Proteomics - Technologies, Markets and Companies |
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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 ...29 Levels of functional genomics and various "omics" ........30 Glycoproteomics 30 Transcriptomics 30 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 Protein separation technologies.............. 35 High resolution 2D gel electrophoresis ......35 Variations of 2D gel technology................35 Limitations of 2DGE and measures to overcome these ...36 1-D sodium dodecyl sulfate (SDS) PAGE ...36 Capillary electrophoresis systems.............36 Head column stacking capillary zone electrophoresis .....37 Removal of albumin and IgG..37 Companies with protein separation technologies ...........37 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 HUPO Gold MS Protein Standard..........43 High performance liquid chromatography ..44 Multidimensional protein identification technology (MudPIT) .............44 Peptide mass fingerprinting ...44 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 ................45 Antibodies and proteomics ....46 Labeling and detection of proteins ............46 Fluorescent labeling of proteins in living cells ...........46 Combination of microspheres with fluorescence .......47 Self-labeling protein tags .47 - 4 - Analysis of peptides..............47 Differential Peptide Display.................48 Peptide analyses using NanoLC-MS......49 Protein sequencing ...............50 Functional proteomics: technologies for studying protein function................. 50 RNA-Protein fusions.............. 50 Designed repeat proteins...... 51 Application of nanbiotechnology to proteomics.......... 51 Nanoproteomics51 Protein nanocrystallography ...............52 Single-molecule mass spectrometry using a nanopore ................52 Nanoelectrospray ionization................52 Nanoparticle barcodes ..........53 Biobarcode assay for proteins .............53 Resonance Light Scattering technology .....55 Nanoscale protein analysis ....55 Nanobiotechnology for discovery of protein biomarkers in the blood ..55 Study of single membrane proteins at subnanometer resolution........56 Nanotube-vesicle networks for study of membrane proteins .............56 Qdot-nanocrystals................57 Nanotube electronic biosensor .................57 A nanoscale mechanism for protein engineering............57 Protein expression profiling .. 58 Protein function studies ........ 58 Transcriptionally Active PCR ..58 Cell-based protein function assays ...........59 Protein-protein interactions ...59 Yeast two-hybrid system..61 Membrane one-hybrid method ............62 Protein affinity chromatography ..........62 Phage display .................62 Fluorescence Resonance Energy Transfer ................63 Bioluminescence Resonance Energy Transfer ...........63 Detection Enhanced Ubiquitin Split Protein Sensor technology......64 Protein-fragment complementation system..............64 In vivo study of protein-protein interactions ............64 Computational prediction of interactions .................65 Interactome 65 Protein-protein interactions and drug discovery........66 Companies with technologies for protein-protein interaction studies ................66 Protein-DNA interaction ........67 Determination of protein structure ...........67 X-Ray crystallography...........68 Nuclear magnetic resonance..69 Electron spin resonance ...69 Prediction of protein structure70 Protein tomography ..............70 Prediction of protein function .71 Three-dimensional proteomics for determination of function ........71 An algorithm for genome-wide prediction of protein function .......72 Monitoring protein function by expression profiling ...72 Isotope-coded affinity tag peptide labeling................ 72 Differential Proteomic Panning ............... 73 Cell map proteomics.............. 73 Topological proteomics ......... 73 Organelle or subcellular proteomics........ 74 Nucleolar proteomics ............ 75 Glycoproteomic technologies 75 High-sensitivity glycoprotein analysis........75 Fluorescent in vivo imaging of glycoproteins.................75 Integrated approaches for protein characterization... 76 Imaging mass spectrometry ..76 The protein microscope.........77 Automation and robotics in proteomics... 77 Laser capture microdissection ................ 78 Microdissection techniques used for proteomics ............78 Uses of LCM in combination with proteomic technologies78 Concluding remarks about applications of proteomic technologies................. 79 3. Protein biochip technology ............ 81 Introduction...... 81 - 5 - Types of protein biochips ...... 82 ProteinChip ......82 Applications and advantages of ProteinChip .............83 ProteinChip Biomarker System............83 Matrix-free ProteinChip Array..............84 Lab-on-a-chip for protein analysis ............84 Protein biochips based on fluorescence planar wave guide technology85 Application of microfluidic biochips in proteomics ..........85 Aptamer-based protein biochip ................86 High-density protein microarrays .............86 Protein biochips with a functional continuum.................87 Tissue microarray technology for proteomics ............ 87 Protein biochips for high-throughput expression....... 88 Antibody microarrays............89 Protein biochips in molecular diagnostics 89 A force-based protein biochip 90 L1 chip and lipid immobilization ...............90 Multiplexed Protein Profiling on Microarrays90 Live cell microarrays ............. 91 ProteinArray Workstation ..... 91 Proteome arrays 92 The Yeast ProtoArray............92 ProtoArray Ô Human Protein Microarray.....92TRINECTIN proteome chip.....93 Peptide arrays.... 93 Surface plasmon resonance technology .. 94 Biacore's SPR ...94 FLEX CHIP........94 Combination of surface plasmon resonance and MALDI-TOF .............95 Protein chips/microarrays using nanotechnology...... 95 Nanoparticle protein chip ......95 Protein nanobiochip ..............96 Protein nanoarrays ...............96 Self-assembling protein nanoarrays..........96 Companies involved in protein biochip/microarray technology.... 97 4. Bioinformatics in Relation to Proteomics ....... 101 Introduction.... 101 Bioinformatic tools for proteomics........ 101 Testing of SELDI-TOF MS Proteomic Data 101 BioImagine’s ProteinMine .... 102 Bioinformatics for pharmaceutical applications of proteomics ... 102 In silico search of drug targets by Biopendium ............ 102 Compugen's LEADS ............ 103 DrugScore...... 103 Proteochemometric modeling................. 103 Integration of genomic and proteomic data ............. 104 Proteomic databases: creation and analysis ............ 105 Introduction ... 105 Proteomic databases .......... 105 Human Proteomics Initiative 106 Protein Warehouse Database ................. 106 GenProtEC...... 106 Human Protein Index.......... 107 Protein Data Bank .............. 107 Universal Protein Resource .. 107 Protein interaction databases................. 108 Biomolecular Interaction Network Database................ 109 Proteome maps 109 The Protein Atlas................ 109 ENCODE......... 110 Metabolomics databases ..... 110 Functional Genomics Consortium............ 110 Application of bioinformatics in functional proteomics .............. 110 Us of bioinformatics in protein sequencing .............. 111 Bottom-up protein sequencing ............... 111 Top-down protein sequencing ................ 112 Protein structural database approach to drug design................. 112 Bioinformatics for high-throughput proteomics ....... 113 Companies with bioinformatic tools for proteomics . 114 - 6 - 5. Research in Proteomics ............... 117 Introduction.... 117 Basic biological research..... 117 Identification of novel human genes by comparative proteomics ..... 118 Study of relationship between genes and proteins ....... 118 Protein knockout ................ 118 Antisense approach and proteomics... 118 RNAi and protein knockout ............... 118 Total knockout of cellular proteins ..... 119 Ribozymes and proteomics .. 119 Single-molecule photon stamping spectroscopy .......... 119 Functional genomics by mass spectrometry................ 120 Stable-isotope-dilution tandem mass spectrometry ..... 120 Single nucleotide polymorphism determination by TOF-MS ............. 120 Application of proteomic technologies in systems biology ............... 121 Signaling pathways and proteomics ... 121 Kinomics ... 121 Combinatorial RNAi for quantitative protein network analysis..... 122 Proteomics in neuroscience research ...... 122 Stem cell proteomics .......... 123 Proteomic studies of mesenchymal stem cells ........ 123 Proteomic profiling of neural stem cells ................. 123 Proteome Biology of Stem Cells Initiative .............. 124 Proteomic analysis of the cell cycle......... 124 Nitric oxide and proteomics . 124 A proteomic method for identification of cysteine S-nitrosylation sites ........... 125 Study of the nitroproteome .............. 125 Study of the phosphoproteome .............. 125 Study of the mitochondrial proteome...... 125 Proteomic technologies for study of mitochondrial proteomics.... 126 Cryptome....... 126 Study of protein transport in health and disease ......... 127 Proteomics research in the academic sector................ 127 Vanderbilt University's Center for Proteomics and Drug Actions.. 129 ProteomeBinders initiative................ 129 6. Pharmaceutical Applications of Proteomics ... 131 Current drug discovery process and its limitations ....... 131 Genomics-based drug discovery............. 132 Metabolomics technologies for drug discovery............. 132 Role of metabonomics in drug discovery . 133 Proteins and drug action ..... 133 Transcription-aided drug design ............. 134 Role of proteomic technologies in drug discovery ........ 134 Protein-expression mapping by 2DGE 135 Liquid chromatography-based drug discovery ........ 135 Role of MALDI mass spectrometry in drug discovery ................. 135 Oxford Genome Anatomy Project ...... 137 Proteins as drug targets...... 138 Ligands to capture the purine binding proteome.......... 138 Chemical probes to interrogate key protein families for drug discovery ............... 138 CellCarta® proteomics platform............. 139 ZeptoMARK Ô protein profiling system..... 139Identification of protein kinases as drug targets .......... 140 G-protein coupled receptors as drug targets ............... 140 Methods of study of GPCRs............... 141 Companies involved in GPCR-based drug discovery 141 GPCR localization database............... 142 Targeting mTOR signaling pathway......... 142 Serine hydrolases as drug targets .......... 143 Matrix metalloproteases as drug targets.. 144 Integrated bioinformatic analysis of proteomics data for drug discovery.............. 144 Drug design based on structural proteomics ............... 144 Protein crystallography for determining 3D structure of proteins 145 Automated 3D protein modeling........ 145 Companies involved in structure-based drug-design ................. 145 Integration of genomics and proteomics for drug discovery ............ 146 Ligand-receptor binding ...... 147 Aptamer protein binding ..... 147 Systematic Evolution of Ligands by Exponential Enrichment....... 147 Aptamers and high-throughput screening .............. 148 - 7 - Nucleic Acid Biotools...... 149 Aptamer beacons .......... 149 Peptide aptamers .......... 149 Riboreporters.. 150 Target identification and validation......... 150 Application of mass spectrometry for target identification.......... 151 Gene knockout and gene suppression for validating protein targets ............... 151 Laser-mediated protein knockout for target validation .............. 151 Integrated proteomics for drug discovery .............. 152 High-throughput proteomics 152 Companies involved in high-throughput proteomics 153 Drug discovery through protein-protein interaction studies............. 153 Protein-protein interaction as basis for drug target identification 154 Protein-PCNA interaction as basis for drug design... 154 Two-hybrid protein interaction technology for target identification................. 155 Biosensors for detection of small molecule-protein interactions .. 155 Protein-protein interaction maps ............ 156 ProNet (Myriad Genetics) ................. 156 Hybrigenics' maps of protein-protein interactions ... 156 CellZome's functional map of protein-protein interactions.......... 157 Mapping of protein-protein interactions by mass spectrometry... 157 Protein interaction map of Drosophila melanogaster ................. 158 Protein-interaction map of Wellcome Trust Sanger Institute....... 158 Inhibition of protein-protein interactions by peptide aptamers ........ 158 Selective disruption of proteins by small molecules...... 159 Post-genomic combinatorial biology approach............. 159 Differential p |
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