass spectrometry . 48

Quantification of low abundance proteins .. 49

SDS-PAGE 49

Antibodies and proteomics 50

Detection of fusion proteins .. 50 - 4 -

Labeling and detection of proteins .. 50

Fluorescent labeling of proteins in living cells 51

Combination of microspheres with fluorescence .. 51

Self-labeling protein tags 51

Analysis of peptides 52

C-terminal peptide analysis 52

Differential Peptide Display 53

Peptide analyses using NanoLC-MS . 53

Protein sequencing 54

Real-time PCR for protein quantification. 55

Quantitative proteomics . 55

MS-based quantitative proteomics . 55

MS and cryo-electron tomography .. 55

Functional proteomics: technologies for studying protein function 56

Functional genomics by mass spectrometry . 56

RNA-Protein fusions . 56

Designed repeat proteins 56

Application of nanbiotechnology to proteomics .. 57

Nanoproteomics 57

Protein nanocrystallography .. 57

Single-molecule mass spectrometry using a nanopore .. 58

Nanoelectrospray ionization 58

Nanoparticle barcodes 59

Biobarcode assay for proteins 59

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 .. 70

In vivo study of protein-protein interactions . 71

Computational prediction of interactions 71

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 .. 78

An algorithm for genome-wide prediction of protein function . 79

Monitoring protein function by expression profiling 79

Isotope-coded affinity tag peptide labeling .. 79

Differential Proteomic Panning 80

Cell map proteomics . 80

Topological proteomics 81

Organelle or subcellular proteomics . 82

Nucleolar proteomics 82 - 5 -

Glycoproteomic technologies 82

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 . 90

Introduction . 90

Types of protein biochips 91

ProteinChip 91

Applications and advantages of ProteinChip .. 92

ProteinChip Biomarker System . 92

Matrix-free ProteinChip Array 93

Aptamer-based protein biochip 93

Fluorescence planar wave guide technology-based protein biochips . 94

Lab-on-a-chip for protein analysis .. 94

Microfluidic biochips for proteomics 95

Protein biochips for high-throughput expression. 96

Nucleic Acid-Programmable Protein Array .. 96

High-density protein microarrays . 96

HPLC-Chip for protein identification . 96

Antibody microarrays .. 97

Integration of protein array and image analysis .. 97

Tissue microarray technology for proteomics .. 97

Protein biochips in molecular diagnostics .. 98

A force-based protein biochip .. 99

L1 chip and lipid immobilization .. 99

Multiplexed Protein Profiling on Microarrays . 99

Live cell microarrays .. 100

ProteinArray Workstation 100

Proteome arrays .. 101

The Yeast ProtoArray 101

ProtoArray Human Protein Microarray . 101

TRINECTIN proteome chip .. 102

Peptide arrays .. 102

Surface plasmon resonance technology 103

Biacore's SPR . 103

FLEX CHIP 103

Combination of surface plasmon resonance and MALDI-TOF 104

Protein chips/microarrays using nanotechnology 104

Nanoparticle protein chip 104

Protein nanobiochip .. 104

Protein nanoarrays 105

Self-assembling protein nanoarrays. 105

Companies involved in protein biochip/microarray technology 106

4. Bioinformatics in Relation to Proteomics .. 110

Introduction .. 110

Bioinformatic tools for proteomics .. 110

Testing of SELDI-TOF MS Proteomic Data .. 110

BioImagine's ProteinMine 111

Bioinformatics for pharmaceutical applications of proteomics .. 111

In silico search of drug targets by Biopendium . 111

Compugen's LEADS .. 112

DrugScore 112

Proteochemometric modeling 112

Integration of genomic and proteomic data 113

Proteomic databases: creation and analysis .. 114

Introduction 114

Proteomic databases 114

GenProtEC 115

Human Protein Atlas .. 115 - 6 -

Human Proteomics Initiative 116

International Protein Index.. 116

Proteome maps .. 117

Protein Structure Initiative ? Structural Genomics Knowledgebase . 117

Protein Warehouse Database .. 117

Protein Data Bank .. 117

Universal Protein Resource .. 118

Protein interaction databases 118

Biomolecular Interaction Network Database .. 119

ENCODE .. 119

Functional Genomics Consortium .. 120

Human Proteinpedia .. 120

ProteinCenter .. 120

Databases of the National Center for Biotechnology Information . 121

Bioinformatics for protein identification .. 121

Application of bioinformatics in functional proteomics . 121

Use of bioinformatics in protein sequencing .. 121

Bottom-up protein sequencing .. 122

Top-down protein sequencing 123

Protein structural database approach to drug design 123

Bioinformatics for high-throughput proteomics 123

Companies with bioinformatic tools for proteomics 124

5. Research in Proteomics . 126

Introduction .. 126

Applications of proteomics in biological research 126

Identification of novel human genes by comparative proteomics 126

Study of relationship between genes and proteins .. 127

Characterization of histone codes . 127

Structural genomics or structural proteomics 128

Protein Structure Factory 129

Protein Structure Initiative . 129

Studies on protein structure at Argonne National Laboratory .. 130

Structural Genomics Consortium .. 130

Protein knockout . 131

Antisense approach and proteomics 131

RNAi and protein knockout . 131

Total knockout of cellular proteins 131

Ribozymes and proteomics . 132

Single molecule proteomics 132

Single-molecule photon stamping spectroscopy .. 132

Single nucleotide polymorphism determination by TOF-MS .. 133

Application of proteomic technologies in systems biology .. 133

Signaling pathways and proteomics . 133

Kinomics .. 134

Combinatorial RNAi for quantitative protein network analysis . 134

Proteomics in neuroscience research . 134

Stem cell proteomics . 135

hESC phosphoproteome .. 135

Proteomic studies of mesenchymal stem cells .. 136

Proteomics of neural stem cells . 136

Proteome Biology of Stem Cells Initiative .. 137

Proteomic analysis of the cell cycle 138

Nitric oxide and proteomics 138

A proteomic method for identification of cysteine S-nitrosylation sites . 138

Study of the nitroproteome 138

Study of the phosphoproteome . 139

Study of the mitochondrial proteome 139

Proteomic technologies for study of mitochondrial proteomics 140

Cryptome . 140

Study of protein transport in health and disease . 140

Proteomics research in the academic sector .. 141

Vanderbilt University's Center for Proteomics and Drug Actions . 143

ProteomeBinders initiative.. 143

6. Pharmaceutical Applications of Proteomics . 144

Introduction .. 144

Current drug discovery process and its limitations . 144

Role of omics in drug discovery 145

Genomics-based drug discovery 145

Metabolomics technologies for drug discovery . 146 - 7 -

Role of metabonomics in drug discovery 146

Basis of proteomics approach to drug discovery .. 147

Proteins and drug action .. 147

Transcription-aided drug design . 148

Role of proteomic technologies in drug discovery 148

Liquid chromatography-based drug discovery 149

Capture compound mass spectrometry 150

Protein-expression mapping by 2DGE .. 150

Role of MALDI mass spectrometry in drug discovery 150

Tissue imaging mass spectrometry 150

Companies using MALDI for drug discovery 152

Oxford Genome Anatomy Project . 152

Proteins as drug targets .. 153

Ligands to capture the purine binding proteome . 153

Chemical probes to interrogate key protein families for drug discovery 153

Global proteomics for pharmacodynamics . 154

CellCarta® proteomics platform 154

ZeptoMARK protein profiling system 155

Role of proteomics in targeting disease pathways .. 155

Identification of protein kinases as drug targets .. 155

Mechanisms of action of kinase inhibitors 156

G-protein coupled receptors as drug targets . 156

Methods of study of GPCRs.. 157

Cell-based assays for GPCR . 157

Companies involved in GPCR-based drug discovery . 158

GPCR localization database . 159

Matrix metalloproteases as drug targets 159

PDZ proteins as drug targets . 160

Proteasome as drug target . 160

Serine hydrolases as drug targets 161

Targeting mTOR signaling pathway . 161

Targeting caspase-8 for anticancer therapeutics . 162

Bioinformatic analysis of proteomics data for drug discovery 163

Drug design based on structural proteomics .. 163

Protein crystallography for determining 3D structure of proteins 163

Automated 3D protein modeling .. 164

Drug targeting of flexible dynamic proteins 164

Companies involved in structure-based drug-design .. 164

Integration of genomics and proteomics for drug discovery .. 165

Ligand-receptor binding .. 166

Role of proteomics in study of ligand-receptor binding .. 166

Aptamer protein binding . 167

Systematic Evolution of Ligands by Exponential Enrichment . 167

Aptamers and high-throughput screening 167

Nucleic Acid Biotools.. 168

Aptamer beacons 168

Peptide aptamers 169

Riboreporters for drug discovery . 169

Target identification and validation 169

Application of mass spectrometry for target identification 170

Gene knockout and gene suppression for validating protein targets .. 170

Laser-mediated protein knockout for target validation .. 170

Integrated proteomics for drug discovery .. 171

High-throughput proteomics .. 171

Companies involved in high-throughput proteomics 172

Drug discovery through protein-protein interaction studies .. 172

Protein-protein interaction as basis for drug target identification 173

Protein-PCNA interaction as basis for drug design .. 173

Two-hybrid protein interaction technology for target identification 174

Biosensors for detection of small molecule-protein interactions .. 174

Protein-protein interaction maps .. 175

ProNet (Myriad Genetics) . 175

Hybrigenics' maps of protein-protein interactions . 175

CellZome's functional map of protein-protein interactions . 176

Mapping of protein-protein interactions by mass spectrometry 176

Protein interaction map of Drosophila melanogaster .. 177

Protein-interaction map of Wellcome Trust Sanger Institute 177

Protein-protein interactions as targets for therapeutic intervention 177

Inhibition of protein-protein interactions by peptide aptamers 178

Selective disruption of proteins by small molecules 178

Post-genomic combinatorial biology approach . 178 - 8 -

Differential proteomics . 179

Shotgun proteomics 179

Chemogenomics/chemoproteomics for drug discovery 180

Chemoproteomics-based drug discovery . 181

Companies involved in chemogenomics/chemoproteomics 182

Activity-based proteomics 183

Locus Discovery technology . 183

Automated ligand identification system 184

Expression proteomics: protein level quantification .. 184

Role of phage antibody libraries in target discovery .. 185

Analysis of posttranslational modification of proteins by MS . 185

Phosphoproteomics for drug discovery . 186

Application of glycoproteomics for drug discovery . 186

Role of carbohydrates in proteomics 186

Challenges of glycoproteomics .. 187

Companies involved in glycoproteomics . 187

Role of protein microarrays/ biochips for drug discovery 188

Protein microarrays vs DNA microarrays for high-throughput screening .. 188

BIA-MS biochip for protein-protein interactions 188

ProteinChip with Surface Enhanced Neat Desorption .. 189

Protein-domains microarrays . 189

Some limitations of protein biochips 189

Concluding remarks about role of proteomics in drug discovery .. 190

RNA versus protein profiling as guide to drug development .. 190

RNA as drug target .. 190

Combination of RNA and protein profiling .. 191

RNA binding proteins . 192

Toxicoproteomics. 192

Hepatotoxicity 192

Nephrotoxicity 193

Cardiotoxicity . 193

Neurotoxicity .. 194

Protein/peptide therapeutics . 194

Peptide-based drugs . 194

Phylomer® peptides .. 195

Cryptein-based therapeutics .. 195

Synthetic proteins and peptides as pharmaceuticals .. 196

Genetic immunization and proteomics .. 196

Proteomics and gene therapy 197

Role of proteomics in clinical drug development .. 197

Pharmacoproteomics 197

Role of proteomics in clinical drug safety 198

7. Application of Proteomics in Human Healthcare 200

Introduction .. 200

Clinical proteomics . 201

Definition and standards . 201

Vermillion's Clinical Proteomics Program 201

Pathophysiology of human diseases .. 202

Diseases due to misfolding of proteins 202

Mechanism of protein folding .. 203

Nanoproteomics for study of misfolded proteins 204

Therapies for protein misfolding . 204

Intermediate filament proteins . 205

Significance of mitochondrial proteome in human disease 206

Proteome of Saccharomyces cerevisiae mitochondria .. 206

Rat mitochondrial proteome 206

Proteomic approaches to biomarker identification .. 207

The ideal biomarker . 207

Proteomic technologies for biomarker discovery .. 207

MALDI mass spectrometry for biomarker discovery . 208

BAMF Technology 208

Protein biochips/microarrays and biomarkers .. 209

Antibody-based biomarker discovery .. 209

Tumor-specific serum peptidome patterns . 209

Search for protein biomarkers in body fluids . 210

Challenges and strategies for discovery of protein biomarkers in plasma .. 210

3-D structure of CD38 as a biomarker . 211

BD™ Free Flow Electrophoresis System .. 211

Isotope tags for relative and absolute quantification 212

N-terminal peptide isolation from human plasma . 212 - 9 -

Plasma protein microparticles as biomarkers . 212

Proteome partitioning 213

SISCAPA method for quantitating proteins and peptides in plasma . 213

Stable isotope tagging methods . 213

Technology to measure both the identity and size of the biomarker 214

Biomarkers in the urinary proteome 214

Application of proteomics in molecular diagnosis 215

Proximity ligation assay .. 216

Protein patterns . 216

Proteomic tests on body fluids .. 216

Cyclical amplification of proteins .. 218

Applications of proteomics in infections .. 218

Mass spectrometry for microbial identification . 218

Role of proteomics in virology 219

Study of interaction of proteins with viruses .. 219

Role of proteomics in bacteriology 219

Epidemiology of bacterial infections .. 220

Proteomic approach to bacterial pathogenesis .. 220

Vaccines for bacterial infections . 220

Protein profiles associated with bacterial drug resistance .. 221

Analyses of the parasite proteome .. 221

Application of proteomics in cystic fibrosis . 222

Proteomics of cardiovascular diseases . 222

Pathomechanism of cardiovascular diseases . 222

Study of cardiac mitochondrial proteome in myocardial ischemia .. 222

Cardiac protein databases .. 223

Proteomics of dilated cardiomyopathy and heart failure 223

Proteomic biomarkers of cardiovascular diseases 224

Role of proteomics in cardioprotection 224

Role of proteomics in heart transplantation .. 224

Future of application of proteomics in cardiology . 225

Proteomic technologies for research in pulmonary disorders 225

Application of proteomics in renal disorders .. 226

Diagnosis of renal disorders .. 226

Proteomic biomarkers of acute kidney injury 227

Cystatin C as biomarker of glomerular filtration rate .. 227

Protein biomarkers of nephritis . 227

Proteomics and kidney stones 228

Proteomics of eye disorders 228

Proteomics of cataract . 228

Proteomics of diabetic retinopathy .. 229

Retinal dystrophies .. 229

Use of proteomics in inner ear disorders . 230

Use of proteomics in aging research .. 230

Removal of altered cellular proteins in aging 231

Alteration of glycoproteins during aging . 231

Proteomics and nutrition . 231

8. Oncoproteomics . 232

Introduction .. 232

Proteomic technologies for study of cancer 233

Application of CellCarta technology for oncology . 233

Accentuation of differentially expressed proteins using phage technology 233

Identification of oncogenic tyrosine kinases using phosphoproteomics . 233

Single-cell protein expression analysis by microfluidic techniques.. 234

Dynamic cell proteomics in response to a drug . 234

Desorption electrospray ionization for cancer diagnosis . 234

Proteomic analysis of cancer cell mitochondria . 235

Mass spectrometry for identification of oncogenic chimeric proteins .. 235

Id proteins as targets for cancer therapy .. 236

Proteomic study of p53 236

Human Tumor Gene Index . 236

Integration of cancer genomics and proteomics .. 237

Laser capture microdissection technology and cancer proteomics .. 237

Cancer tissue proteomics 238

Use of proteomics in cancers of various organ systems 238

Proteomics of brain tumors 238

Proteomics of breast cancer .. 239

Proteomics of colorectal cancer . 240

Proteomics of esophageal cancer . 241

Proteomics of hepatic cancer . 241 - 10 -

Proteomics of leukemia 241

Proteomics of lung cancer .. 242

Proteomics of pancreatic cancer 242

Proteomics of prostate cancer 243

Diagnostic use of cancer biomarkers . 244

Proteomic technologies for tumor biomarkers .. 244

Nuclear matrix proteins (NMPs) 245

Antiannexins as tumor markers in lung cancer . 245

NCI's Network of Clinical Proteomic Technology Centers . 246

Proteomics and tumor immunology 247

Proteomics and study of tumor invasiveness . 247

Anticancer drug discovery and development . 247

Kinase-targeted drug discovery in oncology.. 248

Anticancer drug targeting: functional proteomics screen of proteases .. 249

Small molecule inhibitors of cancer-related proteins .. 249

Role of proteomics in studying drug resistance in cancer .. 249

Future prospects of oncoproteomics .. 250

Companies involved in application of proteomics to oncology .. 250

9. Neuroproteomics .. 252

Introduction 252

Proteomics of prion diseases . 252

Transmissible spongiform encephalopathies . 253

Creutzfeld-Jakob disease . 253

Bovine spongiform encephalopathy .. 253

Variant Creutzfeldt-Jakob disease . 254

Protein misfolding and neurodegenerative disorders . 254

Ion channel link for protein-misfolding disease 254

Detection of misfolded proteins . 254

Neurodegenerative disorders with protein abnormalities .. 255

Alzheimer disease .. 257

Common denominators of Alzheimer and prion diseases 257

Parkinson disease .. 258

Amyotrophic lateral sclerosis .. 258

Proteomics and glutamate repeat disorders .. 259

Proteomics and Huntington's disease 259

Proteomics and demyelinating diseases .. 260

Proteomics of neurogenetic disorders .. 260

Fabry disease . 260

GM1 gangliosidosis 261

Quantitative proteomics and familial hemiplegic migraine 261

Proteomics of spinal muscular atrophy 262

Proteomics of CNS trauma .. 262

Proteomics of traumatic brain injury 262

Chronic traumatic encephalopathy and ALS .. 263

Proteomics of CNS aging .. 263

Protein aggregation as a bimarker of aging .. 263

Neuroproteomics of psychiatric disorders 264

Neuroproteomic of cocaine addiction .. 264

Neurodiagnostics based on proteomics. 265

Disease-specific proteins in the cerebrospinal fluid . 265

Tau proteins . 266

CNS tissue proteomics . 266

Diagnosis of CNS disorders by examination of proteins in urine . 268

Diagnosis of CNS disorders by examination of proteins in the blood.. 268

Serum pNF-H as biomarker of CNS damage .. 269

Proteomics of BBB .. 269

Future prospects of neuroproteomics in neurology . 270

HUPO's Pilot Brain Proteome Project 271

10. Commercial Aspects of Proteomics 272

Introduction .. 272

Potential markets for proteomic technologies .. 272

Geographical distribution of proteomics technologies markets 273

Markets for protein separation technologies . 273

Markets for 2D gel electrophoresis 274

Trends in protein separation technologies and effect on market . 274

Protein biochip markets .. 274

Mass spectrometry markets .. 275

Markets for MALDI for drug discovery . 275

Markets for nuclear magnetic resonance spectroscopy .. 275 - 11 -

Market for structure-based drug design . 276

Bioinformatics markets for proteomics 276

Markets for protein biomarkers . 276

Markets for cell-based protein assays . 276

Business and strategic considerations .. 277

Cost of protein structure determination . 277

Opinion surveys of the scientist consumers of proteomic technologies . 277

Opinions on mass spectrometry . 277

Opinions on bioinformatics and proteomic databases .. 277

Systems for in vivo study of protein-protein interactions 278

Perceptions of the value of protein biochip/microfluidic systems .. 278

Small versus big companies .. 278

Expansion in proteomics according to area of application . 278

Growth trends in cell-based protein assay market .. 279

Challenges for development of cell-based protein assays .. 279

Future trends and prospects of cell-based protein assays .. 279

Strategic collaborations .. 280

Analysis of proteomics collaborations according to types of companies . 280

Types of proteomic collaborations . 281

Proteomics collaborations according to application areas 281

Analysis of proteomics collaborations: types of technologies . 281

Collaborations based on protein biochip technology . 282

Concluding remarks about proteomic collaborations 282

Proteomic patents . 283

Market drivers in proteomics . 283

Needs of the pharmaceutical industry . 283

Need for outsourcing proteomic technologies 284

Funding of proteomic companies and research . 284

Technical advances in proteomics 284

Changing trends in healthcare in future . 285

Challenges facing proteomics 285

Magnitude and complexity of the task. 285

Technical challenges . 285

Limitations of proteomics 286

Limitations of 2DGE 286

Limitations of mass spectrometry techniques . 286

Complexity of the pharmaceutical proteomics 286

Unmet needs in proteomics 287

11. Future of Proteomics 288

Genomics to proteomics .. 288

Faster technologies .. 288

FLEXGene repository 288

Need for new proteomic technologies 289

Emerging proteomic technologies 290

Detection of alternative protein isoforms 290

Direct protein identification in large genomes by mass spectrometry 290

Proteome identification kits with stacked membranes 290

Vacuum deposition interface.. 291

In vitro protein biosynthesis .. 291

Proteome mining with adenosine triphosphate . 291

Proteome-scale purification of human proteins from bacteria .. 291

Proteostasis network 292

Cytoproteomics . 292

Subcellular proteomics.. 292

Individual cell proteomics . 293

Live cell proteomics 293

Fluorescent proteins for live-cell imaging 294

Membrane proteomics . 294

Identification of membrane proteins by tandem MS of protein ions . 294

Solid state NMR for study of nanocrystalline membrane proteins . 295

Multiplex proteomics 295

High-throughput for proteomics 295

Future directions for protein biochip application .. 296

Bioinformatics for proteomics 296

High-Throughput Crystallography Consortium .. 296

Study of protein folding by IBM's Blue Gene . 297

Study of proteins by atomic force microscopy .. 297

Population proteomics .. 297

Comparative proteome analysis 298

Human Proteome Organization . 298 - 12 -

Human Salivary Proteome .. 299

Academic-commercial collaborations in proteomics .. 299

Indiana Centers for Applied Protein Sciences 299

Role of proteomics in the healthcare of the future .. 300

Proteomics and molecular medicine . 300

Proteodiagnostics .. 300

Proteomics and personalized medicine 301

Targeting the ubiquitin pathway for personalized therapy of cancer 301

Protein patterns and personalized medicine 301

Personalizing interferon therapy of hepatitis C virus 303

Protein biochips and personalized medicine 303

Combination of diagnostics and therapeutics . 304

Future prospects . 304

12. References . 306

Tables

Table 1-1: Landmarks in the evolution of proteomics 18

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 . 36

Table 2-2: Protein separation technologies of selected companies . 41

Table 2-3: Companies supplying mass spectrometry instruments . 43

Table 2-4: Companies involved in cell-based protein assays 65

Table 2-5: Methods used for the study of protein-protein interactions . 67

Table 2-6: A selection of companies involved in protein-protein interaction studies . 73

Table 2-7: Proteomic technologies used with laser capture microdissection 86

Table 3-1: Applications of protein biochip technology .. 90

Table 3-2: Selected companies involved in protein biochip/microarray technology 106

Table 4-1: Proteomic databases and other Internet sources of proteomics information 114

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

Table 4-3: Bioinformatic tools for proteomics from academic sources 124

Table 4-4: Selected companies involved in bioinformatics for proteomics . 125

Table 5-1: Applications of proteomics in basic biological research .. 126

Table 5-2: A sampling of proteomics research projects in academic institutions . 141

Table 6-1: Pharmaceutical applications of proteomics . 144

Table 6-2: Selected companies relevant to MALDI-MS for drug discovery . 152

Table 6-3: Selected companies involved in GPCR-based drug discovery 158

Table 6-4: Companies involved in drug design based on structural proteomics .. 165

Table 6-5: Proteomic companies with high-throughput protein expression technologies .. 172

Table 6-6: Selected companies involved in chemogenomics/chemoproteomics .. 182

Table 6-7: Companies involved in glycoproteomic technologies .. 187

Table 7-1: Applications of proteomics in human healthcare .. 200

Table 7-2: Eye disorders and proteomic approaches 228

Table 8-1: Companies involved in applications of proteomics to oncology 250

Table 9-1: Neurodegenerative diseases with underlying protein abnormality .. 255

Table 9-2: Disease-specific proteins in the cerebrospinal fluid of patients . 265

Table 10-1: Potential markets for proteomic technologies 2009-2019 272

Table 10-2: Geographical distribution of markets for proteomic technologies 2009-2019 273

Table 10-3: 2009 revenues of major companies from protein separation technologies . 273

Table 11-1: Role of proteomics in personalizing strategies for cancer therapy 301

Figures

Figure 1-1: A schematic miRNA pathway .. 21

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 functions

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