The postgenomic age: characterization of proteomes.

Global analysis of biological systems is becoming increasingly feasible as technologies that facilitate genome-wide analyses of gene expression are developed. Proteomics is the global analysis of expressed proteins (including posttranslational modifications) and seeks to establish the relationship between genome sequence, expressed proteins, protein-protein interactions, and cell and tissue phenotype. While the relative abundance of transcripts can be quantified using gene expression microarrays, the identification and quantitation of expressed proteins is more challenging. Nevertheless, the potential payoff for global protein analyses is immense because identification of distinctive protein signatures associated with cell function may provide novel therapeutic targets, molecular markers of disease, and increased understanding of determinants of cell phenotype. The challenges and promises of applications of established and emerging proteome strategies to detect and quantify differentially expressed proteins in culture cells are discussed.

[1]  O. Vorm,et al.  Identification of precursor forms of free prostate-specific antigen in serum of prostate cancer patients by immunosorption and mass spectrometry. , 2001, Cancer research.

[2]  F Gharahdaghi,et al.  Mass spectrometric identification of proteins from silver‐stained polyacrylamide gel: A method for the removal of silver ions to enhance sensitivity , 1999, Electrophoresis.

[3]  P. Cohen,et al.  Signal integration at the level of protein kinases, protein phosphatases and their substrates. , 1992, Trends in biochemical sciences.

[4]  H. Davies,et al.  Profiling of amyloid beta peptide variants using SELDI Protein Chip arrays. , 1999, BioTechniques.

[5]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[6]  W. Blackstock,et al.  Proteomics: quantitative and physical mapping of cellular proteins. , 1999, Trends in biotechnology.

[7]  T. Hunter,et al.  Phosphopeptide mapping and phosphoamino acid analysis by electrophoresis and chromatography on thin‐layer cellulose plates , 1994, Electrophoresis.

[8]  D. Hochstrasser,et al.  From Proteins to Proteomes: Large Scale Protein Identification by Two-Dimensional Electrophoresis and Arnino Acid Analysis , 1996, Bio/Technology.

[9]  D. Hochstrasser,et al.  High-resolution, IPG-based, mini two-dimensional gel electrophoresis. , 1999, Methods in molecular biology.

[10]  E. Müller,et al.  Identification of human myocardial proteins separated by two‐dimensional electrophoresis with matrix‐assisted laser desorption/ionization mass spectrometry , 1996, Electrophoresis.

[11]  B. Austen,et al.  The use of Seldi ProteinChip™ Arrays to monitor production of Alzheimer's β‐amyloid in transfected cells , 2000 .

[12]  H. Ge,et al.  UPA, a universal protein array system for quantitative detection of protein-protein, protein-DNA, protein-RNA and protein-ligand interactions. , 2000, Nucleic acids research.

[13]  K. Gevaert,et al.  A fast and convenient MALDI-MS based proteomic approach: identification of components scaffolded by the actin cytoskeleton of activated human thrombocytes. , 2000, Journal of biotechnology.

[14]  M. Perrot,et al.  Two‐dimensional gel protein database of Saccharomyces cerevisiae , 1996, Electrophoresis.

[15]  R. Angeletti Proteins : analysis and design , 1998 .

[16]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[17]  Uwe Claussen,et al.  Mass spectrometry meets chip technology: A new proteomic tool in cancer research? , 2001, Electrophoresis.

[18]  S. Schreiber,et al.  Printing proteins as microarrays for high-throughput function determination. , 2000, Science.

[19]  James L. Winkler,et al.  Accessing Genetic Information with High-Density DNA Arrays , 1996, Science.

[20]  H. Lehrach,et al.  Analysis of the mouse proteome. (I) Brain proteins: Separation by two‐dimensional electrophoresis and identification by mass spectrometry and genetic variation , 1999, Electrophoresis.

[21]  David E. Misek,et al.  Profiling Changes in Gene Expression during Differentiation and Maturation of Monocyte-derived Dendritic Cells Using Both Oligonucleotide Microarrays and Proteomics* , 2001, The Journal of Biological Chemistry.

[22]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[23]  S. Gygi,et al.  Correlation between Protein and mRNA Abundance in Yeast , 1999, Molecular and Cellular Biology.

[24]  J. Hettick,et al.  Improvement of resolution, mass accuracy, and reproducibility in reflected mode DE-MALDI-TOF analysis of DNA using fast evaporation--overlayer sample preparations. , 2000, Analytical chemistry.

[25]  A. Shevchenko,et al.  Two‐dimensional gel protein database of Saccharomyces cerevisiae (update 1999) , 1999, Electrophoresis.

[26]  P. Cao,et al.  Mapping the phosphorylation sites of proteins using on-line immobilized metal affinity chromatography/capillary electrophoresis/electrospray ionization multiple stage tandem mass spectrometry. , 2000, Rapid communications in mass spectrometry : RCM.

[27]  T Voss,et al.  Observations on the reproducibility and matching efficiency of two‐dimensional electrophoresis gels: Consequences for comprehensive data analysis , 2000, Electrophoresis.

[28]  A. Rivett,et al.  Phosphorylation of ATPase subunits of the 26S proteasome , 1998, FEBS letters.

[29]  C. Watanabe,et al.  Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. Hochstrasser,et al.  Preparation and solubilization of body fluids for 2-D. , 1999, Methods in molecular biology.

[31]  B. Chait,et al.  Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome , 2001, Nature Biotechnology.

[32]  M. Vingron,et al.  Improved sensitivity proteomics by postharvest alkylation and radioactive labeling of proteins , 2000, Electrophoresis.

[33]  J. Yates,et al.  Coronin Promotes the Rapid Assembly and Cross-linking of Actin Filaments and May Link the Actin and Microtubule Cytoskeletons in Yeast , 1999, The Journal of cell biology.

[34]  J. Yates,et al.  Large-scale analysis of the yeast proteome by multidimensional protein identification technology , 2001, Nature Biotechnology.

[35]  M F Bean,et al.  Collisional fragmentation of glycopeptides by electrospray ionization LC/MS and LC/MS/MS: methods for selective detection of glycopeptides in protein digests. , 1993, Analytical chemistry.

[36]  J. D. Vos,et al.  Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays. , 2001, Blood.

[37]  Richard D. Smith,et al.  Utility of accurate mass tags for proteome-wide protein identification. , 2000, Analytical chemistry.

[38]  Joachim Klose,et al.  Two‐dimensional electrophoresis of proteins: An updated protocol and implications for a functional analysis of the genome , 1995, Electrophoresis.

[39]  Richard D. Smith,et al.  Phosphoprotein isotope-coded affinity tag approach for isolating and quantitating phosphopeptides in proteome-wide analyses. , 2001, Analytical chemistry.

[40]  C. G. Edmonds,et al.  Tandem mass spectrometry of very large molecules: serum albumin sequence information from multiply charged ions formed by electrospray ionization. , 1991, Analytical chemistry.

[41]  T. Hunkapiller,et al.  Peptide mass maps: a highly informative approach to protein identification. , 1993, Analytical biochemistry.

[42]  S. Gygi,et al.  Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[43]  P. Højrup,et al.  Use of mass spectrometric molecular weight information to identify proteins in sequence databases. , 1993, Biological mass spectrometry.

[44]  E Carafoli,et al.  Protein identification in DNA databases by peptide mass fingerprinting , 1994, Protein science : a publication of the Protein Society.

[45]  P. Brown,et al.  A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. , 1996, Genome research.

[46]  Mary F. Lopez,et al.  High‐throughput profiling of the mitochondrial proteome using affinity fractionation and automation , 2000, Electrophoresis.

[47]  J. Yates,et al.  Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. , 2000, Molecular biology of the cell.

[48]  M. Mann,et al.  Identification of the receptor component of the IκBα–ubiquitin ligase , 1998, Nature.

[49]  T. Veenstra,et al.  Quantitative analysis of bacterial and mammalian proteomes using a combination of cysteine affinity tags and 15N-metabolic labeling. , 2001, Analytical chemistry.

[50]  T. Arendt,et al.  Distribution of isoforms of the microtubule‐associated protein tau in grey and white matter areas of human brain: A two‐dimensional gelelectrophoretic analysis , 1996, FEBS letters.

[51]  A. Tomlinson,et al.  Systematic development of on-line membrane preconcentration-capillary electrophoresis-mass spectrometry for the analysis of peptide mixtures. , 1995, Journal of capillary electrophoresis.

[52]  R D Appel,et al.  Melanie II – a third‐generation software package for analysis of two‐dimensional electrophoresis images: I. Features and user interface , 1997, Electrophoresis.

[53]  D. Lockhart,et al.  Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[54]  Richard D. Smith,et al.  Two-dimensional electrophoretic/chromatographic separations combined with electrospray ionization FTICR mass spectrometry for high throughput proteome analysis , 2000 .

[55]  R D Appel,et al.  Melanie II – a third‐generation software package for analysis of two‐dimensional electrophoresis images: II. Algorithms , 1997, Electrophoresis.

[56]  K P Pleissner,et al.  Proteomics in human disease: Cancer, heart and infectious diseases , 1999, Electrophoresis.

[57]  F. Cross,et al.  Accurate quantitation of protein expression and site-specific phosphorylation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[58]  H. Davies,et al.  Tissue-specific microdissection coupled with ProteinChip array technologies: applications in cancer research. , 2000, BioTechniques.

[59]  K. Williams,et al.  UV-induced melanoma cell lines and their potential for proteome analysis: a review. , 1998, The Journal of experimental zoology.

[60]  E. Petricoin,et al.  Proteomic analysis of laser capture microdissected human prostate cancer and in vitro prostate cell lines , 2000, Electrophoresis.

[61]  J. Lutterbaugh,et al.  Detection of aberrantly methylated hMLH1 promoter DNA in the serum of patients with microsatellite unstable colon cancer. , 2001, Cancer research.

[62]  J R Kettman,et al.  Global analysis of gene expression in cells of the immune system I. Analytical limitations in obtaining sequence information on polypeptides in two‐dimensional gel spots , 2000, Electrophoresis.

[63]  J. Stults,et al.  Analysis of peptide synthesis products by electrospray ionization mass spectrometry. , 1997, Methods in enzymology.

[64]  T D Pollard,et al.  The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[65]  S. Gygi,et al.  Quantitative analysis of complex protein mixtures using isotope-coded affinity tags , 1999, Nature Biotechnology.

[66]  J. Yates Mass spectrometry and the age of the proteome. , 1998, Journal of mass spectrometry : JMS.

[67]  Nikola Tolić,et al.  High throughput proteome-wide precision measurements of protein expression using mass spectrometry , 1999 .

[68]  Anders Blomberg,et al.  Interlaboratory reproducibility of yeast protein patterns analyzed by immobilized pH gradient two‐dimensional gel electrophoresis , 1995, Electrophoresis.

[69]  P. Cohen,et al.  The role of protein phosphorylation in neural and hormonal control of cellular activity , 1982, Nature.

[70]  A. Karlsson,et al.  Accurate mass determination of a metabolite of a potential diagnostic imaging drug candidate by high performance liquid chromatography with time-of-flight mass spectrometry. , 1999, Rapid communications in mass spectrometry : RCM.

[71]  T. Pawson,et al.  Signaling through scaffold, anchoring, and adaptor proteins. , 1997, Science.

[72]  Wayne F. Patton,et al.  A comparison of silver stain and SYPRO Ruby Protein Gel Stain with respect to protein detection in two‐dimensional gels and identification by peptide mass profiling , 2000, Electrophoresis.

[73]  S. Hoving,et al.  Towards high performance two‐dimensional gel electrophoresis using ultrazoom gels , 2000, Electrophoresis.

[74]  W. Blackstock,et al.  Proteome research: Complementarity and limitations with respect to the RNA and DNA worlds , 1997, Electrophoresis.

[75]  M. Mann,et al.  Identification of the proteins of the yeast U1 small nuclear ribonucleoprotein complex by mass spectrometry. , 1997, Proceedings of the National Academy of Sciences of the United States of America.