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市場調査レポート - 70918

プロテオミクス:技術・市場・企業

Proteomics - Technologies, Markets and Companies

発行 Jain Pharmabiotech
出版日 ページ情報 英文
価格
プロテオミクス:技術・市場・企業 Proteomics - Technologies, Markets and Companies
出版日: 2014年03月01日 ページ情報: 英文
概要

当レポートでは、ポストゲノム時代の創薬、分子診断、医療活動において重要な役割を担うプロテオミクス技術についての最新調査情報をまとめ、概略下記の構成でお届けします。

パートI

エグゼクティブサマリー

第1章 プロテオミクスについての基礎知識

  • イントロダクション
  • 歴史
  • 核酸、遺伝子、タンパク質
  • プロテオミクス(タンパク質構造機能学)
  • プロテオミクスとゲノミクス(ゲノム研究)
  • フェノミクス(フェノーム研究)
  • プロテオミクスとシステム生物学
  • 機能性人工タンパク質タンパク質

第2章 プロテオミクス技術

  • プロテオミクスを推進する重要技術
  • 試料調整
  • タンパク質分離技術
  • タンパク質検出
  • タンパク質の識別と解析
  • タンパク質シークエンシング
  • タンパク質定量のためのリアルタイムPCR(ポリメラーゼ連鎖反応)
  • 定量的プロテオミクス
  • 機能性プロテオミクス:タンパク質機能研究技術
  • RNA・タンパク質融合
  • 設計反復タンパク質(DRP:Designed Repeat Protein)
  • ナノバイオテクノロジーのプロテオミクス応用
  • タンパク質発現プロファイリング
  • 細胞ベースのタンパク質分析
  • タンパク質機能研究
  • タンパク質の構造究明
  • タンパク質機能の予測
  • 同位体標識ペプチドラベリング
  • 差別的プロテオミクス解析
  • 細胞マッププロテオミクス
  • 位相プロテオミクス
  • 細胞小器官または細胞内のプロテオミクス
  • 核小体プロテオミクス
  • グリコプロテオミクス技術
  • タンパク質解析への統合アプローチ
  • イメージング質量分析
  • プロテオミクスにおける自動化とロボット工学
  • レーザーキャプチャーマイクロダイセクション
  • プロテオミクス技術の用途についての結び

第3章 タンパク質バイオチップ技術

  • イントロダクション
  • タンパク質バイオチップの種類
  • プロテオミクス用組織マイクロアレイ技術
  • 分子診断に使用されるタンパク質バイオチップ
  • 生細胞マイクロアレイ
  • タンパク質アレイワークステーション
  • プロテオームアレイ
  • ペプチドアレイ
  • 表面プラズモン共鳴技術
  • ナノテクノロジー利用のタンパク質チップおよびマイクロアレイ
  • タンパク質バイオチップおよびマイクロアレイ技術に関与する企業

第4章 プロテオミクス関連の生物情報学

  • イントロダクション
  • プロテオミクスに使用される生物情報学ツール
  • プロテオミクスの医薬品応用に向けた生物情報学
  • ゲノミクスおよびプロテオミクス情報の統合
  • プロテオミクスデータベース:作成と分析
  • タンパク質識別に利用されるプロテオミクス
  • 機能性プロテオミクスにおける生物情報学の用途
  • タンパク質シークエンシングにおける生物情報学利用
  • 薬剤設計へのタンパク質構造データベース手法
  • 高スループットプロテオミクスのための生物情報学
  • プロテオミクスのための生物情報学ツールを提供する企業

第5章 プロテオミクス研究

  • イントロダクション
  • 生物学研究におけるプロテオミクスの用途
  • 構造ゲノミクスまたは構造プロテオミクス
  • タンパク質ノックアウト
  • リボザイムとプロテオミクス
  • 単分子プロテオミクス
  • システム生物学におけるプロテオミクス技術の用途
  • 神経科学研究におけるプロテオミクス
  • 幹細胞プロテオミクス
  • 細胞周期のプロテオミクス分析
  • 酸化窒素とプロテオミクス
  • フォスフォプロテオームの研究
  • ミトコンドリアプロテオームの研究
  • スギ
  • 健康・疾患におけるタンパク質輸送の研究
  • 学術界におけるプロテオミクス研究

第6章 プロテオミクスの医薬品利用

  • イントロダクション
  • 現行の創薬方法とその限界
  • 創薬におけるオミクスの役割
  • 標的疾患決定方法におけるプロテオミクスの役割
  • 創薬用プロテオミクスデータの生物情報学分析
  • 構造プロテオミクスに基く薬剤設計
  • 創薬のためのゲノミクス・プロテオミクス統合
  • リガンド受容体バインディング
  • 創薬のためのリボレポーター
  • 標的の識別と検証
  • 創薬への統合プロテオミクス
  • 高スループットプロテオミクス
  • タンパク質間相互作用研究からの創薬
  • ポストゲノミック連結生物学アプローチ
  • 微分プロテオミクス
  • ショットガンプロテオミクス
  • 創薬へのケモゲノミクスおよびケモプロテオミクス
  • 発現プロテオミクス:タンパク質レベルの定量
  • 標的発見におけるファージ抗体ライブラリーの役割
  • 創薬に向けたグリコプロテオミクスの用途
  • 創薬に向けたタンパク質マイクロアレイおよびバイオチップの役割
  • 創薬におけるプロテオミクスの役割についての結び
  • 薬剤開発に向けた指標としての「RNA」および「タンパク質」プロファイリングの比較
  • 毒性プロテオミクス
  • タンパク質・ペプチド治療
  • 遺伝子免疫法とプロテオミクス
  • プロテオミクスおよび遺伝子治療
  • 臨床薬剤開発におけるプロテオミクスの役割

第7章 ヒト医療におけるプロテオミクスの用途

  • イントロダクション
  • 臨床プロテオミクス
  • ヒト疾患の病態生理学
  • バイオマーカー識別へのプロテオミクスアプローチ
  • 分子診断におけるプロテオミクスの用途
  • 感染症におけるプロテオミクスの用途
  • 嚢胞性線維症におけるプロテオミクスの用途
  • 心疾患のプロテオミクス
  • 肺疾患研究におけるプロテオミクス技術
  • 腎疾患におけるプロテオミクスの用途
  • 眼球疾患のプロテオミクス
  • 内耳疾患におけるプロテオミクス利用
  • 老化研究におけるプロテオミクス利用
  • プロテオミクスと栄養学

第8章 腫瘍プロテオミクス

  • イントロダクション
  • がん研究のためのプロテオミクス技術
  • さまざまな臓器系のがんにおけるプロテオミクス利用
  • がんバイオマーカーの診断利用
  • NCI(国立癌研究所)の臨床プロテオミクス技術センターネットワーク
  • プロテオミクスと腫瘍免疫学
  • プロテオミクスと腫瘍侵襲性研究
  • 抗がん剤の創薬と開発
  • 腫瘍プロテオミクスの将来展望
  • 腫瘍学へのプロテオミクス応用に関与する企業

第9章 神経プロテオミクス

  • イントロダクション
  • プリオン病のプロテオミクス
  • タンパク質の誤った折り畳みと神経変性疾患
  • プロテオミクスと脱髄疾患
  • 神経遺伝疾患のプロテオミクス
  • 中枢神経系外傷のプロテオミクス
  • 中枢神経系老化のプロテオミクス
  • 精神疾患の神経プロテオミクス
  • プロテオミクスに基く神経診断
  • 血液脳関門のプロテオミクス
  • 神経学における神経プロテオミクスの将来展望

第10章 プロテオミクスの商業局面

  • イントロダクション
  • プロテオミクス技術にとっての有望市場
  • 事業および戦略の考察
  • プロテオミクスにおける市場推進要因
  • プロテオミクスが向き合う課題

第11章 プロテオミクスの将来

  • ゲノミクスからプロテオミクスへ
  • 新たなプロテオミクス技術への需要
  • 台頭しつつあるプロテオミクス技術
  • 母集団プロテオミクス
  • 比較プロテオーム研究
  • ヒトプロテオーム組織
  • ヒト唾液プロテオーム
  • プロテオミクスにおける産学共同
  • 今後の医療におけるプロテオミクスの役割

第12章 参考資料

図表

パートII

第13章 プロテオミクス開発に関与する企業

  • イントロダクション
  • 代表的企業のプロフィール
  • 協力関係

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目次

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 478 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 2011 and are projected to years 2016 and 2021. The largest expansion will be in bioinformatics and protein biochip technologies. Important areas of application are cancer and neurological disorders

Table of Contents

Part I

0. Executive Summary 18

1. Basics of Proteomics 20

  • Introduction 20
  • History 20
  • Nucleic acids, genes and proteins 21
  • Genome 21
  • DNA 22
  • RNA 22
  • MicroRNAs 22
  • Decoding of mRNA by the ribosome 23
  • Genes 24
  • Alternative splicing 24
  • Transcription 25
  • Gene regulation 25
  • Gene expression 26
  • Chromatin 26
  • Golgi complex 27
  • Proteins 27
  • Spliceosome 28
  • Functions of proteins 28
  • Inter-relationship of protein, mRNA and DNA 29
  • Proteomics 30
  • Mitochondrial proteome 31
  • S-nitrosoproteins in mitochondria 31
  • Proteomics and genomics 32
  • Classification of proteomics 34
  • Levels of functional genomics and various "omics" 34
  • Glycoproteomics 35
  • Transcriptomics 35
  • Metabolomics 35
  • Cytomics 36
  • Phenomics 36
  • Impact of the genetic factors on the human proteome 36
  • Proteomics and systems biology 37
  • Functional synthetic proteins 37

2. Proteomic Technologies 40

  • Key technologies driving proteomics 40
  • Sample preparation 41
  • New trends in sample preparation 41
  • Pressure Cycling Technology 42
  • Protein separation technologies 42
  • High resolution 2DGE 42
  • Variations of 2D gel technology 43
  • Limitations of 2DGE and measures to overcome these 43
  • 1-D sodium dodecyl sulfate (SDS) PAGE 43
  • Capillary electrophoresis systems 44
  • Head column stacking capillary zone electrophoresis 44
  • Removal of albumin and IgG 44
  • SeraFILE™ separations platform 45
  • Companies with protein separation technologies 45
  • Protein purification 47
  • Technologies for protein purification 47
  • Applications of protein purification 47
  • Protein detection 47
  • Protein identification and characterization 48
  • Mass spectrometry (MS) 48
  • Companies involved in mass spectrometry 48
  • Electrospray ionization 49
  • Desorption electrospray ionization MS 50
  • Mirosaic 3500 MiD 51
  • Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 51
  • Cryogenic MALDI- Fourier Transform Mass Spectrometry 53
  • Stable-isotope-dilution tandem mass spectrometry 53
  • HUPO Gold MS Protein Standard 53
  • High performance liquid chromatography 54
  • Multidimensional protein identification technology (MudPIT) 54
  • Multiple reaction monitoring assays 54
  • Peptide mass fingerprinting 55
  • Combination of protein separation technologies with mass spectrometry 55
  • Combining capillary electrophoresis with mass spectrometry 55
  • 2D PAGE and mass spectrometry 56
  • Quantification of low abundance proteins 56
  • SDS-PAGE 56
  • Antibodies and proteomics 57
  • Detection of fusion proteins 57
  • Labeling and detection of proteins 57
  • Fluorescent labeling of proteins in living cells 58
  • Combination of microspheres with fluorescence 58
  • Self-labeling protein tags 58
  • Analysis of peptides 59
  • C-terminal peptide analysis 60
  • Differential Peptide Display 60
  • Peptide analyses using NanoLC-MS 60
  • Protein sequencing 61
  • Real-time PCR for protein quantification 62
  • Quantitative proteomics 62
  • MS-based quantitative proteomics 62
  • MS and cryo-electron tomography 62
  • Selected reaction monitoring MS 63
  • Functional proteomics: technologies for studying protein function 63
  • Functional genomics by mass spectrometry 63
  • LC-MS-based method for annotating the protein-coding genome 64
  • RNA-Protein fusions 64
  • Designed repeat proteins 64
  • Application of nanobiotechnology to proteomics 65
  • Nanoproteomics 65
  • Nanoflow liquid chromatography 65
  • Nanopores for phosphoprotein analysis 66
  • Nanotube electronic biosensor for proteomics 66
  • Protein nanocrystallography 66
  • Single-molecule mass spectrometry using a nanopore 67
  • Nanoelectrospray ionization 67
  • Nanoproteomics for discovery of protein biomarkers in the blood 67
  • QD-protein nanoassembly 68
  • Nanoparticle barcodes 68
  • Biobarcode assay for proteins 68
  • Nanopore-based protein sequencing 69
  • Nanoscale protein analysis 70
  • Nanoscale mechanism for protein engineering 70
  • Nanotube electronic biosensor 71
  • Nanotube-vesicle networks for study of membrane proteins 71
  • Nanowire transistor for the detection of protein-protein interactions 71
  • Qdot-nanocrystals 72
  • Resonance Light Scattering technology 72
  • Study of single membrane proteins at subnanometer resolution 72
  • Protein expression profiling 73
  • Cell-based protein assays 73
  • Living cell-based assays for protein function 74
  • Companies developing cell-based protein assays 74
  • Protein function studies 75
  • Transcriptionally Active PCR 75
  • Protein-protein interactions 75
  • Yeast two-hybrid system 77
  • Membrane one-hybrid method 78
  • Protein affinity chromatography 78
  • Phage display 79
  • Fluorescence Resonance Energy Transfer 79
  • Bioluminescence Resonance Energy Transfer 79
  • Detection Enhanced Ubiquitin Split Protein Sensor technology 80
  • Protein-fragment complementation system 80
  • In vivo study of protein-protein interactions 80
  • Bacterial protein interaction studies for assigning function 81
  • Computational prediction of interactions 81
  • Interactome 81
  • Protein-protein interactions and drug discovery 82
  • Companies with technologies for protein-protein interaction studies 83
  • Protein-DNA interaction 83
  • Determination of protein structure 84
  • X-Ray crystallography 84
  • Nuclear magnetic resonance 85
  • Electron spin resonance 86
  • Prediction of protein structure 86
  • Protein tomography 86
  • X-ray scattering-based method for determining the structure of proteins 87
  • Prediction of protein function 87
  • Three-dimensional proteomics for determination of function 88
  • An algorithm for genome-wide prediction of protein function 88
  • Monitoring protein function by expression profiling 89
  • Isotope-coded affinity tag peptide labeling 89
  • Differential Proteomic Panning 90
  • Cell map proteomics 90
  • Topological proteomics 90
  • Organelle or subcellular proteomics 91
  • Nucleolar proteomics 92
  • Glycoproteomic technologies 92
  • High-sensitivity glycoprotein analysis 92
  • Fluorescent in vivo imaging of glycoproteins 92
  • Integrated approaches for protein characterization 93
  • Imaging mass spectrometry 93
  • IMS technologies 93
  • Applications of IMS 94
  • The protein microscope 94
  • Tag-Mass IMS 95
  • Automation and robotics in proteomics 95
  • Western blot 95
  • Limitations of WB 96
  • Innovations in WB 96
  • Capillary electrophoresis and WB 96
  • Chemiluminescent western blotting 96
  • Fluorescent WB 97
  • Microfluidics and WB 97
  • Multiplexing WB 98
  • Applications of Western blot 98
  • Research applications of Western blot 98
  • Molecular diagnostic applications of Western blot 99
  • Companies involved in Western blotting technologies 99
  • Laser capture microdissection 100
  • Microdissection techniques used for proteomics 100
  • Uses of LCM in combination with proteomic technologies 101
  • Concluding remarks about applications of proteomic technologies 101
  • Precision proteomics 102

3. Protein biochip technology 104

  • Introduction 104
  • Types of protein biochips 105
  • ProteinChip 105
  • Applications and advantages of ProteinChip 106
  • ProteinChip Biomarker System 106
  • Matrix-free ProteinChip Array 107
  • Aptamer-based protein biochip 107
  • Fluorescence planar wave guide technology-based protein biochips 108
  • Lab-on-a-chip for protein analysis 108
  • Biochips for peptide arrays 109
  • Microfluidic biochips for proteomics 109
  • Protein biochips for high-throughput expression 110
  • Nucleic Acid-Programmable Protein Array 110
  • High-density protein microarrays 110
  • HPLC-Chip for protein identification 111
  • Antibody microarrays 111
  • Integration of protein array and image analysis 111
  • Tissue microarray technology for proteomics 112
  • Protein biochips in molecular diagnostics 112
  • A force-based protein biochip 113
  • L1 chip and lipid immobilization 113
  • Multiplexed Protein Profiling on Microarrays 113
  • Live cell microarrays 114
  • ProteinArray Workstation 114
  • Proteome arrays 115
  • The Yeast ProtoArray 115
  • ProtoArray™ Human Protein Microarray 115
  • TRINECTIN proteome chip 116
  • Peptide arrays 116
  • Surface plasmon resonance technology 117
  • Biacore's SPR 117
  • FLEX CHIP 117
  • Combination of surface plasmon resonance and MALDI-TOF 118
  • Protein chips/microarrays using nanotechnology 118
  • Nanoparticle protein chip 118
  • Protein nanobiochip 119
  • Protein nanoarrays 119
  • Self-assembling protein nanoarrays 119
  • Companies involved in protein biochip/microarray technology 120

4. Bioinformatics in Relation to Proteomics 124

  • Introduction 124
  • Bioinformatic tools for proteomics 124
  • Testing of SELDI-TOF MS Proteomic Data 124
  • BioImagine's ProteinMine 125
  • Bioinformatics for pharmaceutical applications of proteomics 125
  • In silico search of drug targets by Biopendium 125
  • Compugen's LEADS 126
  • DrugScore 126
  • Proteochemometric modeling 126
  • Integration of genomic and proteomic data 127
  • Proteomic databases: creation and analysis 128
  • Introduction 128
  • Proteomic databases 128
  • GenProtEC 129
  • Human Protein Atlas 129
  • Human Proteomics Initiative 130
  • International Protein Index 131
  • Proteome maps 131
  • Protein Structure Initiative - Structural Genomics Knowledgebase 131
  • Protein Warehouse Database 131
  • Protein Data Bank 132
  • Repository for raw data from proteomics MS 132
  • Universal Protein Resource 132
  • Protein interaction databases 133
  • Biomolecular Interaction Network Database 134
  • ENCODE 134
  • Functional Genomics Consortium 134
  • Human Proteinpedia 135
  • ProteinCenter 135
  • Databases of the National Center for Biotechnology Information 135
  • Bioinformatics for protein identification 136
  • Application of bioinformatics in functional proteomics 136
  • Use of bioinformatics in protein sequencing 136
  • Bottom-up protein sequencing 137
  • Top-down protein sequencing 138
  • Protein structural database approach to drug design 138
  • Bioinformatics for high-throughput proteomics 138
  • Bioinformatics for protein-protein interactions 139
  • Companies with bioinformatic tools for proteomics 140

5. Research in Proteomics 142

  • Introduction 142
  • Applications of proteomics in biological research 142
  • Identification of novel human genes by comparative proteomics 142
  • Study of relationship between genes and proteins 143
  • Characterization of histone codes 143
  • Structural genomics or structural proteomics 144
  • Protein Structure Factory 145
  • Protein Structure Initiative 145
  • Studies on protein structure at Argonne National Laboratory 146
  • Structural Genomics Consortium 146
  • Protein knockout 147
  • Antisense approach and proteomics 147
  • RNAi and protein knockout 147
  • Total knockout of cellular proteins 148
  • Ribozymes and proteomics 148
  • Single molecule proteomics 148
  • Single-molecule photon stamping spectroscopy 148
  • Single nucleotide polymorphism determination by TOF-MS 149
  • Application of proteomic technologies in systems biology 149
  • Signaling pathways and proteomics 150
  • Kinomics 150
  • Combinatorial RNAi for quantitative protein network analysis 150
  • Proteomics in neuroscience research 151
  • Stem cell proteomics 151
  • Comparative proteomic analysis of somatic cells, iPSCs and ESCs 152
  • hESC phosphoproteome 152
  • Proteomic studies of mesenchymal stem cells 152
  • Proteomics of neural stem cells 153
  • Proteome Biology of Stem Cells Initiative 153
  • Proteomic analysis of the cell cycle 154
  • Nitric oxide and proteomics 154
  • A proteomic method for identification of cysteine S-nitrosylation sites 154
  • Study of the nitroproteome 155
  • Study of the phosphoproteome 155
  • Study of the mitochondrial proteome 156
  • Proteomic technologies for study of mitochondrial proteomics 156
  • Cryptome 157
  • Study of protein transport in health and disease 157
  • Ancient proteomics 157
  • Proteomics research in the academic sector 158
  • Netherlands Proteins@Work 160
  • ProteomeBinders initiative 160
  • Rutgers University's Center for Integrative Proteomics Research 160
  • Vanderbilt University's Center for Proteomics and Drug Actions 161

6. Pharmaceutical Applications of Proteomics 162

  • Introduction 162
  • Current drug discovery process and its limitations 162
  • Role of omics in drug discovery 163
  • Genomics-based drug discovery 163
  • Metabolomics technologies for drug discovery 164
  • Role of metabonomics in drug discovery 164
  • Basis of proteomics approach to drug discovery 165
  • Proteins and drug action 165
  • Transcription-aided drug design 166
  • Role of proteomic technologies in drug discovery 166
  • Liquid chromatography-based drug discovery 167
  • Capture compound mass spectrometry 168
  • Protein-expression mapping by 2DGE 168
  • Role of MALDI mass spectrometry in drug discovery 168
  • Structural proteomics and drug discovery 168
  • Tissue imaging mass spectrometry 169
  • Companies using MALDI for drug discovery 170
  • Oxford Genome Anatomy Project 171
  • Proteins as drug targets 171
  • Ligands to capture the purine binding proteome 172
  • Chemical probes to interrogate key protein families for drug discovery 172
  • Global proteomics for pharmacodynamics 172
  • CellCarta® proteomics platform 173
  • ZeptoMARK™ protein profiling system 173
  • Role of proteomics in targeting disease pathways 174
  • Dynamic proteomics 174
  • Identification of protein kinases as drug targets 174
  • Mechanisms of action of kinase inhibitors 175
  • G-protein coupled receptors as drug targets 175
  • Methods of study of GPCRs 176
  • Cell-based assays for GPCR 176
  • Companies involved in GPCR-based drug discovery 177
  • GPCR localization database 178
  • Matrix metalloproteases as drug targets 178
  • PDZ proteins as drug targets 179
  • Proteasome as drug target 179
  • Serine hydrolases as drug targets 180
  • Targeting mTOR signaling pathway 180
  • Targeting caspase-8 for anticancer therapeutics 181
  • Bioinformatic analysis of proteomics data for drug discovery 182
  • Drug design based on structural proteomics 182
  • Protein crystallography for determining 3D structure of proteins 182
  • Automated 3D protein modeling 183
  • Drug targeting of flexible dynamic proteins 183
  • Companies involved in structure-based drug-design 183
  • Integration of genomics and proteomics for drug discovery 184
  • Ligand-receptor binding 185
  • Role of proteomics in study of ligand-receptor binding 185
  • Measuring drug binding of proteins 186
  • Aptamer protein binding 186
  • Systematic Evolution of Ligands by Exponential Enrichment 186
  • Aptamers and high-throughput screening 187
  • Nucleic Acid Biotools 187
  • Aptamer beacons 188
  • Peptide aptamers 188
  • Riboreporters for drug discovery 188
  • Target identification and validation 189
  • Application of mass spectrometry for target identification 189
  • Gene knockout and gene suppression for validating protein targets 189
  • Laser-mediated protein knockout for target validation 190
  • Integrated proteomics for drug discovery 190
  • High-throughput proteomics 191
  • Companies involved in high-throughput proteomics 191
  • Drug discovery through protein-protein interaction studies 192
  • Protein-protein interaction as basis for drug target identification 192
  • Protein-PCNA interaction as basis for drug design 193
  • Two-hybrid protein interaction technology for target identification 193
  • Biosensors for detection of small molecule-protein interactions 194
  • Protein-protein interaction maps 194
  • ProNet (Myriad Genetics) 194
  • Hybrigenics' maps of protein-protein interactions 195
  • CellZome's functional map of protein-protein interactions 195
  • Mapping of protein-protein interactions by mass spectrometry 196
  • Protein interaction map of Drosophila melanogaster 196
  • Protein-interaction map of Wellcome Trust Sanger Institute 196
  • Protein-protein interactions as targets for therapeutic intervention 197
  • Inhibition of protein-protein interactions by peptide aptamers 197
  • Selective disruption of proteins by small molecules 197
  • Post-genomic combinatorial biology approach 198
  • Differential proteomics 198
  • Shotgun proteomics 199
  • Chemogenomics/chemoproteomics for drug discovery 199
  • Chemoproteomics-based drug discovery 200
  • Companies involved in chemogenomics/chemoproteomics 201
  • Activity-based proteomics 202
  • Locus Discovery technology 202
  • Automated ligand identification system 203
  • Expression proteomics: protein level quantification 204
  • Role of phage antibody libraries in target discovery 204
  • Analysis of posttranslational modification of proteins by MS 204
  • Phosphoproteomics for drug discovery 205
  • Application of glycoproteomics for drug discovery 205
  • Role of carbohydrates in proteomics 205
  • Challenges of glycoproteomics 206
  • Companies involved in glycoproteomics 206
  • Role of protein microarrays/ biochips for drug discovery 207
  • Protein microarrays vs DNA microarrays for high-throughput screening 207
  • BIA-MS biochip for protein-protein interactions 208
  • ProteinChip with Surface Enhanced Neat Desorption 208
  • Protein-domains microarrays 208
  • Some limitations of protein biochips 209
  • Concluding remarks about role of proteomics in drug discovery 209
  • RNA versus protein profiling as guide to drug development 210
  • RNA as drug target 210
  • Combination of RNA and protein profiling 211
  • RNA binding proteins 211
  • Toxicoproteomics 211
  • Hepatotoxicity 211
  • Nephrotoxicity 212
  • Cardiotoxicity 213
  • Neurotoxicity 213
  • Protein/peptide therapeutics 213
  • Alphabody technology for improving protein therapeutics 213
  • Peptide-based drugs 214
  • Phylomer® peptides 214
  • Cryptein-based therapeutics 214
  • Synthetic proteins and peptides as pharmaceuticals 215
  • Genetic immunization and proteomics 216
  • Proteomics and gene therapy 216
  • Role of proteomics in clinical drug development 217
  • Pharmacoproteomics 217
  • Role of proteomics in clinical drug safety 217

7. Application of Proteomics in Human Healthcare 220

  • Introduction 220
  • Clinical proteomics 221
  • Definition and standards 221
  • Vermillion's Clinical Proteomics Program 221
  • Pathophysiology of human diseases 222
  • Diseases due to misfolding of proteins 222
  • Mechanism of protein folding 223
  • Nanoproteomics for study of misfolded proteins 224
  • Therapies for protein misfolding 224
  • Intermediate filament proteins 225
  • Significance of mitochondrial proteome in human disease 226
  • Proteome of Saccharomyces cerevisiae mitochondria 226
  • Rat mitochondrial proteome 226
  • Proteomic approaches to biomarker identification 227
  • The ideal biomarker 227
  • Proteomic technologies for biomarker discovery 227
  • MALDI mass spectrometry for biomarker discovery 228
  • BAMF™ Technology 228
  • Protein biochips/microarrays and biomarkers 229
  • Affinity proteomics for discovery of biomarkers 229
  • Antibody array-based biomarker discovery 229
  • Discovery of biomarkers by MAb microarray profiling 230
  • Tumor-specific serum peptidome patterns 230
  • Search for protein biomarkers in body fluids 231
  • Challenges and strategies for discovey of protein biomarkers in plasma 231
  • 3-D structure of CD38 as a biomarker 232
  • BD™ Free Flow Electrophoresis System 232
  • Isotope tags for relative and absolute quantification 232
  • N-terminal peptide isolation from human plasma 233
  • Plasma protein microparticles as biomarkers 233
  • Proteome partitioning 234
  • SISCAPA method for quantitating proteins and peptides in plasma 234
  • Stable isotope tagging methods 234
  • Technology to measure both the identity and size of the biomarker 235
  • Biomarkers in the urinary proteome 235
  • Application of proteomics in molecular diagnosis 236
  • Proximity ligation assay 237
  • Protein patterns 237
  • Proteomic tests on body fluids 237
  • Cyclical amplification of proteins 239
  • Applications of proteomics in infections 239
  • MALDI-TOF MS for microbial identification 239
  • Role of proteomics in virology 240
  • Study of interaction of proteins with viruses 240
  • Role of proteomics in bacteriology 241
  • Epidemiology of bacterial infections 241
  • Proteomic approach to bacterial pathogenesis 241
  • Vaccines for bacterial infections 242
  • Protein profiles associated with bacterial drug resistance 242
  • Analyses of the parasite proteome 242
  • Application of proteomics in cystic fibrosis 243
  • Proteomics of cardiovascular diseases 243
  • Pathomechanism of cardiovascular diseases 243
  • Protein misfolding in cardiac dysfunction 244
  • Study of cardiac mitochondrial proteome in myocardial ischemia 244
  • Cardiac protein databases 245
  • Proteomics of dilated cardiomyopathy and heart failure 245
  • Proteomic biomarkers of cardiovascular diseases 245
  • Role of proteomics in cardioprotection 246
  • Role of proteomics in heart transplantation 246
  • Future of application of proteomics in cardiology 246
  • Proteomic technologies for research in pulmonary disorders 247
  • Application of proteomics in renal disorders 248
  • Diagnosis of renal disorders 248
  • Proteomic biomarkers of acute kidney injury 248
  • Cystatin C as biomarker of glomerular filtration rate 249
  • Protein biomarkers of nephritis 249
  • Proteomics and kidney stones 249
  • Proteomics of eye disorders 249
  • Proteomics of cataract 250
  • Proteomics of diabetic retinopathy 251
  • Retinal dystrophies 251
  • Use of proteomics in inner ear disorders 251
  • Use of proteomics in aging research 251
  • Alteration of glycoproteins during aging 252
  • Removal of altered cellular proteins in aging 252
  • Study of the role of Parkin in modulating aging 253
  • Proteomics and nutrition 253

8. Oncoproteomics 254

  • Introduction 254
  • Proteomic technologies for study of cancer 255
  • Application of CellCarta technology for oncology 255
  • Accentuation of differentially expressed proteins using phage technology 255
  • Cancer tissue proteomics 255
  • Dynamic cell proteomics in response to a drug 256
  • Desorption electrospray ionization for cancer diagnosis 256
  • Id proteins as targets for cancer therapy 257
  • Identification of oncogenic tyrosine kinases using phosphoproteomics 257
  • Laser capture microdissection technology and cancer proteomics 257
  • Mass spectrometry for identification of oncogenic chimeric proteins 258
  • Proteomic analysis of cancer cell mitochondria 258
  • Proteomic study of p53 259
  • Human Tumor Gene Index 259
  • Integration of cancer genomics and proteomics 259
  • Role of proteomics in study of cancer stem cell biology 260
  • Single-cell protein expression analysis by microfluidic techniques 260
  • Use of proteomics in cancers of various organ systems 260
  • Proteomics of brain tumors 260
  • Malignant glial tumors 260
  • Meningiomas 261
  • DESI-MS for intraoperative diagnosis of brain tumors 261
  • Proteomics of breast cancer 262
  • Integration of proteomic and genomic data for breast cancer 263
  • Proteomics of colorectal cancer 264
  • Proteomics of esophageal cancer 264
  • Proteomics of hepatic cancer 265
  • Proteomics of leukemia 265
  • Proteomics of lung cancer 266
  • Proteomics of pancreatic cancer 267
  • Proteomics of prostate cancer 267
  • Proteomics of renal cancer 268
  • Diagnostic use of cancer biomarkers 268
  • Proteomic technologies for tumor biomarkers 269
  • Nuclear matrix proteins (NMPs) 269
  • Antiannexins as tumor markers in lung cancer 270
  • NCI's Network of Clinical Proteomic Technology Centers 270
  • Proteomics and tumor immunology 271
  • Proteomics and study of tumor invasiveness 272
  • Anticancer drug discovery and development 272
  • Kinase-targeted drug discovery in oncology 272
  • Anticancer drug targeting: functional proteomics screen of proteases 273
  • Small molecule inhibitors of cancer-related proteins 273
  • Role of proteomics in studying drug resistance in cancer 273
  • Future prospects of oncoproteomics 274
  • Clinical Proteomic Tumor Analysis Consortium 274
  • Companies involved in application of proteomics to oncology 275

9. Neuroproteomics 278

  • Introduction 278
  • Application of proteomics for the study of nervous system 278
  • Proteomics of prion diseases 279
  • Normal function of prions in the brain 279
  • Diseases due to pathological prion protein 279
  • Transmissible spongiform encephalopathies 280
  • Creutzfeld-Jakob disease 280
  • Bovine spongiform encephalopathy 280
  • Variant Creutzfeldt-Jakob disease 281
  • Protein misfolding and neurodegenerative disorders 281
  • Ion channel link for protein-misfolding disease 281
  • Detection of misfolded proteins 281
  • Neurodegenerative disorders with protein abnormalities 282
  • Alzheimer disease 284
  • Common denominators of Alzheimer and prion diseases 284
  • Parkinson disease 285
  • Amyotrophic lateral sclerosis 285
  • Proteomics and glutamate repeat disorders 286
  • Proteomics and Huntington's disease 286
  • Proteomics and demyelinating diseases 287
  • Proteomics of neurogenetic disorders 287
  • Fabry disease 287
  • GM1 gangliosidosis 288
  • Quantitative proteomics and familial hemiplegic migraine 288
  • Proteomics of spinal muscular atrophy 289
  • Proteomics of CNS trauma 289
  • Proteomics of traumatic brain injury 289
  • Chronic traumatic encephalopathy and ALS 290
  • Proteomics of cerebrovascular disease 290
  • Proteomics of CNS aging 291
  • Protein aggregation as a bimarker of aging 291
  • Neuroproteomics of psychiatric disorders 292
  • Neuroproteomic of cocaine addiction 292
  • Neurodiagnostics based on proteomics 293
  • Disease-specific proteins in the cerebrospinal fluid 293
  • Tau proteins 294
  • CNS tissue proteomics 294
  • Diagnosis of CNS disorders by examination of proteins in urine 296
  • Diagnosis of CNS disorders by examination of proteins in the blood 296
  • Serum pNF-H as biomarker of CNS damage 297
  • Proteomics of BBB 297
  • Future prospects of neuroproteomics in neurology 297
  • HUPO's Pilot Brain Proteome Project 299

10. Proteomics Markets 300

  • Introduction 300
  • Potential markets for proteomic technologies 300
  • Bioinformatics markets for proteomics 301
  • Markets for protein separation technologies 301
  • Markets for 2D gel electrophoresis 301
  • Market trends in protein separation technolgies 302
  • Protein purification markets 302
  • Mass spectrometry markets 302
  • Markets for MALDI for drug discovery 303
  • Markets for nuclear magnetic resonance spectroscopy 303
  • Market for structure-based drug design 303
  • Markets for protein biomarkers 304
  • Markets for cell-based protein assays 304
  • Protein biochip markets 304
  • Western blot markets 304
  • Geographical distribution of proteomics technologies markets 305
  • Business and strategic considerations 305
  • Cost of protein structure determination 305
  • Opinion surveys of the scientist consumers of proteomic technologies 305
  • Opinions on mass spectrometry 305
  • Opinions on bioinformatics and proteomic databases 306
  • Systems for in vivo study of protein-protein interactions 306
  • Perceptions of the value of protein biochip/microfluidic systems 306
  • Small versus big companies 306
  • Expansion in proteomics according to area of application 307
  • Growth trends in cell-based protein assay market 307
  • Challenges for development of cell-based protein assays 307
  • Future trends and prospects of cell-based protein assays 308
  • Strategic collaborations 308
  • Analysis of proteomics collaborations according to types of companies 308
  • Types of proteomic collaborations 309
  • Proteomics collaborations according to application areas 309
  • Analysis of proteomics collaborations: types of technologies 310
  • Collaborations based on protein biochip technology 310
  • Concluding remarks about proteomic collaborations 311
  • Proteomic patents 311
  • Market drivers in proteomics 312
  • Needs of the pharmaceutical industry 312
  • Need for outsourcing proteomic technologies 312
  • Funding of proteomic companies and research 312
  • Technical advances in proteomics 313
  • Changing trends in healthcare in future 313
  • Challenges facing proteomics 313
  • Magnitude and complexity of the task 313
  • Technical challenges 314
  • Limitations of proteomics 314
  • Limitations of 2DGE 314
  • Limitations of mass spectrometry techniques 314
  • Complexity of the pharmaceutical proteomics 315
  • Unmet needs in proteomics 315

11. Future of Proteomics 318

  • Genomics to proteomics 318
  • Faster technologies 318
  • FLEXGene repository 318
  • Need for new proteomic technologies 319
  • Emerging proteomic technologies 320
  • Detection of alternative protein isoforms 320
  • Direct protein identification in large genomes by mass spectrometry 320
  • Proteome identification kits with stacked membranes 320
  • Vacuum deposition interface 321
  • In vitro protein biosynthesis 321
  • Proteome mining with adenosine triphosphate 321
  • Proteome-scale purification of human proteins from bacteria 321
  • Proteostasis network 322
  • Cytoproteomics 322
  • Subcellular proteomics 322
  • Individual cell proteomics 323
  • Live cell proteomics 323
  • Fluorescent proteins for live-cell imaging 324
  • Membrane proteomics 324
  • Identification of membrane proteins by tandem MS of protein ions 324
  • Solid state NMR for study of nanocrystalline membrane proteins 325
  • Multiplex proteomics 325
  • High-throughput for proteomics 325
  • Future directions for protein biochip application 326
  • Bioinformatics for proteomics 326
  • High-Throughput Crystallography Consortium 326
  • Study of protein folding by IBM's Blue Gene 327
  • Study of proteins by atomic force microscopy 327
  • Population proteomics 327
  • Comparative proteome analysis 328
  • Human Proteome Organization 328
  • Cell-based Human Proteome Project 329
  • Human Salivary Proteome 329
  • Academic-commercial collaborations in proteomics 330
  • Indiana Centers for Applied Protein Sciences 330
  • Role of proteomics in the healthcare of the future 330
  • Proteomics and molecular medicine 330
  • Proteodiagnostics 331
  • Proteomics and personalized medicine 331
  • Targeting the ubiquitin pathway for personalized therapy of cancer 332
  • Protein patterns and personalized medicine 332
  • Personalizing interferon therapy of hepatitis C virus 334
  • Protein biochips and personalized medicine 334
  • Combination of diagnostics and therapeutics 335
  • Future prospects 335

12. References 336

Tables

  • Table 1-1: Landmarks in the evolution of proteomics 20
  • Table 1-2: Comparison of DNA and protein 29
  • Table 1-3: Comparison of mRNA and protein 29
  • Table 1-4: Methods of analysis at various levels of functional genomics 35
  • Table 2-1: Proteomics technologies 40
  • Table 2-2: Protein separation technologies of selected companies 45
  • Table 2-3: Companies supplying mass spectrometry instruments 48
  • Table 2-4: Companies involved in cell-based protein assays 74
  • Table 2-5: Methods used for the study of protein-protein interactions 76
  • Table 2-6: A selection of companies involved in protein-protein interaction studies 83
  • Table 2-7: Companies involved in Western blotting 99
  • Table 2-8: Proteomic technologies used with laser capture microdissection 101
  • Table 3-1: Applications of protein biochip technology 104
  • Table 3-2: Selected companies involved in protein biochip/microarray technology 120
  • Table 4-1: Proteomic databases and other Internet sources of proteomics information 128
  • Table 4-2: Protein interaction databases available on the Internet 133
  • Table 4-3: Bioinformatic tools for proteomics from academic sources 139
  • Table 4-4: Selected companies involved in bioinformatics for proteomics 140
  • Table 5-1: Applications of proteomics in basic biological research 142
  • Table 5-2: A sampling of proteomics research projects in academic institutions 158
  • Table 6-1: Pharmaceutical applications of proteomics 162
  • Table 6-2: Selected companies relevant to MALDI-MS for drug discovery 170
  • Table 6-3: Selected companies involved in GPCR-based drug discovery 177
  • Table 6-4: Companies involved in drug design based on structural proteomics 184
  • Table 6-5: Proteomic companies with high-throughput protein expression technologies 191
  • Table 6-6: Selected companies involved in chemogenomics/chemoproteomics 201
  • Table 6-7: Companies involved in glycoproteomic technologies 207
  • Table 7-1: Applications of proteomics in human healthcare 220
  • Table 7-2: Eye disorders and proteomic approaches 250
  • Table 8-1: Companies involved in applications of proteomics to oncology 275
  • Table 9-1: Neurodegenerative diseases with underlying protein abnormality 282
  • Table 9-2: Disease-specific proteins in the cerebrospinal fluid of patients 293
  • Table 10-1: Potential markets for proteomic technologies 2013-2023 300
  • Table 10-2: 2013 revenues of major companies from protein separation technologies 301
  • Table 10-3: Geographical distribution of markets for proteomic technologies 2013-2023 305
  • Table 11-1: Role of proteomics in personalizing strategies for cancer therapy 332

Figures

  • Figure 1-1: A schematic miRNA pathway 23
  • Figure 1-2: Relationship of DNA, RNA and protein in the cell 30
  • Figure 1-3: Protein production pathway from gene expression to functional protein with controls 32
  • Figure 1-4: Parallels between functional genomics and proteomics 33
  • Figure 2-1: Proteomics: flow from sample preparation to characterization 41
  • Figure 2-2: The central role of spectrometry in proteomics 48
  • Figure 2-3: Electrospray ionization (ESI) 49
  • Figure 2-4: Matrix-Assisted Laser Desorption/Ionization (MALDI) 52
  • Figure 2-5: Scheme of bio-bar-code assay 69
  • Figure 2-6: A diagrammatic presentation of yeast two-hybrid system 77
  • Figure 3-1: ProteinChip System 106
  • Figure 3-2: Surface plasma resonance (SPR) 117
  • Figure 4-1: Role of bioinformatics in integrating genomic/proteomic-based drug discovery 127
  • Figure 4-2: Bottom-up and top-down approaches for protein sequencing 137
  • Figure 6-1: Drug discovery process 163
  • Figure 6-2: Regulatory changes induced by drugs and implemented at the proteins level 166
  • Figure 6-3: Relation of proteome to genome, diseases and drugs 167
  • Figure 6-4: The mTOR pathways 181
  • Figure 6-5: Steps in shotgun proteomics 199
  • Figure 6-6: Chemogenomic approach to drug discovery (3-Dimensional Pharmaceuticals) 200
  • Figure 8-1: Relation of oncoproteomics to other technologies 254
  • Figure 9-1: A scheme of proteomics applications in CNS drug discovery and development 299
  • Figure 10-1: Types of companies involved in proteomics collaborations 309
  • Figure 10-2: Types of collaborations: R & D, licensing or marketing 309
  • Figure 10-3: Proteomics collaborations according to application areas 310
  • Figure 10-4: Proteomics collaborations according to technologies 310
  • Figure 10-5: Unmet needs in proteomics 316
  • Figure 11-1: A scheme of the role of proteomics in personalized management of cancer 334

Part II

11. Companies involved in developing proteomics 4

  • Introduction 4
  • Profiles of selected companies 10
  • Collaborations 249

Tables

  • Table 11-1: Companies with proteomics as the main activity/service 4
  • Table 11-2: Selected companies with equipment and laboratory services for proteomics 6
  • Table 11-3: Biotechnology and drug discovery companies involved in proteomics 6
  • Table 11-4: Bioinformatics companies involved in proteomics 8
  • Table 11-5: Biopharmaeutical companies with in-house proteomics technology 9
  • Table 11-6: Major players in proteomics 9
  • Table 10-7: Selected collaborations of companies in the area of proteomics 249
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