Proteomics: Capacity versus utility

Until recently scientists studied genes or proteins one at a time. With improvements in technology, new tools have become available to study the complex interactions that occur in biological systems. Global studies are required to do this, and these will involve genomic and proteomic approaches. High‐throughput methods are necessary in each case because the number of genes and proteins in even the simplest of organisms are immense. In the developmental phase of genomics, the emphasis was on the generation and assembly of large amounts of nucleic acid sequence data. Proteomics is currently in a phase of technological development and establishment, and demonstrating the capacity for high throughput is a major challenge. However, funding bodies (both in the public and private sector) are increasingly focused on the usefulness of this capacity. Here we review the current state of proteome research in terms of capacity and utility.

[1]  I. Humphery-Smith,et al.  Proteomic ‘contigs’ of Ochrobactrum anthropi, application of extensive pH gradients , 1997, Electrophoresis.

[2]  A. Görg,et al.  Recent developments in two‐dimensional gel electrophoresis with immobilized pH gradients: Wide pH gradients up to pH 12, longer separation distances and simplified procedures , 1999, Electrophoresis.

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

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

[5]  B. Séraphin,et al.  A generic protein purification method for protein complex characterization and proteome exploration , 1999, Nature Biotechnology.

[6]  P. Schrotz-King,et al.  Use of mass spectrometric methods for protein identification in receptor research. , 1999, Journal of Receptor and Signal Transduction Research.

[7]  P. Righetti,et al.  Resolution of Gγ and Aγ foetal haemoglobin tetramers in immobilized pH gradients , 1987 .

[8]  I. Humphery-Smith,et al.  ‘Proteomic contigs’ of Mycobacterium tuberculosis and Mycobacterium bovis (BCG) using novel immobilised pH gradients , 1997, Electrophoresis.

[9]  B K Hayes,et al.  O-GlcNAcylation of key nuclear and cytoskeletal proteins: reciprocity with O-phosphorylation and putative roles in protein multimerization. , 1996, Glycobiology.

[10]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[11]  A. Görg,et al.  Very alkaline immobilized pH gradients for two‐dimensional electrophoresis of ribosomal and nuclear proteins , 1997, Electrophoresis.

[12]  P. James,et al.  Protein identification in the post-genome era: the rapid rise of proteomics , 1997, Quarterly Reviews of Biophysics.

[13]  D F Hochstrasser,et al.  Toward a clinical molecular scanner for proteome research: parallel protein chemical processing before and during western blot. , 1999, Analytical chemistry.

[14]  W. Marasco,et al.  Intracellular antibodies (intrabodies) for gene therapy of infectious diseases. , 1997, Annual review of microbiology.

[15]  N. Packer,et al.  Glycobiology and proteomics: Is mass spectrometry the holy grail? , 1998, Electrophoresis.

[16]  J Barsoum,et al.  Tat-mediated delivery of heterologous proteins into cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. F. Neuwald,et al.  Purification and biochemical characterization of interchromatin granule clusters , 1999, The EMBO journal.

[19]  P. Goodfellow,et al.  DNA microarrays in drug discovery and development , 1999, Nature Genetics.

[20]  L. Spremulli,et al.  Identification of a mammalian mitochondrial homolog of ribosomal protein S7. , 1999, Biochemical and biophysical research communications.

[21]  Peter R. Baker,et al.  Role of accurate mass measurement (+/- 10 ppm) in protein identification strategies employing MS or MS/MS and database searching. , 1999, Analytical chemistry.

[22]  J. Celis,et al.  2D protein electrophoresis: can it be perfected? , 1999, Current opinion in biotechnology.

[23]  W. G. Bryson,et al.  Improved protein solubility in two‐dimensional electrophoresis using tributyl phosphine as reducing agent , 1998, Electrophoresis.

[24]  M. Mann,et al.  Identifying proteins and post-translational modifications by mass spectrometry. , 1998, Current opinion in structural biology.

[25]  C. Gray,et al.  From genome to proteome: Protein map of Haemophilus influenzae , 1997, Electrophoresis.

[26]  R. Fleischmann,et al.  Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. , 1995, Science.

[27]  T. Keough,et al.  A method for high-sensitivity peptide sequencing using postsource decay matrix-assisted laser desorption ionization mass spectrometry. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M R Wilkins,et al.  BOLD — A biological O‐linked glycan database , 1999, Electrophoresis.

[29]  R. Aebersold,et al.  Characterization of human serum amyloid A protein isoforms separated by two‐dimensional electrophoresis by liquid chromatography/electrospray ionization tandem mass spectrometry , 1996, Electrophoresis.

[30]  M. Boguski,et al.  dbEST — database for “expressed sequence tags” , 1993, Nature Genetics.

[31]  D. Rouquié,et al.  New zwitterionic detergents improve the analysis of membrane proteins by two‐dimensional electrophoresis , 1998, Electrophoresis.

[32]  H. Schägger,et al.  Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. , 1987, Analytical biochemistry.

[33]  P. Chaurand,et al.  Peptide and protein identification by matrix-assisted laser desorption ionization (MALDI) and MALDI-post-source decay time-of-flight mass spectrometry , 1999, Journal of the American Society for Mass Spectrometry.

[34]  D. Rouquié,et al.  Towards the recovery of hydrophobic proteins on two‐dimensional electrophoresis gels , 1999, Electrophoresis.

[35]  Nicolle H. Packer,et al.  The Importance of Protein Co- and Post-Translational Modifications in Proteome Projects , 1997 .

[36]  Melanie E. Goward,et al.  The DNA sequence of human chromosome 22 , 1999, Nature.

[37]  D. Hochstrasser,et al.  Micropreparative two‐dimensional electrophoresis allowing the separation of samples containing milligram amounts of proteins , 1993, Electrophoresis.

[38]  C. Adessi,et al.  Improvement of the solubilization of proteins in two‐dimensional electrophoresis with immobilized pH gradients , 2006, Electrophoresis.

[39]  Alison Abbott,et al.  A post-genomic challenge: learning to read patterns of protein synthesis , 1999, Nature.

[40]  D. Hochstrasser,et al.  Improved and simplified in‐gel sample application using reswelling of dry immobilized pH gradients , 1997, Electrophoresis.

[41]  Marc R. Wilkins,et al.  Proteome Research: New Frontiers in Functional Genomics , 1997, Principles and Practice.

[42]  D. Hochstrasser,et al.  Extraction of membrane proteins by differential solubilization for separation using two‐dimensional gel electrophoresis , 1998, Electrophoresis.

[43]  E. Hoffman,et al.  Muscular dystrophy: identification and use of genes for diagnostics and therapeutics. , 1999, Archives of pathology & laboratory medicine.

[44]  R. Aebersold,et al.  Mass spectrometric approaches for the identification of gel‐separated proteins , 1995, Electrophoresis.

[45]  Eugen C. Buehler,et al.  Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana , 1999, Nature.

[46]  A. Gooley,et al.  Extraction of Escherichia coli proteins with organic solvents prior to two‐dimensional electrophoresis , 1999, Electrophoresis.

[47]  W. Henzel,et al.  Protein identification using 20-minute Edman cycles and sequence mixture analysis. , 1999, Analytical biochemistry.

[48]  A. Dell,et al.  Glycodelins: role in regulation of reproduction, potential for contraceptive development and diagnosis of male infertility. , 1998, Human reproduction.

[49]  S. Fields,et al.  The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[50]  R. Aebersold,et al.  Data-dependent modulation of solid-phase extraction capillary electrophoresis for the analysis of complex peptide and phosphopeptide mixtures by tandem mass spectrometry: application to endothelial nitric oxide synthase. , 1999, Analytical chemistry.

[51]  M. Mäkelä,et al.  Transfer of the enhancing effect of respiratory syncytial virus infection on subsequent allergic airway sensitization by T lymphocytes. , 1999, Journal of immunology.

[52]  J. Yates,et al.  Mining genomes: correlating tandem mass spectra of modified and unmodified peptides to sequences in nucleotide databases. , 1995, Analytical chemistry.

[53]  N G Anderson,et al.  The TYCHO system for computer analysis of two-dimensional gel electrophoresis patterns. , 1981, Clinical chemistry.

[54]  J. Zeikus,et al.  Evaluation of charge derivatization of a proteolytic protein digest for improved mass spectrometric analysis: de novo sequencing by matrix-assisted laser desorption/ionization post-source decay mass spectrometry. , 1999, Journal of mass spectrometry : JMS.

[55]  P. Cao,et al.  Phosphopeptide analysis by on-line immobilized metal-ion affinity chromatography-capillary electrophoresis-electrospray ionization mass spectrometry. , 1999, Journal of chromatography. A.

[56]  Juri Rappsilber,et al.  Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex , 1998, Nature Genetics.

[57]  A Bairoch,et al.  High-throughput mass spectrometric discovery of protein post-translational modifications. , 1999, Journal of molecular biology.

[58]  N. Anderson,et al.  An updated two‐dimensional gel database of rat liver proteins useful in gene regulation and drug effect studies , 1991 .

[59]  B. Alberts The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists , 1998, Cell.

[60]  J. Yates,et al.  Direct analysis and identification of proteins in mixtures by LC/MS/MS and database searching at the low-femtomole level. , 1997, Analytical chemistry.

[61]  R. Crystal,et al.  Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis , 1994, Nature Genetics.

[62]  N. Anderson,et al.  Proteome and proteomics: New technologies, new concepts, and new words , 1998, Electrophoresis.

[63]  G. S. Johnson,et al.  An Information-Intensive Approach to the Molecular Pharmacology of Cancer , 1997, Science.

[64]  D. Eisenberg,et al.  A combined algorithm for genome-wide prediction of protein function , 1999, Nature.

[65]  S. Fields,et al.  A novel genetic system to detect protein–protein interactions , 1989, Nature.

[66]  M. Quadroni,et al.  Proteomics and automation , 2007, Electrophoresis.

[67]  A. Görg,et al.  Steady-state two-dimensional maps of very alkaline proteins in an immobilized pH 10-12 gradient, as exemplified by histone types. , 1996, Journal of biochemical and biophysical methods.

[68]  N. Anderson,et al.  Simultaneous Measurement of Hundreds of Liver Proteins: Application in Assessment of Liver Function , 1996, Toxicologic pathology.

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

[70]  A Bairoch,et al.  A molecular scanner to automate proteomic research and to display proteome images. , 1999, Analytical chemistry.

[71]  J. van Oostrum,et al.  Mass spectrometric characterization of stathmin isoforms separated by 2D PAGE. , 1999, Journal of mass spectrometry : JMS.

[72]  A Bairoch,et al.  Protein identification with N and C-terminal sequence tags in proteome projects. , 1998, Journal of molecular biology.