Reportlinker Adds Proteomics - Technologies, Markets and Companies

Jun 03, 2010, 12:24 ET from Reportlinker

NEW YORK, June 3 /PRNewswire/ -- announces that a new market research report is available in its catalogue:

Proteomics - Technologies, Markets and Companies


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. The text is supplemented with 42 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 468 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


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 20

Alternative splicing 20

Transcription 21

Gene regulation 22

Gene expression 22

Chromatin 23

Proteins 23

Spliceosome 23

Functions of proteins 24

Inter-relationship of protein, mRNA and DNA 24

Proteomics 25

Mitochondrial proteome 26

S-nitrosoproteins in mitochondria 27

Proteomics and genomics 27

Classification of proteomics 30

Levels of functional genomics and various "omics" 30

Glycoproteomics 30

Transcriptomics 31

Metabolomics 31

Cytomics 31

Phenomics 31

Proteomics and systems biology 32

2. Proteomic Technologies 33

Key technologies driving proteomics 33

Sample preparation 34

New trends in sample preparation 34

Pressure Cycling Technology 35

Protein separation technologies 35

High resolution 2D gel electrophoresis 35

Variations of 2D gel technology 36

Limitations of 2DGE and measures to overcome these 36

1-D sodium dodecyl sulfate (SDS) PAGE 36

Capillary electrophoresis systems 37

Head column stacking capillary zone electrophoresis 37

Removal of albumin and IgG 37

Companies with protein separation technologies 38

Protein detection 39

Protein identification and characterization 39

Mass spectrometry (MS) 39

Companies involved in mass spectrometry 40

Electrospray ionization 41

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 42

Cryogenic MALDI- Fourier Transform Mass Spectrometry 43

Stable-isotope-dilution tandem mass spectrometry 44

HUPO Gold MS Protein Standard 44

High performance liquid chromatography 44

Multidimensional protein identification technology (MudPIT) 44

Peptide mass fingerprinting 45

Combination of protein separation technologies with mass spectrometry 45

Combining capillary electrophoresis with mass spectrometry 45

2D PAGE and mass spectrometry 45

Quantification of low abundance proteins 46


Antibodies and proteomics 47

Detection of fusion proteins 47

Labeling and detection of proteins 47

Fluorescent labeling of proteins in living cells 48

Combination of microspheres with fluorescence 48

Self-labeling protein tags 48

Analysis of peptides 49

Differential Peptide Display 49

Peptide analyses using NanoLC-MS 50

Protein sequencing 51

Real-time PCR for protein quantification 51

Quantitative proteomics 52

MS-based quantitative proteomics 52

MS and cryo-electron tomography 52

Functional proteomics: technologies for studying protein function 52

Functional genomics by mass spectrometry 53

RNA-Protein fusions 53

Designed repeat proteins 53

Application of nanbiotechnology to proteomics 54

Nanoproteomics 54

Protein nanocrystallography 54

Single-molecule mass spectrometry using a nanopore 55

Nanoelectrospray ionization 55

Nanoparticle barcodes 55

Biobarcode assay for proteins 56

Nanobiotechnology for discovery of protein biomarkers in the blood 57

Nanoscale protein analysis 57

Nanoscale mechanism for protein engineering 58

Nanotube electronic biosensor 58

Nanotube-vesicle networks for study of membrane proteins 59

Nanowire transistor for the detection of protein-protein interactions 59

Qdot-nanocrystals 59

Resonance Light Scattering technology 60

Study of single membrane proteins at subnanometer resolution 60

Protein expression profiling 60

Cell-based protein assays 61

Living cell-based assays for protein function 62

Companies developing cell-based protein assays 62

Protein function studies 63

Transcriptionally Active PCR 63

Protein-protein interactions 63

Yeast two-hybrid system 65

Membrane one-hybrid method 66

Protein affinity chromatography 66

Phage display 67

Fluorescence Resonance Energy Transfer 67

Bioluminescence Resonance Energy Transfer 67

Detection Enhanced Ubiquitin Split Protein Sensor technology 67

Protein-fragment complementation system 68

In vivo study of protein-protein interactions 68

Computational prediction of interactions 69

Interactome 69

Protein-protein interactions and drug discovery 70

Companies with technologies for protein-protein interaction studies 70

Protein-DNA interaction 71

Determination of protein structure 72

X-Ray crystallography 72

Nuclear magnetic resonance 73

Electron spin resonance 73

Prediction of protein structure 74

Protein tomography 74

X-ray scattering-based method for determining the structure of proteins 75

Prediction of protein function 75

Three-dimensional proteomics for determination of function 76

An algorithm for genome-wide prediction of protein function 76

Monitoring protein function by expression profiling 76

Isotope-coded affinity tag peptide labeling 77

Differential Proteomic Panning 77

Cell map proteomics 78

Topological proteomics 78

Organelle or subcellular proteomics 79

Nucleolar proteomics 79

Glycoproteomic technologies 80

High-sensitivity glycoprotein analysis 80

Fluorescent in vivo imaging of glycoproteins 80

Integrated approaches for protein characterization 80

Imaging mass spectrometry 81

IMS technologies 81

Applications of IMS 82

The protein microscope 82

Automation and robotics in proteomics 82

Laser capture microdissection 83

Microdissection techniques used for proteomics 83

Uses of LCM in combination with proteomic technologies 83

Concluding remarks about applications of proteomic technologies 84

Precision proteomics 85

3. Protein biochip technology 87

Introduction 87

Types of protein biochips 88

ProteinChip 88

Applications and advantages of ProteinChip 89

ProteinChip Biomarker System 89

Matrix-free ProteinChip Array 90

Aptamer-based protein biochip 90

Fluorescence planar wave guide technology-based protein biochips 91

Lab-on-a-chip for protein analysis 91

Microfluidic biochips for proteomics 92

Protein biochips for high-throughput expression 93

Nucleic Acid-Programmable Protein Array 93

High-density protein microarrays 93

HPLC-Chip for protein identification 93

Antibody microarrays 94

Integration of protein array and image analysis 94

Tissue microarray technology for proteomics 94

Protein biochips in molecular diagnostics 95

A force-based protein biochip 96

L1 chip and lipid immobilization 96

Multiplexed Protein Profiling on Microarrays 96

Live cell microarrays 97

ProteinArray Workstation 97

Proteome arrays 98

The Yeast ProtoArray 98

ProtoArray Human Protein Microarray 98

TRINECTIN proteome chip 99

Peptide arrays 99

Surface plasmon resonance technology 100

Biacore's SPR 100


Combination of surface plasmon resonance and MALDI-TOF 101

Protein chips/microarrays using nanotechnology 101

Nanoparticle protein chip 101

Protein nanobiochip 101

Protein nanoarrays 102

Self-assembling protein nanoarrays 102

Companies involved in protein biochip/microarray technology 103

4. Bioinformatics in Relation to Proteomics 107

Introduction 107

Bioinformatic tools for proteomics 107

Testing of SELDI-TOF MS Proteomic Data 107

BioImagine's ProteinMine 108

Bioinformatics for pharmaceutical applications of proteomics 108

In silico search of drug targets by Biopendium 108

Compugen's LEADS 109

DrugScore 109

Proteochemometric modeling 109

Integration of genomic and proteomic data 110

Proteomic databases: creation and analysis 111

Introduction 111

Proteomic databases 111

GenProtEC 112

Human Protein Atlas 112

Human Proteomics Initiative 113

International Protein Index 113

Proteome maps 114

Protein Structure Initiative ? Structural Genomics Knowledgebase 114

Protein Warehouse Database 114

Protein Data Bank 114

Universal Protein Resource 115

Protein interaction databases 115

Biomolecular Interaction Network Database 116


Functional Genomics Consortium 117

Human Proteinpedia 117

ProteinCenter 117

Databases of the National Center for Biotechnology Information 118

Bioinformatics for protein identification 118

Application of bioinformatics in functional proteomics 118

Use of bioinformatics in protein sequencing 118

Bottom-up protein sequencing 119

Top-down protein sequencing 120

Protein structural database approach to drug design 120

Bioinformatics for high-throughput proteomics 120

Companies with bioinformatic tools for proteomics 121

5. Research in Proteomics 123

Introduction 123

Applications of proteomics in biological research 123

Identification of novel human genes by comparative proteomics 123

Study of relationship between genes and proteins 124

Characterization of histone codes 124

Structural genomics or structural proteomics 125

Protein Structure Factory 126

Protein Structure Initiative 126

Studies on protein structure at Argonne National Laboratory 127

Structural Genomics Consortium 127

Protein knockout 128

Antisense approach and proteomics 128

RNAi and protein knockout 128

Total knockout of cellular proteins 128

Ribozymes and proteomics 129

Single molecule proteomics 129

Single-molecule photon stamping spectroscopy 129

Single nucleotide polymorphism determination by TOF-MS 130

Application of proteomic technologies in systems biology 130

Signaling pathways and proteomics 130

Kinomics 131

Combinatorial RNAi for quantitative protein network analysis 131

Proteomics in neuroscience research 131

Stem cell proteomics 132

hESC phosphoproteome 132

Proteomic studies of mesenchymal stem cells 133

Proteomics of neural stem cells 133

Proteome Biology of Stem Cells Initiative 134

Proteomic analysis of the cell cycle 135

Nitric oxide and proteomics 135

A proteomic method for identification of cysteine S-nitrosylation sites 135

Study of the nitroproteome 135

Study of the phosphoproteome 136

Study of the mitochondrial proteome 136

Proteomic technologies for study of mitochondrial proteomics 137

Cryptome 137

Study of protein transport in health and disease 137

Proteomics research in the academic sector 138

Vanderbilt University's Center for Proteomics and Drug Actions 140

ProteomeBinders initiative 140

6. Pharmaceutical Applications of Proteomics 141

Introduction 141

Current drug discovery process and its limitations 141

Role of omics in drug discovery 142

Genomics-based drug discovery 142

Metabolomics technologies for drug discovery 143

Role of metabonomics in drug discovery 143

Basis of proteomics approach to drug discovery 144

Proteins and drug action 144

Transcription-aided drug design 145

Role of proteomic technologies in drug discovery 145

Liquid chromatography-based drug discovery 146

Capture compound mass spectrometry 147

Protein-expression mapping by 2DGE 147

Role of MALDI mass spectrometry in drug discovery 147

Tissue imaging mass spectrometry 147

Companies using MALDI for drug discovery 149

Oxford Genome Anatomy Project 149

Proteins as drug targets 150

Ligands to capture the purine binding proteome 150

Chemical probes to interrogate key protein families for drug discovery 150

Global proteomics for pharmacodynamics 151

CellCarta® proteomics platform 151

ZeptoMARK protein profiling system 152

Role of proteomics in targeting disease pathways 152

Identification of protein kinases as drug targets 152

Mechanisms of action of kinase inhibitors 153

G-protein coupled receptors as drug targets 153

Methods of study of GPCRs 154

Cell-based assays for GPCR 154

Companies involved in GPCR-based drug discovery 155

GPCR localization database 156

Matrix metalloproteases as drug targets 156

PDZ proteins as drug targets 157

Proteasome as drug target 157

Serine hydrolases as drug targets 158

Targeting mTOR signaling pathway 158

Targeting caspase-8 for anticancer therapeutics 159

Bioinformatic analysis of proteomics data for drug discovery 160

Drug design based on structural proteomics 160

Protein crystallography for determining 3D structure of proteins 160

Automated 3D protein modeling 161

Drug targeting of flexible dynamic proteins 161

Companies involved in structure-based drug-design 161

Integration of genomics and proteomics for drug discovery 162

Ligand-receptor binding 163

Role of proteomics in study of ligand-receptor binding 163

Aptamer protein binding 164

Systematic Evolution of Ligands by Exponential Enrichment 164

Aptamers and high-throughput screening 164

Nucleic Acid Biotools 165

Aptamer beacons 165

Peptide aptamers 166

Riboreporters for drug discovery 166

Target identification and validation 166

Application of mass spectrometry for target identification 167

Gene knockout and gene suppression for validating protein targets 167

Laser-mediated protein knockout for target validation 167

Integrated proteomics for drug discovery 168

High-throughput proteomics 168

Companies involved in high-throughput proteomics 169

Drug discovery through protein-protein interaction studies 169

Protein-protein interaction as basis for drug target identification 170

Protein-PCNA interaction as basis for drug design 170

Two-hybrid protein interaction technology for target identification 171

Biosensors for detection of small molecule-protein interactions 171

Protein-protein interaction maps 172

ProNet (Myriad Genetics) 172

Hybrigenics' maps of protein-protein interactions 172

CellZome's functional map of protein-protein interactions 173

Mapping of protein-protein interactions by mass spectrometry 173

Protein interaction map of Drosophila melanogaster 174

Protein-interaction map of Wellcome Trust Sanger Institute 174

Protein-protein interactions as targets for therapeutic intervention 174

Inhibition of protein-protein interactions by peptide aptamers 175

Selective disruption of proteins by small molecules 175

Post-genomic combinatorial biology approach 175

Differential proteomics 176

Shotgun proteomics 176

Chemogenomics/chemoproteomics for drug discovery 177

Chemoproteomics-based drug discovery 178

Companies involved in chemogenomics/chemoproteomics 179

Activity-based proteomics 180

Locus Discovery technology 180

Automated ligand identification system 181

Expression proteomics: protein level quantification 181

Role of phage antibody libraries in target discovery 182

Analysis of posttranslational modification of proteins by MS 182

Phosphoproteomics for drug discovery 183

Application of glycoproteomics for drug discovery 183

Role of carbohydrates in proteomics 183

Challenges of glycoproteomics 184

Companies involved in glycoproteomics 184

Role of protein microarrays/ biochips for drug discovery 185

Protein microarrays vs DNA microarrays for high-throughput screening 185

BIA-MS biochip for protein-protein interactions 185

ProteinChip with Surface Enhanced Neat Desorption 186

Protein-domains microarrays 186

Some limitations of protein biochips 186

Concluding remarks about role of proteomics in drug discovery 187

RNA versus protein profiling as guide to drug development 187

RNA as drug target 187

Combination of RNA and protein profiling 188

RNA binding proteins 189

Toxicoproteomics 189

Hepatotoxicity 189

Nephrotoxicity 190

Cardiotoxicity 190

Neurotoxicity 191

Protein/peptide therapeutics 191

Peptide-based drugs 191

Phylomer® peptides 192

Cryptein-based therapeutics 192

Synthetic proteins and peptides as pharmaceuticals 193

Genetic immunization and proteomics 193

Proteomics and gene therapy 194

Role of proteomics in clinical drug development 194

Pharmacoproteomics 194

Role of proteomics in clinical drug safety 195

7. Application of Proteomics in Human Healthcare 197

Clinical proteomics 198

Definition and standards 198

Vermillion's Clinical Proteomics Program 198

Pathophysiology of human diseases 199

Diseases due to misfolding of proteins 199

Mechanism of protein folding 200

Nanoproteomics for study of misfolded proteins 201

Therapies for protein misfolding 201

Intermediate filament proteins 202

Significance of mitochondrial proteome in human disease 203

Proteome of Saccharomyces cerevisiae mitochondria 203

Rat mitochondrial proteome 203

Proteomic approaches to biomarker identification 204

The ideal biomarker 204

Proteomic technologies for biomarker discovery 204

MALDI mass spectrometry for biomarker discovery 205

BAMF Technology 205

Protein biochips/microarrays and biomarkers 206

Antibody-based biomarker discovery 206

Tumor-specific serum peptidome patterns 206

Search for protein biomarkers in body fluids 207

Challenges and strategies for discovery of protein biomarkers in plasma 207

3-D structure of CD38 as a biomarker 208

BD™ Free Flow Electrophoresis System 208

Isotope tags for relative and absolute quantification 209

N-terminal peptide isolation from human plasma 209

Plasma protein microparticles as biomarkers 209

Proteome partitioning 210

SISCAPA method for quantitating proteins and peptides in plasma 210

Stable isotope tagging methods 210

Technology to measure both the identity and size of the biomarker 211

Biomarkers in the urinary proteome 211

Application of proteomics in molecular diagnosis 212

Proximity ligation assay 213

Protein patterns 213

Proteomic tests on body fluids 213

Cyclical amplification of proteins 215

Applications of proteomics in infections 215

Role of proteomics in virology 215

Study of interaction of proteins with viruses 216

Role of proteomics in bacteriology 216

Epidemiology of bacterial infections 216

Proteomic approach to bacterial pathogenesis 217

Vaccines for bacterial infections 217

Protein profiles associated with bacterial drug resistance 218

Analyses of the parasite proteome 218

Application of proteomics in cystic fibrosis 218

Oncoproteomics 219

Application of CellCarta technology for oncology 221

Accentuation of differentially expressed proteins using phage technology 221

Identification of oncogenic tyrosine kinases using phosphoproteomics 221

Single-cell protein expression analysis by microfluidic techniques 222

Dynamic cell proteomics in response to a drug 222

Desorption electrospray ionization for cancer diagnosis 222

Proteomic analysis of cancer cell mitochondria 222

Mass spectrometry for identification of oncogenic chimeric proteins 223

Id proteins as targets for cancer therapy 223

Proteomic study of p53 224

Human Tumor Gene Index 224

Integration of cancer genomics and proteomics 224

Laser capture microdissection technology and cancer proteomics 225

Cancer tissue proteomics 225

Use of proteomics in cancers of various organ systems 226

Proteomics of brain tumors 226

Proteomics of breast cancer 227

Proteomics of colorectal cancer 228

Proteomics of esophageal cancer 228

Proteomics of hepatic cancer 229

Proteomics of leukemia 229

Proteomics of lung cancer 230

Proteomics of pancreatic cancer 230

Proteomics of prostate cancer 231

Diagnostic use of cancer biomarkers 231

NCI's Network of Clinical Proteomic Technology Centers for Cancer Research 233

Proteomics and tumor immunology 234

Proteomics and study of tumor invasiveness 235

Anticancer drug discovery and development 235

Kinase-targeted drug discovery in oncology 235

Anticancer drug targeting: functional proteomics screen of proteases 236

Small molecule inhibitors of cancer-related proteins 236

Role of proteomics in studying drug resistance in cancer 237

Future prospects of oncoproteomics 237

Companies involved in application of proteomics to oncology 237

Application of proteomics in neurological disorders 238

Neuroproteomics 238

Prion diseases 239

Proteomics and transmissible spongiform encephalopathies 240

Proteomics and neurodegenerative disorders 241

Detection of misfolded proteins 243

Proteomics and glutamate repeat disorders 243

Proteomics and Huntington's disease 243

Proteomics and Parkinson's disease 244

Proteomics and Alzheimer's disease 244

Common denominators of Alzheimer's and prion diseases 245

Ion channel link for protein-misfolding disease 245

Proteomics and demyelinating diseases 246

Proteomics of amyotrophic lateral sclerosis 246

Proteomics of spinal muscular atrophy 247

Proteomics of Fabry disease 247

Proteomics and GM1 gangliosidosis 247

Proteomics of CNS trauma 248

Proteomics of CNS aging 249

Neuroproteomics of psychiatric disorders 249

Neuroproteomic of cocaine addiction 250

Neurodiagnostics based on proteomics 250

Testing for disease-specific proteins in the cerebrospinal fluid 250

Tau proteins 251

CNS tissue proteomics 252

Diagnosis of CNS disorders by examination of proteins in urine 253

Diagnosis of CNS disorders by examination of proteins in the blood 253

Serum pNF-H as biomarker of CNS damage 254

Proteomics of BBB 255

Future prospects of neuroproteomics in neurology 255

HUPO's Pilot Brain Proteome Project 256

Proteomics of cardiac disorders 256

Study of cardiac mitochondrial proteome in myocardial ischemia 257

Cardiac protein databases 257

Proteomics of dilated cardiomyopathy and heart failure 257

Role of proteomics in heart transplantation 258

Future of application of proteomics in cardiology 258

Proteomic technologies for research in pulmonary disorders 258

Application for proteomics in renal disorders 260

Diagnosis of renal disorders 260

Proteomic biomarkers of acute kidney injury 260

Cystatin C as biomarker of glomerular filtration rate 260

Protein biomarkers of nephritis 261

Proteomics and kidney stones 261

Proteomics of eye disorders 261

Retinal dystrophies 262

Use of proteomics in inner ear disorders 262

Use of proteomics in aging research 263

Removal of altered cellular proteins in aging 263

Proteomics and nutrition 264

8. Commercial Aspects of Proteomics 265

Introduction 265

Potential markets for proteomic technologies 265

Geographical distribution of proteomics technologies markets 266

Markets for protein separation technologies 266

Markets for 2D gel electrophoresis 267

Trends in protein separation technologies and effect on market 267

Protein biochip markets 267

Mass spectrometry markets 268

Markets for MALDI for drug discovery 268

Markets for nuclear magnetic resonance spectroscopy 268

Market for structure-based drug design 269

Bioinformatics markets for proteomics 269

Markets for protein biomarkers 269

Markets for cell-based protein assays 269

Business and strategic considerations 270

Cost of protein structure determination 270

Opinion surveys of the scientist consumers of proteomic technologies 270

Opinions on mass spectrometry 270

Opinions on bioinformatics and proteomic databases 270

Systems for in vivo study of protein-protein interactions 271

Perceptions of the value of protein biochip/microfluidic systems 271

Small versus big companies 271

Expansion in proteomics according to area of application 271

Growth trends in cell-based protein assay market 272

Challenges for development of cell-based protein assays 272

Future trends and prospects of cell-based protein assays 272

Strategic collaborations 273

Analysis of proteomics collaborations according to types of companies 273

Types of proteomic collaborations 274

Proteomics collaborations according to application areas 274

Analysis of proteomics collaborations: types of technologies 274

Collaborations based on protein biochip technology 275

Concluding remarks about proteomic collaborations 275

Proteomic patents 276

Market drivers in proteomics 276

Needs of the pharmaceutical industry 276

Need for outsourcing proteomic technologies 277

Funding of proteomic companies and research 277

Technical advances in proteomics 277

Changing trends in healthcare in future 278

Challenges facing proteomics 278

Magnitude and complexity of the task 278

Technical challenges 278

Limitations of proteomics 279

Limitations of 2DGE 279

Limitations of mass spectrometry techniques 279

Complexity of the pharmaceutical proteomics 279

Unmet needs in proteomics 280

9. Future of Proteomics 281

Genomics to proteomics 281

Faster technologies 281

FLEXGene repository 281

Need for new proteomic technologies 282

Emerging proteomic technologies 283

Detection of alternative protein isoforms 283

Direct protein identification in large genomes by mass spectrometry 283

Proteome identification kits with stacked membranes 283

Vacuum deposition interface 284

In vitro protein biosynthesis 284

Proteome mining with adenosine triphosphate 284

Proteome-scale purification of human proteins from bacteria 284

Proteostasis network 285

Cytoproteomics 285

Subcellular proteomics 285

Individual cell proteomics 286

Live cell proteomics 286

Fluorescent proteins for live-cell imaging 287

Membrane proteomics 287

Identification of membrane proteins by tandem MS of protein ions 287

Solid state NMR for study of nanocrystalline membrane proteins 288

Multiplex proteomics 288

High-throughput for proteomics 288

Future directions for protein biochip application 289

Bioinformatics for proteomics 289

High-Throughput Crystallography Consortium 289

Study of protein folding by IBM's Blue Gene 290

Study of proteins by atomic force microscopy 290

Population proteomics 290

Comparative proteome analysis 291

Human Proteome Organization 291

Human Salivary Proteome 292

Academic-commercial collaborations in proteomics 292

Indiana Centers for Applied Protein Sciences 292

Role of proteomics in the healthcare of the future 293

Proteomics and molecular medicine 293

Proteodiagnostics 293

Proteomics and personalized medicine 294

Targeting the ubiquitin pathway for personalized therapy of cancer 294

Protein patterns and personalized medicine 294

Personalizing interferon therapy of hepatitis C virus 296

Protein biochips and personalized medicine 296

Combination of diagnostics and therapeutics 297

Future prospects 297

10. References 299


Table 1 1: Landmarks in the evolution of proteomics 17

Table 1 2: Comparison of DNA and protein 24

Table 1 3: Comparison of mRNA and protein 25

Table 1 4: Methods of analysis at various levels of functional genomics 30

Table 2 1: Proteomics technologies 33

Table 2 2: Protein separation technologies of selected companies 38

Table 2 3: Companies supplying mass spectrometry instruments 40

Table 2 4: Companies involved in cell-based protein assays 62

Table 2 5: Methods used for the study of protein-protein interactions 64

Table 2 6: A selection of companies involved in protein-protein interaction studies 70

Table 2 7: Proteomic technologies used with laser capture microdissection 84

Table 3 1: Applications of protein biochip technology 87

Table 3 2: Selected companies involved in protein biochip/microarray technology 103

Table 4 1: Proteomic databases and other Internet sources of proteomics information 111

Table 4 2: Protein interaction databases available on the Internet 115

Table 4 3: Bioinformatic tools for proteomics from academic sources 121

Table 4 4: Selected companies involved in bioinformatics for proteomics 122

Table 5 1: Applications of proteomics in basic biological research 123

Table 5 2: A sampling of proteomics research projects in academic institutions 138

Table 6 1: Pharmaceutical applications of proteomics 141

Table 6 2: Selected companies relevant to MALDI-MS for drug discovery 149

Table 6 3: Selected companies involved in GPCR-based drug discovery 155

Table 6 4: Companies involved in drug design based on structural proteomics 162

Table 6 5: Proteomic companies with high-throughput protein expression technologies 169

Table 6 6: Selected companies involved in chemogenomics/chemoproteomics 179

Table 6 7: Companies involved in glycoproteomic technologies 184

Table 7 1: Applications of proteomics in human healthcare 197

Table 7 2: Companies involved in applications of proteomics to oncology 236

Table 7 3: Neurodegenerative diseases with underlying protein abnormality 240

Table 7 4: Disease-specific proteins in the cerebrospinal fluid of patients 249

Table 7 5: Eye disorders and proteomic approaches 261

Table 8 1: Potential markets for proteomic technologies 2009-2019 265

Table 8 2: Geographical distribution of markets for proteomic technologies 2009-2019 266

Table 8 3: 2009 revenues of major companies from protein separation technologies 266

Table 9 1: Role of proteomics in personalizing strategies for cancer therapy 294


Figure 1 1: Relationship of DNA, RNA and protein in the cell 25

Figure 1 2: Protein production pathway from gene expression to functional protein with controls. 28

Figure 1 3: Parallels between functional genomics and proteomics 28

Figure 2 1: Proteomics: flow from sample preparation to characterization 34

Figure 2 2: The central role of spectrometry in proteomics 40

Figure 2 3: Electrospray ionization (ESI) 41

Figure 2 4: Matrix-Assisted Laser Desorption/Ionization (MALDI) 42

Figure 2 5: Scheme of bio-bar-code assay 57

Figure 2 6: A diagrammatic presentation of yeast two-hybrid system 65

Figure 3 1: ProteinChip System 89

Figure 3 2: Surface plasma resonance (SPR) 100

Figure 4 1: Role of bioinformatics in integrating genomic/proteomic-based drug discovery 110

Figure 4 2: Bottom-up and top-down approaches for protein sequencing 119

Figure 6 1: Drug discovery process 142

Figure 6 2: Regulatory changes induced by drugs and implemented at the proteins level. 145

Figure 6 3: Relation of proteome to genome, diseases and drugs 146

Figure 6 4: The mTOR pathways 159

Figure 6 5: Steps in shotgun proteomics 177

Figure 6 6: Chemogenomic approach to drug discovery (3-Dimensional Pharmaceuticals) 178

Figure 7 1: Relation of oncoproteomics to other technologies 219

Figure 7 2: A scheme of proteomics applications in CNS drug discovery and development 255

Figure 8 1: Types of companies involved in proteomics collaborations 273

Figure 8 2: Types of collaborations: R & D, licensing or marketing 274

Figure 8 3: Proteomics collaborations according to application areas 274

Figure 8 4: Proteomics collaborations according to technologies 275

Figure 8 5: Unmet needs in proteomics 280

Figure 9 1: A scheme of the role of proteomics in personalized management of cancer 296

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