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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07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

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 44 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 223 of these are profiled in the report with 460 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 2013 and are projected to years 2018 and 2023. 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 23
  • Decoding of mRNA by the ribosome 24
  • Genes 24
  • Alternative splicing 24
  • Transcription 25
  • Gene regulation 26
  • Gene expression 26
  • Chromatin 27
  • Golgi complex 27
  • Proteins 28
  • Spliceosome 28
  • Functions of proteins 28
  • Inter-relationship of protein, mRNA and DNA 29
  • Proteomics 30
  • Mitochondrial proteome 31
  • S-nitrosoproteins in mitochondria 32
  • Proteomics and genomics 32
  • Classification of proteomics 35
  • Levels of functional genomics and various "omics" 35
  • Glycoproteomics 35
  • Transcriptomics 36
  • Metabolomics 36
  • Cytomics 36
  • Phenomics 36
  • Impact of the genetic factors on the human proteome 37
  • Proteomics and systems biology 37
  • Functional synthetic proteins 38

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
  • Electrospray ionization 48
  • Desorption electrospray ionization MS 50
  • Mirosaic 3500 MiD 50
  • Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry 50
  • Cryogenic MALDI- Fourier Transform Mass Spectrometry 52
  • Stable-isotope-dilution tandem mass spectrometry 52
  • HUPO Gold MS Protein Standard 52
  • Companies involved in mass spectrometry 53
  • High performance liquid chromatography 53
  • 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 55
  • Quantification of low abundance proteins 56
  • SDS-PAGE 56
  • Antibodies and proteomics 56
  • 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 58
  • C-terminal peptide analysis 59
  • 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 63
  • 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 66
  • Nanoelectrospray ionization 67
  • Nanoproteomics for discovery of protein biomarkers in the blood 67
  • QD-protein nanoassembly 67
  • Nanoparticle barcodes 68
  • Biobarcode assay for proteins 68
  • Nanopore-based protein sequencing 69
  • Nanoscale protein analysis 69
  • Nanoscale mechanism for protein engineering 70
  • Nanotube electronic biosensor 70
  • Nanotube-vesicle networks for study of membrane proteins 71
  • Nanowire transistor for the detection of protein-protein interactions 71
  • Qdot-nanocrystals 71
  • Resonance Light Scattering technology 72
  • Study of single membrane proteins at subnanometer resolution 72
  • Protein expression profiling 72
  • 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
  • Bacterial protein interaction studies for assigning function 77
  • Bioluminescence Resonance Energy Transfer 77
  • Computational prediction of interactions 77
  • Detection Enhanced Ubiquitin Split Protein Sensor technology 78
  • Double Switch technology 78
  • Fluorescence Resonance Energy Transfer 78
  • In vivo study of protein-protein interactions 79
  • In vitro study of protein-protein interactions 79
  • Interactome 79
  • Membrane 1-hybrid method 80
  • Phage display 81
  • Protein affinity chromatography 81
  • Protein-fragment complementation system 81
  • Yeast 2-hybrid system 81
  • Companies with technologies for protein-protein interaction studies 82
  • Protein-DNA interaction 83
  • Determination of protein structure 84
  • X-Ray crystallography 84
  • Nuclear magnetic resonance 85
  • Electron spin resonance 85
  • 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 88
  • Isotope-coded affinity tag peptide labeling 89
  • Differential Proteomic Panning 89
  • Cell map proteomics 90
  • Topological proteomics 90
  • Organelle or subcellular proteomics 91
  • Nucleolar proteomics 91
  • Glycoproteomic technologies 92
  • High-sensitivity glycoprotein analysis 92
  • Fluorescent in vivo imaging of glycoproteins 92
  • Integrated approaches for protein characterization 92
  • Imaging mass spectrometry 93
  • IMS technologies 93
  • Applications of IMS 94
  • The protein microscope 94
  • Tag-Mass IMS 94
  • Automation and robotics in proteomics 95
  • Western blot 95
  • Limitations of WB 95
  • 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 98
  • 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 100
  • 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
  • Human proteome map 131
  • International Protein Index 131
  • MS-based draft of the human proteome 131
  • Protein Structure Initiative - Structural Genomics Knowledgebase 131
  • Protein Warehouse Database 132
  • Protein Data Bank 132
  • Repository for raw data from proteomics MS 132
  • Universal Protein Resource 133
  • Protein interaction databases 133
  • Biomolecular Interaction Network Database 134
  • ENCODE 134
  • Functional Genomics Consortium 135
  • Human Proteinpedia 135
  • ProteinCenter 135
  • Databases of the National Center for Biotechnology Information 136
  • Bioinformatics for protein identification 136
  • Application of bioinformatics in functional proteomics 136
  • Use of bioinformatics in protein sequencing 137
  • Bottom-up protein sequencing 138
  • Top-down protein sequencing 139
  • Protein structural database approach to drug design 139
  • Bioinformatics for high-throughput proteomics 139
  • Bioinformatics for protein-protein interactions 140
  • Companies with bioinformatic tools for proteomics 141

5. Research in Proteomics 144

  • Introduction 144
  • Applications of proteomics in biological research 144
  • Identification of novel human genes by comparative proteomics 144
  • Study of relationship between genes and proteins 145
  • Characterization of histone codes 145
  • Structural genomics or structural proteomics 146
  • Protein Structure Factory 147
  • Protein Structure Initiative 147
  • Studies on protein structure at Argonne National Laboratory 148
  • Structural Genomics Consortium 148
  • Protein knockout 149
  • Antisense approach and proteomics 149
  • RNAi and protein knockout 149
  • Total knockout of cellular proteins 150
  • Ribozymes and proteomics 150
  • Single molecule proteomics 150
  • Single-molecule photon stamping spectroscopy 150
  • Single nucleotide polymorphism determination by TOF-MS 151
  • Application of proteomic technologies in systems biology 151
  • Signaling pathways and proteomics 152
  • Kinomics 152
  • Combinatorial RNAi for quantitative protein network analysis 152
  • Proteomics in neuroscience research 153
  • Stem cell proteomics 153
  • Comparative proteomic analysis of somatic cells, iPSCs and ESCs 154
  • hESC phosphoproteome 154
  • Proteomic studies of mesenchymal stem cells 154
  • Proteomics of neural stem cells 155
  • Proteome Biology of Stem Cells Initiative 155
  • Proteomic analysis of the cell cycle 156
  • Nitric oxide and proteomics 156
  • A proteomic method for identification of cysteine S-nitrosylation sites 156
  • Study of the nitroproteome 157
  • Study of the phosphoproteome 157
  • Study of the mitochondrial proteome 158
  • Proteomic technologies for study of mitochondrial proteomics 158
  • Cryptome 159
  • Study of protein transport in health and disease 159
  • Ancient proteomics 159
  • Proteomics research in the academic sector 160
  • Netherlands Proteins@Work 162
  • ProteomeBinders initiative 162
  • Rutgers University's Center for Integrative Proteomics Research 162
  • Vanderbilt University's Center for Proteomics and Drug Actions 163

6. Pharmaceutical Applications of Proteomics 164

  • Introduction 164
  • Current drug discovery process and its limitations 164
  • Role of omics in drug discovery 165
  • Genomics-based drug discovery 165
  • Metabolomics technologies for drug discovery 166
  • Role of metabonomics in drug discovery 166
  • Basis of proteomics approach to drug discovery 167
  • Proteins and drug action 167
  • Transcription-aided drug design 168
  • Role of proteomic technologies in drug discovery 168
  • Liquid chromatography-based drug discovery 169
  • Capture compound mass spectrometry 170
  • Protein-expression mapping by 2DGE 170
  • Protein-protein interactions and drug discovery 170
  • Role of MALDI mass spectrometry in drug discovery 170
  • Structural proteomics and drug discovery 171
  • Tissue imaging mass spectrometry 172
  • Oxford Genome Anatomy Project 173
  • Proteins as drug targets 173
  • Ligands to capture the purine binding proteome 174
  • Chemical probes to interrogate key protein families for drug discovery 174
  • Global proteomics for pharmacodynamics 175
  • CellCarta® proteomics platform 175
  • ZeptoMARK™ protein profiling system 176
  • Role of proteomics in targeting disease pathways 176
  • Dynamic proteomics 176
  • Identification of protein kinases as drug targets 177
  • Mechanisms of action of kinase inhibitors 177
  • G-protein coupled receptors as drug targets 178
  • Methods of study of GPCRs 178
  • Cell-based assays for GPCR 178
  • Companies involved in GPCR-based drug discovery 179
  • GPCR localization database 180
  • Matrix metalloproteases as drug targets 180
  • PDZ proteins as drug targets 181
  • Proteasome as drug target 181
  • Serine hydrolases as drug targets 182
  • Targeting mTOR signaling pathway 182
  • Targeting caspase-8 for anticancer therapeutics 183
  • Bioinformatic analysis of proteomics data for drug discovery 184
  • Drug design based on structural proteomics 184
  • Protein crystallography for determining 3D structure of proteins 184
  • Automated 3D protein modeling 185
  • Drug targeting of flexible dynamic proteins 185
  • Companies involved in structure-based drug-design 185
  • Integration of genomics and proteomics for drug discovery 186
  • Ligand-receptor binding 187
  • Role of proteomics in study of ligand-receptor binding 187
  • Measuring drug binding of proteins 188
  • Aptamer protein binding 188
  • Systematic Evolution of Ligands by Exponential Enrichment 188
  • Aptamers and high-throughput screening 189
  • Nucleic Acid Biotools 189
  • Aptamer beacons 190
  • Peptide aptamers 190
  • Riboreporters for drug discovery 190
  • Target identification and validation 191
  • Application of mass spectrometry for target identification 191
  • Gene knockout and gene suppression for validating protein targets 191
  • Laser-mediated protein knockout for target validation 192
  • Integrated proteomics for drug discovery 192
  • High-throughput proteomics 193
  • Companies involved in high-throughput proteomics 193
  • Drug discovery through protein-protein interaction studies 194
  • Protein-protein interaction as basis for drug target identification 194
  • Protein-PCNA interaction as basis for drug design 195
  • Two-hybrid protein interaction technology for target identification 195
  • Biosensors for detection of small molecule-protein interactions 196
  • Protein-protein interaction maps 196
  • ProNet (Myriad Genetics) 196
  • Hybrigenics' maps of protein-protein interactions 197
  • CellZome's functional map of protein-protein interactions 197
  • Mapping of protein-protein interactions by mass spectrometry 198
  • Protein interaction map of Drosophila melanogaster 198
  • Protein-interaction map of Wellcome Trust Sanger Institute 198
  • Protein-protein interactions as targets for therapeutic intervention 199
  • Inhibition of protein-protein interactions by peptide aptamers 199
  • Selective disruption of proteins by small molecules 199
  • Post-genomic combinatorial biology approach 200
  • Differential proteomics 200
  • Shotgun proteomics 201
  • Chemogenomics/chemoproteomics for drug discovery 201
  • Chemoproteomics-based drug discovery 202
  • Companies involved in chemogenomics/chemoproteomics 203
  • Activity-based proteomics 204
  • Locus Discovery technology 204
  • Automated ligand identification system 205
  • Expression proteomics: protein level quantification 206
  • Role of phage antibody libraries in target discovery 206
  • Analysis of posttranslational modification of proteins by MS 206
  • Phosphoproteomics for drug discovery 207
  • Application of glycoproteomics for drug discovery 207
  • Role of carbohydrates in proteomics 207
  • Challenges of glycoproteomics 208
  • Companies involved in glycoproteomics 208
  • Role of protein microarrays/ biochips for drug discovery 209
  • Protein microarrays vs DNA microarrays for high-throughput screening 209
  • BIA-MS biochip for protein-protein interactions 210
  • ProteinChip with Surface Enhanced Neat Desorption 210
  • Protein-domains microarrays 210
  • Some limitations of protein biochips 211
  • Concluding remarks about role of proteomics in drug discovery 211
  • RNA versus protein profiling as guide to drug development 212
  • RNA as drug target 212
  • Combination of RNA and protein profiling 213
  • RNA binding proteins 213
  • Toxicoproteomics 213
  • Hepatotoxicity 213
  • Nephrotoxicity 214
  • Cardiotoxicity 215
  • Neurotoxicity 215
  • Protein/peptide therapeutics 215
  • Alphabody technology for improving protein therapeutics 215
  • Peptide-based drugs 216
  • Phylomer® peptides 216
  • Cryptein-based therapeutics 216
  • Synthetic proteins and peptides as pharmaceuticals 217
  • Genetic immunization and proteomics 218
  • Proteomics and gene therapy 218
  • Role of proteomics in clinical drug development 219
  • Pharmacoproteomics 219
  • Role of proteomics in clinical drug safety 219

7. Application of Proteomics in Human Healthcare 222

  • Introduction 222
  • Clinical proteomics 223
  • Definition and standards 223
  • Vermillion's Clinical Proteomics Program 223
  • Pathophysiology of human diseases 224
  • Diseases due to misfolding of proteins 224
  • Mechanism of protein folding 225
  • Nanoproteomics for study of misfolded proteins 226
  • Therapies for protein misfolding 226
  • Intermediate filament proteins 227
  • Significance of mitochondrial proteome in human disease 228
  • Proteome of Saccharomyces cerevisiae mitochondria 228
  • Rat mitochondrial proteome 228
  • Proteomic approaches to biomarker identification 229
  • The ideal biomarker 229
  • Proteomic technologies for biomarker discovery 229
  • MALDI mass spectrometry for biomarker discovery 230
  • BAMF™ Technology 230
  • Protein biochips/microarrays and biomarkers 231
  • Affinity proteomics for discovery of biomarkers 231
  • Antibody array-based biomarker discovery 231
  • Discovery of biomarkers by MAb microarray profiling 232
  • Tumor-specific serum peptidome patterns 232
  • Search for protein biomarkers in body fluids 233
  • Challenges and strategies for discovey of protein biomarkers in plasma 233
  • 3-D structure of CD38 as a biomarker 234
  • BD™ Free Flow Electrophoresis System 234
  • Isotope tags for relative and absolute quantification 234
  • N-terminal peptide isolation from human plasma 235
  • Plasma protein microparticles as biomarkers 235
  • Proteome partitioning 236
  • SISCAPA method for quantitating proteins and peptides in plasma 236
  • Stable isotope tagging methods 236
  • Technology to measure both the identity and size of the biomarker 237
  • Biomarkers in the urinary proteome 237
  • Application of proteomics in molecular diagnosis 238
  • Proximity ligation assay 239
  • Protein patterns 239
  • Proteomic tests on body fluids 239
  • Cyclical amplification of proteins 241
  • Applications of proteomics in infections 241
  • MALDI-TOF MS for microbial identification 241
  • Role of proteomics in virology 242
  • Interaction of proteins with viruses 242
  • Quantitative temporal viromics 243
  • Role of proteomics in bacteriology 243
  • Epidemiology of bacterial infections 243
  • Proteomic approach to bacterial pathogenesis 244
  • Vaccines for bacterial infections 244
  • Protein profiles associated with bacterial drug resistance 245
  • Analyses of the parasite proteome 245
  • Application of proteomics in cystic fibrosis 245
  • Proteomics of cardiovascular diseases 246
  • Pathomechanism of cardiovascular diseases 246
  • Protein misfolding in cardiac dysfunction 246
  • Study of cardiac mitochondrial proteome in myocardial ischemia 247
  • Cardiac protein databases 247
  • Proteomics of dilated cardiomyopathy and heart failure 247
  • Proteomic biomarkers of cardiovascular diseases 248
  • Role of proteomics in cardioprotection 248
  • Role of proteomics in heart transplantation 248
  • Future of application of proteomics in cardiology 249
  • Proteomic technologies for research in pulmonary disorders 249
  • Application of proteomics in renal disorders 250
  • Diagnosis of renal disorders 251
  • Proteomic biomarkers of acute kidney injury 251
  • Cystatin C as biomarker of glomerular filtration rate 251
  • Protein biomarkers of nephritis 251
  • Proteomics and kidney stones 252
  • Proteomics of eye disorders 252
  • Proteomics of cataract 253
  • Proteomics of diabetic retinopathy 253
  • Retinal dystrophies 253
  • Use of proteomics in inner ear disorders 254
  • Use of proteomics in aging research 254
  • Alteration of glycoproteins during aging 255
  • Removal of altered cellular proteins in aging 255
  • Study of the role of Parkin in modulating aging 255
  • Proteomics and nutrition 256

8. Oncoproteomics 258

  • Introduction 258
  • Proteomic technologies for study of cancer 259
  • Application of CellCarta technology for oncology 259
  • Accentuation of differentially expressed proteins using phage technology 259
  • Cancer tissue proteomics 259
  • Dynamic cell proteomics in response to a drug 260
  • Desorption electrospray ionization for cancer diagnosis 260
  • Id proteins as targets for cancer therapy 261
  • Identification of oncogenic tyrosine kinases using phosphoproteomics 261
  • Laser capture microdissection technology and cancer proteomics 261
  • Mass spectrometry for identification of oncogenic chimeric proteins 262
  • Proteomic analysis of cancer cell mitochondria 262
  • Proteomic study of p53 263
  • Human Tumor Gene Index 263
  • Integration of cancer genomics and proteomics 263
  • Role of proteomics in study of cancer stem cell biology 264
  • Single-cell protein expression analysis by microfluidic techniques 264
  • Use of proteomics in cancers of various organ systems 264
  • Proteomics of brain tumors 264
  • Malignant glial tumors 264
  • Meningiomas 265
  • DESI-MS for intraoperative diagnosis of brain tumors 265
  • Proteomics of breast cancer 266
  • Integration of proteomic and genomic data for breast cancer 267
  • Proteomics of colorectal cancer 268
  • Proteomics of esophageal cancer 268
  • Proteomics of hepatic cancer 269
  • Proteomics of leukemia 269
  • Proteomics of lung cancer 270
  • Proteomics of pancreatic cancer 271
  • Proteomics of prostate cancer 271
  • Proteomics of renal cancer 272
  • Diagnostic use of cancer biomarkers 272
  • Proteomic technologies for tumor biomarkers 273
  • Nuclear matrix proteins (NMPs) 273
  • Antiannexins as tumor markers in lung cancer 274
  • NCI's Network of Clinical Proteomic Technology Centers 274
  • Proteomics and tumor immunology 275
  • Proteomics and study of tumor invasiveness 276
  • Anticancer drug discovery and development 276
  • Kinase-targeted drug discovery in oncology 276
  • Anticancer drug targeting: functional proteomics screen of proteases 277
  • Small molecule inhibitors of cancer-related proteins 277
  • Role of proteomics in studying drug resistance in cancer 277
  • Future prospects of oncoproteomics 278
  • Clinical Proteomic Tumor Analysis Consortium 278
  • Companies involved in application of proteomics to oncology 279

9. Neuroproteomics 282

  • Introduction 282
  • Application of proteomics for the study of nervous system 282
  • Proteomics of prion diseases 283
  • Normal function of prions in the brain 283
  • Diseases due to pathological prion protein 283
  • Transmissible spongiform encephalopathies 284
  • Creutzfeld-Jakob disease 284
  • Bovine spongiform encephalopathy 284
  • Variant Creutzfeldt-Jakob disease 285
  • Protein misfolding and neurodegenerative disorders 285
  • Ion channel link for protein-misfolding disease 285
  • Detection of misfolded proteins 285
  • Neurodegenerative disorders with protein abnormalities 286
  • Alzheimer disease 288
  • Common denominators of Alzheimer and prion diseases 288
  • Parkinson disease 289
  • Amyotrophic lateral sclerosis 289
  • Proteomics and glutamate repeat disorders 290
  • Proteomics and Huntington's disease 290
  • Proteomics and demyelinating diseases 291
  • Proteomics of neurogenetic disorders 291
  • Fabry disease 291
  • GM1 gangliosidosis 292
  • Quantitative proteomics and familial hemiplegic migraine 292
  • Proteomics of spinal muscular atrophy 293
  • Proteomics of CNS trauma 293
  • Proteomics of traumatic brain injury 293
  • Chronic traumatic encephalopathy and ALS 294
  • Proteomics of cerebrovascular disease 294
  • Proteomics of CNS aging 295
  • Protein aggregation as a bimarker of aging 295
  • Neuroproteomics of psychiatric disorders 296
  • Neuroproteomic of cocaine addiction 296
  • Neurodiagnostics based on proteomics 297
  • Disease-specific proteins in the cerebrospinal fluid 297
  • Tau proteins 298
  • CNS tissue proteomics 298
  • Diagnosis of CNS disorders by examination of proteins in urine 300
  • Diagnosis of CNS disorders by examination of proteins in the blood 300
  • Serum pNF-H as biomarker of CNS damage 301
  • Proteomics of BBB 301
  • Future prospects of neuroproteomics in neurology 301
  • HUPO's Pilot Brain Proteome Project 303

10. Proteomics Markets 304

  • Introduction 304
  • Potential markets for proteomic technologies 304
  • Bioinformatics markets for proteomics 305
  • Markets for protein separation technologies 305
  • Markets for 2D gel electrophoresis 305
  • Market trends in protein separation technolgies 306
  • Protein purification markets 306
  • Mass spectrometry markets 306
  • Markets for MALDI for drug discovery 307
  • Markets for nuclear magnetic resonance spectroscopy 307
  • Market for structure-based drug design 307
  • Markets for protein biomarkers 308
  • Markets for cell-based protein assays 308
  • Protein biochip markets 308
  • Western blot markets 308
  • Geographical distribution of proteomics technologies markets 309
  • Business and strategic considerations 309
  • Cost of protein structure determination 309
  • Opinion surveys of the scientist consumers of proteomic technologies 309
  • Opinions on mass spectrometry 309
  • Opinions on bioinformatics and proteomic databases 310
  • Systems for in vivo study of protein-protein interactions 310
  • Perceptions of the value of protein biochip/microfluidic systems 310
  • Small versus big companies 310
  • Expansion in proteomics according to area of application 311
  • Growth trends in cell-based protein assay market 311
  • Challenges for development of cell-based protein assays 311
  • Future trends and prospects of cell-based protein assays 312
  • Strategic collaborations 312
  • Analysis of proteomics collaborations according to types of companies 312
  • Types of proteomic collaborations 313
  • Proteomics collaborations according to application areas 313
  • Analysis of proteomics collaborations: types of technologies 314
  • Collaborations based on protein biochip technology 314
  • Concluding remarks about proteomic collaborations 315
  • Proteomic patents 315
  • Market drivers in proteomics 316
  • Needs of the pharmaceutical industry 316
  • Need for outsourcing proteomic technologies 316
  • Funding of proteomic companies and research 316
  • Technical advances in proteomics 317
  • Changing trends in healthcare in future 317
  • Challenges facing proteomics 317
  • Magnitude and complexity of the task 317
  • Technical challenges 318
  • Limitations of proteomics 318
  • Limitations of 2DGE 318
  • Limitations of mass spectrometry techniques 318
  • Complexity of the pharmaceutical proteomics 319
  • Unmet needs in proteomics 319

11. Future of Proteomics 322

  • Genomics to proteomics 322
  • Faster technologies 322
  • FLEXGene repository 322
  • Need for new proteomic technologies 323
  • Emerging proteomic technologies 324
  • Detection of alternative protein isoforms 324
  • Direct protein identification in large genomes by mass spectrometry 324
  • Proteome identification kits with stacked membranes 324
  • Vacuum deposition interface 325
  • In vitro protein biosynthesis 325
  • Proteome mining with adenosine triphosphate 325
  • Proteome-scale purification of human proteins from bacteria 325
  • Proteostasis network 326
  • Cytoproteomics 326
  • Subcellular proteomics 326
  • Individual cell proteomics 327
  • Live cell proteomics 327
  • Fluorescent proteins for live-cell imaging 328
  • Membrane proteomics 328
  • Identification of membrane proteins by tandem MS of protein ions 328
  • Solid state NMR for study of nanocrystalline membrane proteins 329
  • Multiplex proteomics 329
  • High-throughput for proteomics 329
  • Future directions for protein biochip application 330
  • Bioinformatics for proteomics 330
  • High-Throughput Crystallography Consortium 330
  • Study of protein folding by IBM's Blue Gene 331
  • Study of proteins by atomic force microscopy 331
  • Population proteomics 331
  • Comparative proteome analysis 332
  • Human Proteome Organization 332
  • Cell-based Human Proteome Project 333
  • Human Salivary Proteome 333
  • Academic-commercial collaborations in proteomics 334
  • Indiana Centers for Applied Protein Sciences 334
  • Role of proteomics in the healthcare of the future 334
  • Proteomics and molecular medicine 334
  • Proteodiagnostics 335
  • Proteomics and personalized medicine 335
  • Targeting the ubiquitin pathway for personalized therapy of cancer 336
  • Protein patterns and personalized medicine 336
  • Personalizing interferon therapy of hepatitis C virus 338
  • Protein biochips and personalized medicine 338
  • Combination of diagnostics and therapeutics 339
  • Future prospects 339

12. References 340

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 30
  • 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 53
  • 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 100
  • 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 134
  • Table 4-3: Bioinformatic tools for proteomics from academic sources 140
  • Table 4-4: Selected companies involved in bioinformatics for proteomics 141
  • Table 5-1: Applications of proteomics in basic biological research 144
  • Table 5-2: A sampling of proteomics research projects in academic institutions 160
  • Table 6-1: Pharmaceutical applications of proteomics 164
  • Table 6-2: Selected companies relevant to MALDI-MS for drug discovery 171
  • Table 6-3: Selected companies involved in GPCR-based drug discovery 179
  • Table 6-4: Companies involved in drug design based on structural proteomics 186
  • Table 6-5: Proteomic companies with high-throughput protein expression technologies 193
  • Table 6-6: Selected companies involved in chemogenomics/chemoproteomics 203
  • Table 6-7: Companies involved in glycoproteomic technologies 209
  • Table 7-1: Applications of proteomics in human healthcare 222
  • Table 7-2: Eye disorders and proteomic approaches 252
  • Table 8-1: Companies involved in applications of proteomics to oncology 279
  • Table 9-1: Neurodegenerative diseases with underlying protein abnormality 286
  • Table 9-2: Disease-specific proteins in the cerebrospinal fluid of patients 297
  • Table 10-1: Potential markets for proteomic technologies 2013-2023 304
  • Table 10-2: 2013 revenues of major companies from protein separation technologies 305
  • Table 10-3: Geographical distribution of markets for proteomic technologies 2013-2023 309
  • Table 11-1: Role of proteomics in personalizing strategies for cancer therapy 336

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. 33
  • 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) 51
  • Figure 2-5: Scheme of bio-bar-code assay 69
  • Figure 2-6: A diagrammatic presentation of yeast 2-hybrid system 82
  • 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 138
  • Figure 6-1: Drug discovery process 165
  • Figure 6-2: Regulatory changes induced by drugs and implemented at the proteins level. 168
  • Figure 6-3: Relation of proteome to genome, diseases and drugs 169
  • Figure 6-4: The mTOR pathways 183
  • Figure 6-5: Steps in shotgun proteomics 201
  • Figure 6-6: Chemogenomic approach to drug discovery (3-Dimensional Pharmaceuticals) 202
  • Figure 8-1: Relation of oncoproteomics to other technologies 258
  • Figure 9-1: A scheme of proteomics applications in CNS drug discovery and development 303
  • Figure 10-1: Types of companies involved in proteomics collaborations 313
  • Figure 10-2: Types of collaborations: R & D, licensing or marketing 313
  • Figure 10-3: Proteomics collaborations according to application areas 314
  • Figure 10-4: Proteomics collaborations according to technologies 314
  • Figure 10-5: Unmet needs in proteomics 320
  • Figure 11-1: A scheme of the role of proteomics in personalized management of cancer 338

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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