Proteomics and its impact upon biomedical science

Abstract Proteomics is the protein equivalent of genomics and is the study of gene expression at a functional level. The proteome of an organism is the protein complement of its genome. However, unlike the genome, the proteome is dynamic: it varies according to the cell type and the functional state of the cell. In addition, the proteome shows characteristic perturbations in response to disease and external stimuli. Proteomics combines state of the art analytical methods with bioinformatics. Here, we review the concept and technology of proteomics with specific reference to applications in medical microbiology, cellular pathology, clinical chemistry, haematology/immunology, pharmacology and toxicology.

[1]  E. Torrey,et al.  Differences in cerebrospinal fluid proteins between patients with schizophrenia and normal persons. , 1985, Clinical chemistry.

[2]  N. Anderson,et al.  Proteomics to display lovastatin‐induced protein and pathway regulation in rat liver , 2000, Electrophoresis.

[3]  E. Vretou,et al.  Mapping of Chlamydia trachomatis proteins by Immobiline‐polyacrylamide two‐dimensional electrophoresis: Spot identification by N‐terminal sequencing and immunoblotting , 1996, Electrophoresis.

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

[5]  H. Jörnvall,et al.  Identification of proteins in human prostate tumor material by two-dimensional gel electrophoresis and mass spectrometry , 2001, Cellular and Molecular Life Sciences CMLS.

[6]  J. Laplanche,et al.  CSF detection of the 14-3-3 protein in unselected patients with dementia. , 2002, Neurology.

[7]  Paul A. Haynes,et al.  Proteome Profiling—Pitfalls and Progress , 2000, Yeast.

[8]  Jiří Knížek,et al.  Protein abundance alterations in matched sets of macroscopically normal colon mucosa and colorectal carcinoma , 1999, Electrophoresis.

[9]  T. Hirano,et al.  Assessment of homogeneity in polypeptide expression in breast carcinomas shows widely variable expression in highly malignant tumors , 1996, International journal of cancer.

[10]  Steven D. Cohen,et al.  A comparative study of mouse liver proteins arylated by reactive metabolites of acetaminophen and its nonhepatotoxic regioisomer, 3'-hydroxyacetanilide. , 1995, Chemical research in toxicology.

[11]  T. Marshall,et al.  Clinical analysis of human urinary proteins using high resolution electrophoretic methods , 1998, Electrophoresis.

[12]  M. Dunn,et al.  Construction of HSC‐2DPAGE: A two‐dimensional gel electrophoresis database of heart proteins , 1997, Electrophoresis.

[13]  M. Münchbach,et al.  Quantitation and facilitated de novo sequencing of proteins by isotopic N-terminal labeling of peptides with a fragmentation-directing moiety. , 2000, Analytical chemistry.

[14]  S. Gygi,et al.  Measuring gene expression by quantitative proteome analysis. , 2000, Current opinion in biotechnology.

[15]  M. F. Lopez,et al.  Proteome analysis. I. Gene products are where the biological action is. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[16]  N G Anderson,et al.  Back to the future: The human protein index (HPI) and the agenda for post‐proteomic biology , 2001, Proteomics.

[17]  T. Marshall,et al.  Two‐Dimensional electrophoresis of human serum proteins following acute myocardial infarction , 1989, Electrophoresis.

[18]  M R Wilkins,et al.  Rapid protein identification using N-terminal "sequence tag" and amino acid analysis. , 1996, Biochemical and biophysical research communications.

[19]  M. Blaser,et al.  Two-dimensional gel electrophoresis and immunoblotting of Campylobacter pylori proteins , 1989, Infection and immunity.

[20]  D. Hochstrasser,et al.  Identification of ribosome‐associated viral and cellular basic proteins during the course of infection with herpes simplex virus type 1 , 2001, Proteomics.

[21]  R D Appel,et al.  Improving protein identification from peptide mass fingerprinting through a parameterized multi‐level scoring algorithm and an optimized peak detection , 1999, Electrophoresis.

[22]  A. Shevchenko,et al.  MALDI quadrupole time-of-flight mass spectrometry: a powerful tool for proteomic research. , 2000, Analytical chemistry.

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

[24]  M. J. Chalmers,et al.  Advances in mass spectrometry for proteome analysis. , 2000, Current opinion in biotechnology.

[25]  J R Yates,et al.  Emerging tandem-mass-spectrometry techniques for the rapid identification of proteins. , 1997, Trends in biotechnology.

[26]  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.

[27]  B. Thiede,et al.  MALDI‐MS for C‐terminal sequence determination of peptides and proteins degraded by carboxypeptidase Y and P , 1995, FEBS letters.

[28]  D. Hochstrasser,et al.  Proteomics meets cell biology: The establishment of subcellular proteomes , 2000, Electrophoresis.

[29]  S. Zolla-Pazner,et al.  Delineation of human antibody responses to culture filtrate antigens of Mycobacterium tuberculosis. , 1998, The Journal of infectious diseases.

[30]  N. Anderson,et al.  Changes in the liver protein pattern of female Wistar rats treated with the hypoglycemic agent SDZ PGU 693. , 1998, Life sciences.

[31]  C. Gerner,et al.  Similarity between nuclear matrix proteins of various cells revealed by an improved isolation method , 1998, Journal of cellular biochemistry.

[32]  Sharing of worldwide spread knowledge using hypermedia facilities & fast communication protocols (Mosaic and World Wide Web): the example of ExPASy. , 1995, Methods of information in medicine.

[33]  M. Lück,et al.  Complement activation by model drug carriers for intravenous application: determination by two-dimensional electrophoresis. , 1999, Biomaterials.

[34]  L. Huber,et al.  Subcellular fractionation, electromigration analysis and mapping of organelles. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[35]  M. Giambiagi-deMarval,et al.  Expression of heat-shock proteins in Streptococcus pyogenes and their immunoreactivity with sera from patients with streptococcal diseases. , 1998, Journal of medical microbiology.

[36]  M. Harrington,et al.  The assay development of a molecular marker for transmissible spongiform encephalopathies , 1997, Electrophoresis.

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

[38]  T. Meyer,et al.  Comparative proteome analysis of Helicobacter pylori , 2000, Molecular microbiology.

[39]  Jean-Charles Sanchez,et al.  Proteomics: new perspectives, new biomedical opportunities , 2000, The Lancet.

[40]  Gert Auer,et al.  Classification of human ovarian tumors using multivariate data analysis of polypeptide expression patterns , 2000, Nature Genetics.

[41]  O. Grenet,et al.  New insights into cyclosporine A nephrotoxicity by proteome analysis , 1998, Electrophoresis.

[42]  P. Cash,et al.  Characterisation of Haemophilus influenzae proteins by two‐dimensional gel electrophoresis , 1995, Electrophoresis.

[43]  C. Merril,et al.  Abnormal proteins in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. , 1986, The New England journal of medicine.

[44]  U. Völker,et al.  Two-dimensional gel electrophoresis: a powerful method to elucidate cellular responses to toxic compounds. , 2001, Toxicology.

[45]  M. Yacoub,et al.  The expression of heat shock protein 60 in patients with dilated cardiomyopathy. , 1999, Basic research in cardiology.

[46]  R. Johnson,et al.  Sequence analysis of peptide mixtures by automated integration of Edman and mass spectrometric data , 1992, Protein science : a publication of the Protein Society.

[47]  B. J. Hanson,et al.  A novel subfractionation approach for mitochondrial proteins: A three‐dimensional mitochondrial proteome map , 2001, Electrophoresis.

[48]  K. Fry,et al.  Identification of potential diagnostic and vaccine candidates of Helicobacter pylori by "proteome" technologies. , 1998, Helicobacter.

[49]  N. Anderson,et al.  The effects of peroxisome proliferators on protein abundances in mouse liver. , 1996, Toxicology and applied pharmacology.

[50]  D. Pappin,et al.  Peptide ladder sequencing by mass spectrometry using a novel, volatile degradation reagent. , 1994, Rapid communications in mass spectrometry : RCM.

[51]  Thomas Meitinger,et al.  MITOP, the mitochondrial proteome database: 2000 update , 2000, Nucleic Acids Res..

[52]  G. Auer,et al.  Phenotypic analysis of ovarian carcinoma: Polypeptide expression in benign, borderline and malignant tumors , 1997, International journal of cancer.

[53]  T. Ørntoft,et al.  Proteomics and immunohistochemistry define some of the steps involved in the squamous differentiation of the bladder transitional epithelium: a novel strategy for identifying metaplastic lesions. , 1999, Cancer research.

[54]  D. Figeys,et al.  Proteomics on a chip: Promising developments , 2001, Electrophoresis.

[55]  H. Jörnvall,et al.  C-Terminal Sequence Determination of Modified Peptides by MALDI MS , 1997, Journal of protein chemistry.

[56]  S. Patterson,et al.  Proteomics: the industrialization of protein chemistry. , 2000, Current opinion in biotechnology.

[57]  P. Argos,et al.  Identification of proteins in sequence databases from amino acid composition data. , 1991, Analytical biochemistry.

[58]  P. Cash Proteomics in medical microbiology , 2000, Electrophoresis.

[59]  L. Ramagli,et al.  Towards stoichiometric silver staining of proteins resolved in complex two‐dimensional electrophoresis gels: Real‐time analysis of pattern development , 1993, Electrophoresis.

[60]  P. Righetti,et al.  Isoelectric focusing in immobilized pH gradients: recent analytical and preparative developments. , 1997, Analytical biochemistry.

[61]  L. Phan-Thanh,et al.  Identification and classification of Listeria by two-dimensional protein mapping. , 1995, Research in microbiology.

[62]  L. Engstrand,et al.  Clustering of Clinical Strains ofHelicobacter pylori Analyzed by Two-Dimensional Gel Electrophoresis , 2000, Clinical Diagnostic Laboratory Immunology.

[63]  Barbara Magi,et al.  Protein expression profiles in human breast ductal carcinoma and histologically normal tissue , 1997, Electrophoresis.

[64]  Eckart Fleck,et al.  Dilated cardiomyopathy‐associated proteins and their presentation in a WWW‐accessible two‐dimensional gel protein database , 1997, Electrophoresis.

[65]  O. Gefeller,et al.  Detection of 14‐3‐3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt‐Jakob disease , 1998, Annals of neurology.

[66]  A. L. Latner,et al.  Microheterogeneity of serum myeloma immunoglobulins revealed by a technique of high resolution two‐dimensional electrophoresis , 1980 .

[67]  P. Dalbon,et al.  Differential diagnosis of prostate cancer and benign prostate hyperplasia using two‐dimensional electrophoresis , 2001, Electrophoresis.

[68]  G. L. Gabor Miklos,et al.  Integrating molecular medicine with functional proteomics: Realities and expectations , 2001, Proteomics.

[69]  D. Hochstrasser,et al.  Renal cell carcinoma and normal kidney protein expression , 1997, Electrophoresis.

[70]  C. Rohlff Proteomics in neuropsychiatric disorders. , 2001, The international journal of neuropsychopharmacology.

[71]  J. Celis,et al.  Short‐term culturing of low‐grade superficial bladder transitional cell carcinomas leads to changes in the expression levels of several proteins involved in key cellular activities , 1999, Electrophoresis.

[72]  J. Bradbury Proteomics: the next step after genomics? , 2000, The Lancet.

[73]  K. Dybvig,et al.  Protein variability among strains of Mycoplasma pulmonis , 1987, Infection and immunity.

[74]  P. Højrup,et al.  Rapid identification of proteins by peptide-mass fingerprinting , 1993, Current Biology.

[75]  R. Aebersold,et al.  Proteins of rat serum V: Adjuvant arthritis and its modulation by nonsteroidal anti‐inflammatory drugs , 2000, Electrophoresis.

[76]  T. Ørntoft,et al.  Proteome profiling of bladder squamous cell carcinomas: identification of markers that define their degree of differentiation. , 1997, Cancer research.

[77]  E. Fleck,et al.  Characterization of myocardial protein composition in dilated cardiomyopathy by two-dimensional gel electrophoresis. , 1994, European heart journal.

[78]  G. Kelloff,et al.  Effects of oltipraz and related chemoprevention compounds on gene expression in rat liver , 1995, Journal of cellular biochemistry. Supplement.

[79]  B. Chait,et al.  Protein ladder sequencing. , 1993, Science.

[80]  N. Anderson,et al.  Induction of the adipose differentiation-related protein in liver of etomoxir-treated rats. , 1996, Biochemical and biophysical research communications.

[81]  D. Lubman,et al.  Mouse liver selenium‐binding protein decreased in abundance by peroxisome proliferators , 2000, Electrophoresis.

[82]  H. Langen,et al.  Mass spectrometry: A tool for the identification of proteins separated by gels , 2000, Electrophoresis.

[83]  G. Scheele,et al.  Two-dimensional gel analysis of soluble proteins. Charaterization of guinea pig exocrine pancreatic proteins. , 1975, The Journal of biological chemistry.

[84]  F. Witzmann,et al.  Proteomic analysis of the renal effects of simulated occupational jet fuel exposure , 2000, Electrophoresis.

[85]  P. Courchesne,et al.  Two‐dimensional electrophoresis of human placental mitochondria and protein identification by mass spectrometry: Toward a human mitochondrial proteome , 1998, Electrophoresis.

[86]  A. Timperman,et al.  Proteome analysis. , 2004, Methods in molecular biology.

[87]  J. Yates,et al.  Direct analysis of protein complexes using mass spectrometry , 1999, Nature Biotechnology.

[88]  T. Meyer,et al.  Proteome analysis of the common human pathogen Helicobacter pylori , 2001, Proteomics.

[89]  K. Gevaert,et al.  Protein identification methods in proteomics , 2000, Electrophoresis.

[90]  A New Delayed Extraction MALDI-TOF MS-MS for Characterization of Protein Digests , 2000 .

[91]  A. L. Latner,et al.  High resolution electrophoresis of extracts of a baby hamster kidney cell line before and after transformation by polyoma virus , 1983 .

[92]  S. Steiner,et al.  Expression profiling in toxicology--potentials and limitations. , 2000, Toxicology letters.

[93]  D Fenyö,et al.  Identifying the proteome: software tools. , 2000, Current opinion in biotechnology.

[94]  S. Gygi,et al.  Proteome analysis: Biological assay or data archive? , 1998, Electrophoresis.

[95]  N. Wade The complete index to man. , 1981, Science.

[96]  N G Anderson,et al.  Design and implementation of a prototype Human Protein Index. , 1982, Clinical chemistry.

[97]  F. Witzmann,et al.  Proteomics: Applications and opportunities in preclinical drug development , 2000, Electrophoresis.

[98]  H. Meyer,et al.  Identification of platelet proteins separated by two‐dimensional gel electrophoresis and analyzed by matrix assisted laser desorption/ionization‐time of flight‐mass spectrometry and detection of tyrosine‐phosphorylated proteins , 2000, Electrophoresis.

[99]  H. Langen,et al.  Two‐dimensional map of basic proteins of Haemophilus influenzae , 1998, Electrophoresis.

[100]  R D Appel,et al.  Protein identification and analysis tools in the ExPASy server. , 1999, Methods in molecular biology.

[101]  L. Liotta,et al.  The role of tissue microdissection in cancer research. , 2001, Cancer journal.

[102]  P Berndt,et al.  Two‐dimensional database of mouse liver proteins: Changes in hepatic protein levels following treatment with acetaminophen or its nontoxic regioisomer 3‐acetamidophenol , 2000, Electrophoresis.

[103]  J. E. Myrick,et al.  Quantitative two-dimensional electrophoretic detection of possible urinary protein biomarkers of occupational exposure to cadmium. , 1993, Applied and theoretical electrophoresis : the official journal of the International Electrophoresis Society.

[104]  D. Pappin,et al.  The potential use of laser capture microdissection to selectively obtain distinct populations of cells for proteomic analysis — Preliminary findings , 1999, Electrophoresis.

[105]  Wayne F. Patton,et al.  A luminescent ruthenium complex for ultrasensitive detection of proteins immobilized on membrane supports. , 1999, Analytical biochemistry.

[106]  H. Kato,et al.  Expression of tropomyosin isoforms in benign and malignant human breast lesions. , 1996, British Journal of Cancer.

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

[108]  M. Yacoub,et al.  Upregulation of the Bcl-2 family of proteins in end stage heart failure. , 2000, Journal of the American College of Cardiology.

[109]  D. Russell,et al.  The interaction between Mycobacterium and the macrophage analyzed by two‐dimensional polyacrylamide gel electrophoresis , 1997, Electrophoresis.

[110]  G. Mahairas,et al.  Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis , 1996, Journal of bacteriology.

[111]  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.

[112]  J. Celis,et al.  A qualitative and quantitative protein database approach identifies individual and groups of functionally related proteins that are differentially regulated in simian virus 40 (SV40) transformed human keratinocytes: An overview of the functional changes associated with the transformed phenotype , 1994, Electrophoresis.

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

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

[115]  M J Dunn,et al.  Comparison of two‐dimensional electrophoresis patterns of heat shock protein Hsp27 species in normal and cardiomyopathic hearts , 1999, Electrophoresis.

[116]  C. Gerner,et al.  Nuclear matrix proteins specific for subtypes of human hematopoietic cells , 1999, Journal of cellular biochemistry.

[117]  F. Poirier,et al.  The BPP (protein biochemistry and proteomics) two-dimensional electrophoresis database. , 2001, Journal of chromatography. B, Biomedical sciences and applications.

[118]  G. Shaw,et al.  Rapid identification of proteins. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[119]  K. Sakaguchi,et al.  Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas , 1999, FEBS letters.

[120]  S. Patterson From electrophoretically separated protein to identification: strategies for sequence and mass analysis. , 1994, Analytical biochemistry.

[121]  J. Celis,et al.  Psoriasin (S100A7): A putative urinary marker for the follow‐up of patients with bladder squamous cell carcinomas , 1999, Electrophoresis.

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

[123]  A. Tsugita,et al.  C-terminal sequencing of protein. A novel partial acid hydrolysis and analysis by mass spectrometry. , 1992, European journal of biochemistry.

[124]  D. Harvey,et al.  Identification of protein‐bound carbohydrates by mass spectrometry , 2001, Proteomics.

[125]  P. Jenö,et al.  Internal sequences from proteins digested in polyacrylamide gels. , 1995, Analytical biochemistry.

[126]  P. J. Monardo,et al.  A distributed system for two-dimensional gel analysis , 1994, Comput. Appl. Biosci..

[127]  F. Rudert,et al.  Genomics and proteomics tools for the clinic. , 2000, Current opinion in molecular therapeutics.

[128]  K. Fry,et al.  Identification of Potential Diagnostic and Vaccine Candidates ofHelicobacter pylori by Two-Dimensional Gel Electrophoresis, Sequence Analysis, and Serum Profiling , 1998, Clinical Diagnostic Laboratory Immunology.

[129]  G. Christiansen,et al.  Electrophoretic analysis of proteins from Mycoplasma capricolum and related serotypes using extracts from intact cells and from minicells containing cloned mycoplasma DNA. , 1984, Journal of general microbiology.

[130]  G. Gonnet,et al.  Protein identification by mass profile fingerprinting. , 1993, Biochemical and biophysical research communications.

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

[132]  J. Klose,et al.  Identification of tissue proteins by amino acid analysis after purification by two-dimensional electrophoresis , 1992, Journal of protein chemistry.

[133]  A. Shevchenko,et al.  Peptide sequencing of 2-DE gel-isolated proteins by nanoelectrospray tandem mass spectrometry. , 1999, Methods in molecular biology.

[134]  B. Chait,et al.  A statistical basis for testing the significance of mass spectrometric protein identification results. , 2000, Analytical chemistry.

[135]  E. Petricoin,et al.  An approach to proteomic analysis of human tumors , 2000, Molecular carcinogenesis.

[136]  S. Pennington,et al.  Arrays for protein expression profiling: Towards a viable alternative to two‐dimensional gel electrophoresis? , 2001, Proteomics.

[137]  Morten Østergaard,et al.  Human and mouse proteomic databases: novel resources in the protein universe , 1998, FEBS letters.

[138]  P Ferrara,et al.  In-gel digestion of proteins for internal sequence analysis after one- or two-dimensional gel electrophoresis. , 1992, Analytical biochemistry.

[139]  W. Moorman,et al.  Alterations in rabbit kidney protein expression following lead exposure as analyzed by two‐dimensional gel electrophoresis , 1999, Electrophoresis.

[140]  G. Reichmann,et al.  GRA7, an excretory 29 kDa Toxoplasma gondii dense granule antigen released by infected host cells. , 1998, Molecular and biochemical parasitology.

[141]  K. Kelly,et al.  Virulence associated proteins of Brucella abortus identified by paired two-dimensional gel electrophoretic comparisons of virulent, vaccine and LPS deficient strains. , 1992, Applied and theoretical electrophoresis : the official journal of the International Electrophoresis Society.

[142]  E. Fung,et al.  Proteomic strategies for biomarker identification: progress and challenges. , 2000, Current opinion in molecular therapeutics.

[143]  Wayne F. Patton,et al.  Background‐free, high sensitivity staining of proteins in one‐ and two‐dimensional sodium dodecyl sulfate‐polyacrylamide gels using a luminescent ruthenium complex , 2000, Electrophoresis.

[144]  Wayne F. Patton,et al.  Proteome analysis. II. Protein subcellular redistribution: linking physiology to genomics via the proteome and separation technologies involved. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[145]  I. Gromova,et al.  A comprehensive protein ressource for the study of bladder cancer: http://biobase.dk/cgi‐bin/celis , 1999 .

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

[147]  B. Chait,et al.  Protein indentification using mass spectrometric information , 1998, Electrophoresis.

[148]  R. Aebersold,et al.  Proteins of rat serum: III. Gender‐related differences in protein concentration under baseline conditions and upon experimental inflammation as evaluated by two‐dimensional electrophoresis , 1999, Electrophoresis.

[149]  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.

[150]  O. Vesterberg,et al.  Plasma apolipoprotein pattern in fish-eye disease examined by high-resolution two-dimensional electrophoresis. , 1985, Clinical chemistry.

[151]  C Sander,et al.  Amino acid analysis and protein database compositional search as a rapid and inexpensive method to identify proteins. , 1994, Analytical biochemistry.

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

[153]  Katherine B. Williams,et al.  A two‐dimensional electrophoresis database of human breast epithelial cell proteins , 1997, Electrophoresis.

[154]  B. Küster,et al.  Glycosylation analysis of gel‐separated proteins , 2001, Proteomics.

[155]  I. Lefkovits,et al.  Polyoma-induced thymic epithelial tumors: analysis by 2D gel electrophoresis of tumors upon labeling the entire tumor bearing host. , 1990, Thymus.

[156]  D. Cahill,et al.  Protein and antibody arrays and their medical applications. , 2001, Journal of immunological methods.

[157]  P. O’Farrell High resolution two-dimensional electrophoresis of proteins. , 1975, The Journal of biological chemistry.

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

[159]  E. Müller,et al.  Study of Burkitt lymphoma cell line proteins by high resolution two‐dimensional gel electrophoresis and nanoelectrospray mass spectrometry , 1999, Electrophoresis.

[160]  H. Kato,et al.  Relationship between TA01 and TA02 polypeptides associated with lung adenocarcinoma and histocytological features. , 1997, British Journal of Cancer.

[161]  R L Carpenter,et al.  Toxicity of chemical mixtures:Proteomic analysis of persisting liver and kidney protein alterations induced by repeated exposure of rats to JP‐8 jet fuel vapor , 2000, Electrophoresis.

[162]  Y Wu,et al.  A fast spot segmentation algorithm for two‐dimensional gel electrophoresis analysis , 1993, Electrophoresis.

[163]  I. Miller,et al.  Proteins of rat serum IV. Time‐course of acute‐phase protein expression and its modulation by indomethacine , 1999, Electrophoresis.

[164]  S. Cordwell,et al.  Comparative proteomics of bacterial pathogens , 2001, Proteomics.

[165]  A D Olson,et al.  Elsie 4: quantitative computer analysis of sets of two-dimensional gel electrophoretograms. , 1988, Analytical biochemistry.

[166]  Wayne F. Patton,et al.  A thousand points of light: The application of fluorescence detection technologies to two‐dimensional gel electrophoresis and proteomics , 2000, Electrophoresis.

[167]  J. Ryu,et al.  High resolution two-dimensional electrophoresis: technique and potential applicability to the study of inner ear disease. , 1995, The American journal of otology.

[168]  M. Dunn,et al.  Studying heart disease using the proteomic approach. , 2000, Drug discovery today.

[169]  J. Yates,et al.  Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. , 1995, Analytical chemistry.

[170]  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.

[171]  N. Anderson,et al.  Proteomics: applications in basic and applied biology. , 2000, Current opinion in biotechnology.

[172]  U. Hellman,et al.  Improvement of an "In-Gel" digestion procedure for the micropreparation of internal protein fragments for amino acid sequencing. , 1995, Analytical biochemistry.

[173]  P. Halada,et al.  Proteomics approach in classifying the biochemical basis of the anticancer activity of the new olomoucine‐derived synthetic cyclin‐dependent kinase inhibitor, bohemine , 2000, Electrophoresis.

[174]  Jennifer M. Campbell,et al.  The characteristics of peptide collision-induced dissociation using a high-performance MALDI-TOF/TOF tandem mass spectrometer. , 2000, Analytical chemistry.

[175]  J. J. Edwards,et al.  Electrophoresis '79: Advanced Methods, Biochemical and Clinical Applications: Internal Charge Standardization for two-Dimensional electrophoresis: High-Resolution Two-Dimensional Electrophoretic Mapping of Human proteins , 1980 .

[176]  M. Wilkins,et al.  Progress with gene‐product mapping of the Mollicutes: Mycoplasma genitalium , 1995, Electrophoresis.

[177]  M. Yacoub,et al.  Cardiac protein abnormalities in dilated cardiomyopathy detected by two‐dimensional polyacrylamide gel electrophoresis , 1998, Electrophoresis.

[178]  R. Moritz,et al.  Two-dimensional mapping and microsequencing of lysosomal proteins from human placenta. , 1998, Placenta.

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

[180]  P. Cash,et al.  A proteomic analysis of erythromycin resistance in Streptococcus pneumoniae , 1999, Electrophoresis.

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

[182]  D. Hochstrasser,et al.  Colloidal carriers for intravenous drug targeting: Plasma protein adsorption patterns on surface‐modified latex particles evaluated by two‐dimensional polyacrylamide gel electrophoresis , 1993, Electrophoresis.

[183]  P. Lemkin,et al.  An efficient disk based data structure for rapid searching of quantitative two‐dimensional gel databases , 1993, Electrophoresis.

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

[185]  M. Theisen,et al.  Identification and Characterization of a 29-Kilodalton Protein from Mycobacterium tuberculosis Culture Filtrate Recognized by Mouse Memory Effector Cells , 1998, Infection and Immunity.

[186]  H. Langen,et al.  Reference map of the low molecular mass proteins of Haemophilus influenzae , 1998, Electrophoresis.

[187]  P. Matsudaira,et al.  Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. , 1987, The Journal of biological chemistry.

[188]  P. Jungblut,et al.  Toxoplasma gondii infection: analysis of serological response by 2-DE immunoblotting. , 1999, FEMS immunology and medical microbiology.

[189]  A. Burlingame,et al.  Rapid mass spectrometric peptide sequencing and mass matching for characterization of human melanoma proteins isolated by two-dimensional PAGE. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[190]  C. Rohlff Proteomics in molecular medicine: Applications in central nervous systems disorders , 2000, Electrophoresis.

[191]  C. van Broeckhoven,et al.  Molecular biological characterization of an azole-resistant Candida glabrata isolate , 1997, Antimicrobial agents and chemotherapy.

[192]  M. Goligorsky,et al.  Toward proteomics in uroscopy: urinary protein profiles after radiocontrast medium administration. , 2001, Journal of the American Society of Nephrology : JASN.

[193]  J Taylor,et al.  Quantitation of human leukocyte proteins after silver staining: A study with two‐dimensional electrophoresis , 1991, Electrophoresis.

[194]  T. Pennington,et al.  Rifampin resistance in Neisseria meningitidis due to alterations in membrane permeability , 1996, Antimicrobial agents and chemotherapy.

[195]  F. Lottspeich,et al.  Identification of mouse brain proteins after two‐dimensional electrophoresis and electroblotting by microsequence analysis and amino acid composition analysis , 1988, Electrophoresis.

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

[197]  B. Honoré,et al.  Bladder squamous cell carcinomas express psoriasin and externalize it to the urine. , 1996, The Journal of urology.

[198]  T. Toda,et al.  TMIG‐2DPAGE: A new concept of two‐dimensional gel protein database for research on aging , 1998, Electrophoresis.

[199]  X. Khawaja,et al.  Probing for drug-induced multiplex signal transduction pathways using high resolution two-dimensional gel electrophoresis: application to beta-adrenoceptor stimulation in the rat C6 glioma cell. , 1999, Brain research. Molecular brain research.

[200]  M. Mann,et al.  Proteomics to study genes and genomes , 2000, Nature.

[201]  O. Vesterberg,et al.  Two-dimensional electrophoresis of proteins in human serum: improved resolution by use of narrow pH gradients and prolonged electrophoresis. , 1984, Clinical chemistry.

[202]  P. Jungblut,et al.  Comprehensive detection of immunorelevant Borrelia garinii antigens by two‐dimensional electrophoresis , 1999, Electrophoresis.

[203]  G. Auer,et al.  Polypeptide Expression in Prostate Hyperplasia and Prostate Adenocarcinoma , 2000, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[204]  A Bairoch,et al.  Multiple parameter cross‐species protein identification using MultiIdent ‐ a world‐wide web accessible tool , 1998, Electrophoresis.

[205]  D. Hochstrasser,et al.  Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. , 1996, Biotechnology & genetic engineering reviews.

[206]  S. Patterson,et al.  Mass spectrometry and proteomics. , 2000, Physiological genomics.

[207]  P. Righetti,et al.  Isoelectric focusing in immobilized pH gradients: an update. , 1997, Journal of chromatography. B, Biomedical sciences and applications.

[208]  B E Dunn,et al.  Helicobacter pylori , 1997, Clinical microbiology reviews.

[209]  Roberto Raggiaschi,et al.  A two‐dimensional protein map of human amniotic fluid at 17 weeks' gestation , 1997, Electrophoresis.

[210]  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.

[211]  J. Ironside,et al.  Use of 14–3–3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease , 2001, Journal of neurology, neurosurgery, and psychiatry.

[212]  P. Roepstorff,et al.  Identification of proteins in polyacrylamide gels by mass spectrometric peptide mapping combined with database search. , 1994, Biological mass spectrometry.

[213]  F. Witzmann,et al.  Regional protein alterations in rat kidneys induced by lead exposure , 1999, Electrophoresis.

[214]  R. Grimm,et al.  Elevated Plasma Levels of Crosslinked Fibrinogen Gamma-chain Dimer Indicate Cancer-related Fibrin Deposition and Fibrinolysis , 2001, Thrombosis and Haemostasis.

[215]  G. Auer,et al.  Cancer proteomics: From identification of novel markers to creation of artifical learning models for tumor classification , 2000, Electrophoresis.

[216]  E. Petricoin,et al.  New technologies for biomarker analysis of prostate cancer progression: Laser capture microdissection and tissue proteomics. , 2001, Urology.

[217]  N. Anderson,et al.  Commentary: Automatic chemistry and the human protein index , 1980, The Journal of automatic chemistry.

[218]  S. H. Kaufmann,et al.  Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens , 1999, Molecular microbiology.

[219]  J. Belisle,et al.  Definition of Mycobacterium tuberculosis culture filtrate proteins by two-dimensional polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and electrospray mass spectrometry , 1997, Infection and immunity.

[220]  E. Hansen,et al.  Two-dimensional gel electrophoretic comparison of proteins from virulent and avirulent strains of Mycoplasma pneumoniae , 1979, Infection and immunity.

[221]  B. Chait,et al.  ProFound: an expert system for protein identification using mass spectrometric peptide mapping information. , 2000, Analytical chemistry.

[222]  Z. A. Trapeznikova On the Interaction of , 1959 .

[223]  O. Vesterberg,et al.  Unconcentrated human urinary proteins analysed by high resolution two‐dimensional electrophoresis with narrow pH gradients: Preliminary findings after occupational exposure to cadmium , 1985 .

[224]  R. Duncan Protein synthesis initiation factor modifications during viral infections: Implications for translational control , 1990, Electrophoresis.

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

[226]  M. Wilm,et al.  Error-tolerant identification of peptides in sequence databases by peptide sequence tags. , 1994, Analytical chemistry.

[227]  N. Anderson,et al.  Cholesterol biosynthesis regulation and protein changes in rat liver following treatment with fluvastatin. , 2001, Toxicology letters.

[228]  C. Hoogland,et al.  The establishment of a human liver nuclei two‐dimensional electrophoresis reference map , 2000, Electrophoresis.

[229]  N G Anderson,et al.  The Human Protein Index. , 1981, Clinical chemistry.

[230]  J N Weinstein,et al.  A protein expression database for the molecular pharmacology of cancer , 1997, Electrophoresis.

[231]  N. Anderson,et al.  A two-dimensional gel database of rat liver proteins useful in gene regulation and drug effects studies. , 1991, Electrophoresis.

[232]  R D Appel,et al.  A new generation of information retrieval tools for biologists: the example of the ExPASy WWW server. , 1994, Trends in biochemical sciences.

[233]  J. Celis,et al.  Bladder squamous cell carcinoma biomarkers derived from proteomics , 2000, Electrophoresis.

[234]  A comparison of liver protein changes in mice and hamsters treated with the peroxisome proliferator Wy‐14,643 , 1998, Electrophoresis.

[235]  O. Vesterberg,et al.  Effects of chemical exposure on rat serum proteins revealed by a modified technique of two‐dimensional gel electrophoresis , 1983 .

[236]  Ron D. Appel,et al.  The 1999 SWISS-2DPAGE database update , 2000, Nucleic Acids Res..

[237]  O. Vesterberg,et al.  A comparison of two‐dimensional gel electrophoresis methods for analysis of rat serum proteins following dimethylformamide exposure , 1985 .

[238]  N. Anderson,et al.  Cyclosporine A decreases the protein level of the calcium-binding protein calbindin-D 28kDa in rat kidney. , 1996, Biochemical pharmacology.

[239]  R. Raggiaschi,et al.  Acute‐phase proteins in perinatal human plasma , 1997, Electrophoresis.