Systematic antibody and antigen-based proteomic profiling with microarrays

Current approaches within affinity-based proteomics are driven both by the accessibility and availability of antigens and capture reagents, and by suitable multiplexed technologies onto which these are implemented. By combining planar microarrays and other multiparallel systems with sets of reagents, possibilities to discover new and unpredicted protein–disease associations, either via directed hypothesis-driven or via undirected hypothesis-generating target selection, can be created. In the following stages, the discoveries made during these screening phases have to be verified for potential clinical relevance based on both technical and biological aspects. The use of affinity tools throughout discovery and verification has the potential to streamline the introduction of new markers, as transition into clinically required assay formats appears straightforward. In this article, we summarize some of the current building blocks within array- and affinity-based proteomic profiling with a focus on body fluids, by giving a perspective on how current and upcoming developments in this bioscience could enable a path of pursuit for biomarker discovery.

[1]  Baogang J. Xu Combining laser capture microdissection and proteomics: Methodologies and clinical applications , 2010, Proteomics. Clinical applications.

[2]  Yongchao Ge,et al.  Development of a novel peptide microarray for large-scale epitope mapping of food allergens. , 2009, The Journal of allergy and clinical immunology.

[3]  M. Sánchez-Carbayo,et al.  Identification of Tumor-associated Autoantigens for the Diagnosis of Colorectal Cancer in Serum Using High Density Protein Microarrays* , 2009, Molecular & Cellular Proteomics.

[4]  A. Fitzpatrick,et al.  Impact of Freeze-thaw Cycles and Storage Time on Plasma Samples Used in Mass Spectrometry Based Biomarker Discovery Projects , 2005, Cancer informatics.

[5]  Marina Cretich,et al.  Protein and peptide arrays: recent trends and new directions. , 2006, Biomolecular engineering.

[6]  Dieter Stoll,et al.  Protein microarrays and multiplexed sandwich immunoassays: what beats the beads? , 2004, Combinatorial chemistry & high throughput screening.

[7]  H. Huland,et al.  Stage‐dependent increase of orosomucoid and zinc‐alpha2‐glycoprotein in urinary bladder cancer , 2005, Proteomics.

[8]  Tibor Kozár,et al.  Glycan and lectin microarrays for glycomics and medicinal applications , 2010, Medicinal research reviews.

[9]  Satoshi Nishizuka,et al.  Protein and lysate array technologies in cancer research. , 2008, Biotechnology advances.

[10]  M. Taussig,et al.  Protein microarrays: high-throughput tools for proteomics , 2009, Expert review of proteomics.

[11]  Urs Eppenberger,et al.  Protein chip based miniaturized assay for the simultaneous quantitative monitoring of cancer biomarkers in tissue extracts , 2006, Proteomics.

[12]  G. Thallinger,et al.  Novel functional profiling approach combining reverse phase protein microarrays and human 3‐D ex vivo tissue cultures: Expression of apoptosis‐related proteins in human colon cancer , 2009, Proteomics.

[13]  Y. Baba,et al.  Efficiency of cell-free protein synthesis based on a crude cell extract from Escherichia coli, wheat germ, and rabbit reticulocytes. , 2008, Journal of biotechnology.

[14]  F. Ahmed Sample preparation and fractionation for proteome analysis and cancer biomarker discovery by mass spectrometry. , 2009, Journal of separation science.

[15]  Dieter Stoll,et al.  Protein microarrays for diagnostic assays , 2009, Analytical and bioanalytical chemistry.

[16]  Debashis Ghosh,et al.  Autoantibody signatures in prostate cancer. , 2005, The New England journal of medicine.

[17]  Eshel Ben-Jacob,et al.  Organization of the autoantibody repertoire in healthy newborns and adults revealed by system level informatics of antigen microarray data , 2009, Proceedings of the National Academy of Sciences.

[18]  J. Tissot,et al.  Plasma/serum proteomics: pre-analytical issues , 2007, Expert review of proteomics.

[19]  Michael J Taussig,et al.  Printing protein arrays from DNA arrays , 2008, Nature Methods.

[20]  Mingyue He,et al.  Cell-free protein synthesis: applications in proteomics and biotechnology. , 2008, New biotechnology.

[21]  Jian-ying Zhang,et al.  Autoantibodies to tumor-associated antigens as diagnostic biomarkers in hepatocellular carcinoma and other solid tumors , 2010, Expert review of molecular diagnostics.

[22]  D. T. Wong,et al.  Human body fluid proteome analysis , 2006, Proteomics.

[23]  E. Diamandis,et al.  Strategies for discovering novel cancer biomarkers through utilization of emerging technologies , 2008, Nature Clinical Practice Oncology.

[24]  H. Sampson,et al.  Peanut epitopes for IgE and IgG4 in peanut-sensitized children in relation to severity of peanut allergy. , 2008, The Journal of allergy and clinical immunology.

[25]  Z. Namiot,et al.  MUC 1 mucin content in gastric juice of duodenal ulcer patients: effect of Helicobacter pylori eradication therapy , 2007, Clinical and Experimental Medicine.

[26]  Yoav Benjamini,et al.  Identifying differentially expressed genes using false discovery rate controlling procedures , 2003, Bioinform..

[27]  H. Dihazi,et al.  Characterization of diabetic nephropathy by urinary proteomic analysis: identification of a processed ubiquitin form as a differentially excreted protein in diabetic nephropathy patients. , 2007, Clinical chemistry.

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

[29]  Peter B. McGarvey,et al.  Protein Bioinformatics Infrastructure for the Integration and Analysis of Multiple High-Throughput “omics” Data , 2010, Adv. Bioinformatics.

[30]  I. Gipson,et al.  Assay of mucins in human tear fluid. , 2007, Experimental eye research.

[31]  Philip J R Day,et al.  Advances and perspectives in aptamer arrays. , 2009, Integrative biology : quantitative biosciences from nano to macro.

[32]  A. Pich,et al.  Mass spectrometry-based methods for biomarker detection and analysis. , 2005, Drug discovery today. Technologies.

[33]  J. Casal,et al.  Identification of cancer autoantigens in serum: toward diagnostic/prognostic testing? , 2010, Molecular Diagnosis & Therapy.

[34]  M. Borggrefe,et al.  Effect of freezing method and storage at -20 degrees C and -70 degrees C on prothrombin time, aPTT and plasma fibrinogen levels. , 2009, Thrombosis research.

[35]  M. Uhlén,et al.  Binding proteins selected from combinatorial libraries of an α-helical bacterial receptor domain , 1997, Nature Biotechnology.

[36]  Bonnie Bruce,et al.  Antigen microarray profiling of autoantibodies in rheumatoid arthritis. , 2005, Arthritis and rheumatism.

[37]  G. Perry,et al.  Antigen–antibody dissociation in Alzheimer disease: a novel approach to diagnosis , 2008, Journal of neurochemistry.

[38]  Sanjeeva Srivastava,et al.  Cell‐free synthesis‐based protein microarrays and their applications , 2010, Proteomics.

[39]  J. Hoheisel,et al.  Dual-color Proteomic Profiling of Complex Samples with a Microarray of 810 Cancer-related Antibodies* , 2010, Molecular & Cellular Proteomics.

[40]  H. Senn,et al.  Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics. , 2006, Analytical chemistry.

[41]  Carsten Grötzinger,et al.  Deciphering the Antibodyome - Peptide Arrays for Serum Antibody Biomarker Diagnostics , 2009 .

[42]  Gordon K Smyth,et al.  Statistical Applications in Genetics and Molecular Biology Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments , 2011 .

[43]  Yi Dong,et al.  Ultrasonographic feature selection and pattern classification for cervical lymph nodes using support vector machines , 2007, Comput. Methods Programs Biomed..

[44]  Mahesh Uttamchandani,et al.  Small molecule microarrays: recent advances and applications. , 2005, Current opinion in chemical biology.

[45]  Yibing Yan,et al.  Proteomic analysis of breast cancer molecular subtypes and biomarkers of response to targeted kinase inhibitors using reverse-phase protein microarrays , 2008, Molecular Cancer Therapeutics.

[46]  L. Gold,et al.  Aptamers as therapeutic and diagnostic agents. , 2000, Journal of biotechnology.

[47]  Anirban P. Mitra,et al.  Molecular markers for bladder cancer: the road to a multimarker approach , 2007, Expert review of anticancer therapy.

[48]  M. Chatterjee,et al.  Discovery of antibody biomarkers using protein microarrays of tumor antigens cloned in high throughput. , 2009, Methods in molecular biology.

[49]  Thomas O Joos,et al.  Miniaturized parallelized sandwich immunoassays. , 2008, Methods in molecular biology.

[50]  S. Hanash,et al.  Occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[51]  H. Frierson,et al.  Discovery and validation of new protein biomarkers for urothelial cancer: a prospective analysis. , 2006, The Lancet. Oncology.

[52]  J. Schwenk,et al.  Characterization of PrEST-based antibodies towards human Cytokeratin-17. , 2009, Journal of immunological methods.

[53]  A. Branscum,et al.  Accounting for response misclassification and covariate measurement error improves power and reduces bias in epidemiologic studies. , 2010, Annals of epidemiology.

[54]  R. Falk,et al.  Approaches for systematic proteome exploration. , 2007, Biomolecular engineering.

[55]  T. Peakman,et al.  Design and implementation of a high-throughput biological sample processing facility using modern manufacturing principles. , 2008, International journal of epidemiology.

[56]  John R Yates,et al.  Identifying components of protein complexes in C. elegans using co-immunoprecipitation and mass spectrometry. , 2010, Journal of proteomics.

[57]  Fay Betsou,et al.  Biobanking for better healthcare , 2008, Molecular oncology.

[58]  P. Pansri,et al.  A compact phage display human scFv library for selection of antibodies to a wide variety of antigens , 2009, BMC biotechnology.

[59]  Yan Zhang,et al.  Novel autoimmune hepatitis-specific autoantigens identified using protein microarray technology. , 2010, Journal of proteome research.

[60]  Jerzy Silberring,et al.  Biomarker discovery and clinical proteomics. , 2010, Trends in analytical chemistry : TRAC.

[61]  R. Frank,et al.  Epitope mapping of pathogenic Leptospira LipL32 , 2009, Letters in applied microbiology.

[62]  Pierre Baldi,et al.  Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[63]  T. Peterson,et al.  Membrane protein expression: no cells required. , 2009, Trends in biotechnology.

[64]  Xiaobo Yu,et al.  Protein Microarrays for Personalized Medicine , 2010, Clinical chemistry.

[65]  K. Anderson,et al.  Rapid detection of antibodies in sera using multiplexed self-assembling bead arrays. , 2009, Journal of immunological methods.

[66]  M. Uhlén,et al.  Antibodypedia, a Portal for Sharing Antibody and Antigen Validation Data*S , 2008, Molecular & Cellular Proteomics.

[67]  Fredrik Y Frejd,et al.  Affibody molecules: Engineered proteins for therapeutic, diagnostic and biotechnological applications , 2010, FEBS letters.

[68]  Sanjeeva Srivastava,et al.  Applications of protein microarrays for biomarker discovery , 2008, Proteomics. Clinical applications.

[69]  Hendrik Neubert,et al.  An immunoaffinity liquid chromatography-tandem mass spectrometry assay for the quantitation of matrix metalloproteinase 9 in mouse serum. , 2010, Analytical biochemistry.

[70]  Sophia Hober,et al.  High‐throughput protein production – Lessons from scaling up from 10 to 288 recombinant proteins per week , 2009, Biotechnology journal.

[71]  T. Joos,et al.  Microsphere-based co-immunoprecipitation in multiplex. , 2009, Analytical biochemistry.

[72]  Yanhui Hu,et al.  Next generation high density self assembling functional protein arrays , 2008, Nature Methods.

[73]  G. Auer,et al.  Proteomics in clinical prostate research , 2007, Proteomics. Clinical applications.

[74]  Kenji Usui,et al.  Protein‐Detecting Microarrays: Current Accomplishments and Requirements , 2005, Chembiochem : a European journal of chemical biology.

[75]  E. Petricoin,et al.  Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front , 2001, Oncogene.

[76]  R. Niessner,et al.  Efficient hybridoma screening technique using capture antibody based microarrays. , 2009, Analytical chemistry.

[77]  Gil Mor,et al.  Identification of differentially expressed proteins in ovarian cancer using high-density protein microarrays , 2007, Proceedings of the National Academy of Sciences.

[78]  Thomas Brinker,et al.  Multiplicity of cerebrospinal fluid functions: New challenges in health and disease , 2008, Cerebrospinal Fluid Research.

[79]  Sung‐Min Ahn,et al.  Body fluid proteomics: Prospects for biomarker discovery , 2007, Proteomics. Clinical applications.

[80]  M. Caron,et al.  Cancer Immunomics Using Autoantibody Signatures for Biomarker Discovery* , 2007, Molecular & Cellular Proteomics.

[81]  P. Nilsson,et al.  Selective IgA deficiency in early life: association to infections and allergic diseases during childhood. , 2009, Clinical immunology.

[82]  Yingchun Zhao,et al.  Quantitative proteomics and biomarker discovery in human cancer , 2009, Expert review of proteomics.

[83]  P. Riegman,et al.  Biobanking for Interdisciplinary Clinical Research , 2007, Pathobiology.

[84]  Rachel Ostroff,et al.  The stability of the circulating human proteome to variations in sample collection and handling procedures measured with an aptamer-based proteomics array. , 2010, Journal of proteomics.

[85]  M. Bradley,et al.  Functional peptide arrays for high-throughput chemical biology based applications. , 2007, Current opinion in biotechnology.

[86]  Ziding Feng,et al.  Optimized Normalization for Antibody Microarrays and Application to Serum-Protein Profiling*S , 2005, Molecular & Cellular Proteomics.

[87]  R. Lewensohn,et al.  Affinity prefractionation for MS‐based plasma proteomics , 2009, Proteomics.

[88]  Zhi-Hua Yang,et al.  Selection and affinity maturation of human antibodies against rabies virus from a scFv gene library using ribosome display. , 2009, Journal of biotechnology.

[89]  Fridtjof Lund-Johansen,et al.  Antibody Array Analysis with Label-based Detection and Resolution of Protein Size *S , 2009, Molecular & Cellular Proteomics.

[90]  K. Papp,et al.  Antigen microarrays: descriptive chemistry or functional immunomics? , 2010, Trends in immunology.

[91]  S. Lehmann,et al.  Depletion of one, six, twelve or twenty major blood proteins before proteomic analysis: the more the better? , 2009, Journal of proteomics.

[92]  Henning Hermjakob,et al.  A Reagent Resource to Identify Proteins and Peptides of Interest for the Cancer Community , 2006, Molecular & Cellular Proteomics.

[93]  N. Halama,et al.  Seromic profiling of ovarian and pancreatic cancer , 2010, Proceedings of the National Academy of Sciences.

[94]  Michael J Taussig,et al.  In situ synthesis of protein arrays. , 2008, Current opinion in biotechnology.

[95]  H. Mischak,et al.  Discovery and validation of urinary biomarkers for prostate cancer , 2008, Proteomics. Clinical applications.

[96]  Yanqing Zhang,et al.  Development of Two-Stage SVM-RFE Gene Selection Strategy for Microarray Expression Data Analysis , 2007, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[97]  Mark B Gerstein,et al.  Robust-linear-model normalization to reduce technical variability in functional protein microarrays. , 2009, Journal of proteome research.

[98]  Ulf Landegren,et al.  Sensitive Plasma Protein Analysis by Microparticle-based Proximity Ligation Assays* , 2009, Molecular & Cellular Proteomics.

[99]  I. Fodor,et al.  Statistical Analysis of Variation in the Human Plasma Proteome , 2010, Journal of biomedicine & biotechnology.

[100]  B. Luft,et al.  Profiling the humoral immune response to Borrelia burgdorferi infection with protein microarrays. , 2008, Microbial pathogenesis.

[101]  B. Haab Methods and applications of antibody microarrays in cancer research , 2003, Proteomics.

[102]  M. Baker,et al.  High‐abundance protein depletion: Comparison of methods for human plasma biomarker discovery , 2010, Electrophoresis.

[103]  Peter Filzmoser,et al.  Outlier identification in high dimensions , 2008, Comput. Stat. Data Anal..

[104]  John Spertus,et al.  Use of saliva-based nano-biochip tests for acute myocardial infarction at the point of care: a feasibility study. , 2009, Clinical chemistry.

[105]  Xuegong Zhang,et al.  Recursive SVM feature selection and sample classification for mass-spectrometry and microarray data , 2006, BMC Bioinformatics.

[106]  Axel Kowald,et al.  Profiling of Alopecia Areata Autoantigens Based on Protein Microarray Technology* , 2005, Molecular & Cellular Proteomics.

[107]  K. Kwong,et al.  Generation, affinity maturation, and characterization of a human anti-human NKG2D monoclonal antibody with dual antagonistic and agonistic activity. , 2008, Journal of molecular biology.

[108]  P. Brown,et al.  Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions , 2001, Genome Biology.

[109]  P. Felgner,et al.  Defining the humoral immune response to infectious agents using high-density protein microarrays. , 2010, Future microbiology.

[110]  Designing and implementing a large-scale automated -80 degrees C archive. , 2008, International journal of epidemiology.

[111]  Hiroko Yamada,et al.  Human protein factory for converting the transcriptome into an in vitro–expressed proteome , 2008, Nature Methods.

[112]  B. Trathnigg,et al.  Characterization of poly(ethylene glycol)-b-poly(epsilon-caprolactone) by two-dimensional liquid chromatography. , 2009, Journal of separation science.

[113]  William C Reinhold,et al.  Proteomic profiling of the NCI-60 cancer cell lines using new high-density reverse-phase lysate microarrays , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[114]  Volker Stadler,et al.  High-density peptide arrays. , 2009, Molecular bioSystems.

[115]  William Stafford Noble,et al.  How does multiple testing correction work? , 2009, Nature Biotechnology.

[116]  Kai Hilpert,et al.  Peptide arrays on cellulose support: SPOT synthesis, a time and cost efficient method for synthesis of large numbers of peptides in a parallel and addressable fashion , 2007, Nature Protocols.

[117]  S. Hanash,et al.  Challenges in deriving high-confidence protein identifications from data gathered by a HUPO plasma proteome collaborative study , 2006, Nature Biotechnology.

[118]  Andreas Plückthun,et al.  A designed ankyrin repeat protein evolved to picomolar affinity to Her2. , 2007, Journal of molecular biology.

[119]  M. Uhlén,et al.  Epitope mapping of antibodies using bacterial surface display , 2008, Nature Methods.

[120]  J. Schneider-Mergener,et al.  High-content peptide microarrays for deciphering kinase specificity and biology. , 2004, Angewandte Chemie.

[121]  M. Ruegg,et al.  Reverse protein arrays as novel approach for protein quantification in muscular dystrophies , 2010, Neuromuscular Disorders.

[122]  F. Pontén,et al.  The Human Protein Atlas—a tool for pathology , 2008, The Journal of pathology.

[123]  Gary A. Churchill,et al.  Randomization in Laboratory Procedure Is Key to Obtaining Reproducible Microarray Results , 2008, PloS one.

[124]  David H Jackson,et al.  Banking of clinical samples for proteomic biomarker studies: A consideration of logistical issues with a focus on pre‐analytical variation , 2010, Proteomics. Clinical applications.

[125]  F. Bischoff,et al.  Particle‐Based Synthesis of Peptide Arrays , 2009, Chembiochem : a European journal of chemical biology.

[126]  P. Stinissen,et al.  Autoantibody Profiling in Multiple Sclerosis Reveals Novel Antigenic Candidates1 , 2008, The Journal of Immunology.

[127]  R. Aebersold,et al.  Mass Spectrometry and Protein Analysis , 2006, Science.

[128]  Ioan Tabus,et al.  Robust estimation of protein expression ratios with lysate microarray technology , 2005, Bioinform..

[129]  S. Hanash,et al.  Mining the plasma proteome for cancer biomarkers , 2008, Nature.

[130]  Ana Fernández-Somoano,et al.  The null hypothesis significance test in health sciences research (1995-2006): statistical analysis and interpretation , 2010, BMC medical research methodology.

[131]  N. Anderson,et al.  A List of Candidate Cancer Biomarkers for Targeted Proteomics , 2006, Biomarker insights.

[132]  H. Lehrach,et al.  Recent advances of protein microarrays , 2005, Current Opinion in Chemical Biology.

[133]  Ruedi Aebersold,et al.  Targeted proteomic strategy for clinical biomarker discovery , 2009, Molecular oncology.

[134]  T. Joos,et al.  Sequential Multiplex Analyte Capturing for Phosphoprotein Profiling* , 2010, Molecular & Cellular Proteomics.

[135]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[136]  Hans Lilja,et al.  Circulating biomarkers for prostate cancer , 2007, World Journal of Urology.

[137]  R. Heinzen,et al.  Candidate Antigens for Q Fever Serodiagnosis Revealed by Immunoscreening of a Coxiella burnetii Protein Microarray , 2008, Clinical and Vaccine Immunology.

[138]  E. Slate,et al.  Overcoming the Effects of Matrix Interference in the Measurement of Urine Protein Analytes , 2012, Biomarker insights.

[139]  M. Uhlén,et al.  Antibody suspension bead arrays within serum proteomics. , 2008, Journal of proteome research.

[140]  Belinda Bullard,et al.  High throughput production of mouse monoclonal antibodies using antigen microarrays , 2005, Proteomics.

[141]  Arlo Z. Randall,et al.  Profiling humoral immune responses to P. falciparum infection with protein microarrays , 2008, Proteomics.

[142]  G. Mills,et al.  Reverse phase protein array: validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoietic stem cells , 2006, Molecular Cancer Therapeutics.

[143]  J. Kononen,et al.  Tissue microarrays for high-throughput molecular profiling of tumor specimens , 1998, Nature Medicine.

[144]  Dina Aronzon,et al.  Application of protein microarrays for multiplexed detection of antibodies to tumor antigens in breast cancer. , 2008, Journal of proteome research.

[145]  R. Ekins,et al.  Multi-analyte immunoassay. , 1989, Journal of pharmaceutical and biomedical analysis.

[146]  P. Bauer,et al.  Model Selection Based on FDR-Thresholding Optimizing the Area under the ROC-Curve , 2009, Statistical applications in genetics and molecular biology.

[147]  P. Davidsson,et al.  Comparison of different depletion strategies for improved resolution in proteomic analysis of human serum samples , 2005, Proteomics.

[148]  J. Lenormand,et al.  Production of membrane proteins using cell–free expression systems , 2007, Expert review of proteomics.

[149]  C. Borrebaeck,et al.  Antibody microarray analysis of directly labelled complex proteomes. , 2008, Current opinion in biotechnology.

[150]  M. Mann,et al.  Super-SILAC mix for quantitative proteomics of human tumor tissue , 2010, Nature Methods.

[151]  R. Longhi,et al.  Peptide microarrays for the characterization of antigenic regions of human chromogranin A , 2005, Proteomics.

[152]  R. Tibshirani,et al.  Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis , 2009, Arthritis research & therapy.

[153]  E. Lundberg,et al.  A Genecentric Human Protein Atlas for Expression Profiles Based on Antibodies* , 2008, Molecular & Cellular Proteomics.

[154]  Hans Lehrach,et al.  Profiling humoral autoimmune repertoire of dilated cardiomyopathy (DCM) patients and development of a disease‐associated protein chip , 2006, Proteomics.

[155]  H. Grönberg,et al.  Toward Next Generation Plasma Profiling via Heat-induced Epitope Retrieval and Array-based Assays* , 2010, Molecular & Cellular Proteomics.

[156]  Joakim Lundeberg,et al.  Serum Microarrays for Large Scale Screening of Protein Levels *S , 2005, Molecular & Cellular Proteomics.

[157]  David E. Gloriam,et al.  ProteomeBinders: planning a European resource of affinity reagents for analysis of the human proteome , 2007, Nature Methods.

[158]  J. Barratt,et al.  Urine proteomics: the present and future of measuring urinary protein components in disease , 2007, Canadian Medical Association Journal.

[159]  Dieter Stoll,et al.  Cell microarrays: an emerging technology for the characterization of antibodies. , 2002, BioTechniques.

[160]  W. Robinson,et al.  Antigen arrays for antibody profiling. , 2006, Current opinion in chemical biology.

[161]  Fredrik Karpe,et al.  Comparative protein profiling of serum and plasma using an antibody suspension bead array approach , 2010, Proteomics.

[162]  F. Pontén,et al.  Towards a human proteome atlas: High‐throughput generation of mono‐specific antibodies for tissue profiling , 2005, Proteomics.

[163]  S. Kingsmore Multiplexed protein measurement: technologies and applications of protein and antibody arrays , 2006, Nature Reviews Drug Discovery.

[164]  Eugene A. Kapp,et al.  Overview of the HUPO Plasma Proteome Project: Results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly‐available database , 2005, Proteomics.

[165]  Gregor Kijanka,et al.  Protein arrays as tools for serum autoantibody marker discovery in cancer. , 2009, Journal of proteomics.

[166]  T. Veenstra,et al.  The Human Plasma Proteome , 2004, Molecular & Cellular Proteomics.

[167]  M. Uhlén Mapping the human proteome using antibodies. , 2007, Molecular & cellular proteomics : MCP.

[168]  Hwee Tong Tan,et al.  Serum autoantibodies as biomarkers for early cancer detection , 2009, The FEBS journal.

[169]  D. Burton,et al.  Efficient recovery of high-affinity antibodies from a single-chain Fab yeast display library. , 2009, Journal of molecular biology.

[170]  A. Turner,et al.  Molecularly imprinted polymers for the recognition of proteins: the state of the art. , 2007, Biosensors & bioelectronics.

[171]  Yeung Sam Hung,et al.  Statistical Applications in Genetics and Molecular Biology , 2010 .

[172]  Yiling Lu,et al.  Use of Reverse Phase Protein Microarrays and Reference Standard Development for Molecular Network Analysis of Metastatic Ovarian Carcinoma* , 2005, Molecular & Cellular Proteomics.

[173]  M. A. Bopp,et al.  Zeptosens' protein microarrays: A novel high performance microarray platform for low abundance protein analysis , 2002, Proteomics.

[174]  Lello Zolla,et al.  Blood-related proteomics. , 2010, Journal of proteomics.

[175]  M. O’Connor-McCourt,et al.  Development of reverse phase protein microarrays for the validation of clusterin, a mid-abundant blood biomarker , 2009, Proteome Science.

[176]  Markus Ehrat,et al.  Antibody‐based proteomics , 2009, The FEBS journal.

[177]  B. Nelson,et al.  Protein microarrays as an application for disease biomarkers , 2009, Proteomics. Clinical applications.

[178]  Jeffrey R. Whiteaker,et al.  Head-to-head comparison of serum fractionation techniques. , 2007, Journal of proteome research.

[179]  Markus F Templin,et al.  Expanding assay dynamics: a combined competitive and direct assay system for the quantification of proteins in multiplexed immunoassays. , 2008, Clinical chemistry.

[180]  John R. Yates,et al.  The biological impact of mass-spectrometry-based proteomics , 2007, Nature.

[181]  Wei-Wei Zhang,et al.  Affinity separation and enrichment methods in proteomic analysis. , 2008, Journal of proteomics.

[182]  Dieter Stoll,et al.  Protein microarrays: catching the proteome , 2005, Mechanisms of Ageing and Development.

[183]  D. Ghosh,et al.  Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma. , 2007, Cancer research.

[184]  M. Uttamchandani,et al.  Peptide microarrays: next generation biochips for detection, diagnostics and high-throughput screening. , 2008, Current pharmaceutical design.

[185]  Doriano Fabbro,et al.  Tracing pathway activities with kinase inhibitors and reverse phase protein arrays , 2009, Proteomics. Clinical applications.

[186]  M. Uhlén,et al.  Exploring epitopes of antibodies toward the human tryptophanyl-tRNA synthetase. , 2010, New biotechnology.

[187]  David M. Rissin,et al.  Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations , 2010, Nature Biotechnology.

[188]  Benito Cañas,et al.  Mass spectrometry technologies for proteomics. , 2006, Briefings in functional genomics & proteomics.

[189]  A. Wehnert,et al.  Engineering Antibody Heavy Chain CDR3 to Create a Phage Display Fab Library Rich in Antibodies That Bind Charged Carbohydrates , 2008, The Journal of Immunology.

[190]  Dieter Stoll,et al.  Protein microarrays: Promising tools for proteomic research , 2003, Proteomics.

[191]  Mathias Uhlen,et al.  A pilot project to generate affinity reagents to human proteins , 2008, Nature Methods.

[192]  S. Kikuchi,et al.  Cystatin C in cerebrospinal fluid as a biomarker of ALS , 2009, Neuroscience Letters.

[193]  Dieter Stoll,et al.  Protein microarrays for antibody profiling: Specificity and affinity determination on a chip , 2005, Proteomics.

[194]  J. E. Chung,et al.  Construction of a large synthetic human scFv library with six diversified CDRs and high functional diversity , 2009, Molecules and cells.

[195]  R. A. van den Berg,et al.  Centering, scaling, and transformations: improving the biological information content of metabolomics data , 2006, BMC Genomics.

[196]  Ioan Tabus,et al.  Dissection of Signaling Pathways in Fourteen Breast Cancer Cell Lines Using Reverse-Phase Protein Lysate Microarray , 2006, Technology in cancer research & treatment.

[197]  Edward M. Marcotte,et al.  Human Cell Chips: Adapting DNA Microarray Spotting Technology to Cell-Based Imaging Assays , 2009, PloS one.

[198]  Stephen R Master,et al.  Quality control and protein microarrays. , 2009, Clinical chemistry.

[199]  Knut Reinert,et al.  Statistical quality assessment and outlier detection for liquid chromatography-mass spectrometry experiments , 2009, BioData Mining.

[200]  Pei Wang,et al.  The interface between biomarker discovery and clinical validation: The tar pit of the protein biomarker pipeline , 2008, Proteomics. Clinical applications.

[201]  Wei Huang,et al.  Serum proteomic signature for cystic fibrosis using an antibody microarray platform. , 2006, Molecular genetics and metabolism.

[202]  Yanhui Hu,et al.  Genome-Wide Study of Pseudomonas aeruginosa Outer Membrane Protein Immunogenicity Using Self-Assembling Protein Microarrays , 2009, Infection and Immunity.

[203]  Guillermo Izquierdo,et al.  Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of multiple sclerosis , 2008, Proceedings of the National Academy of Sciences.

[204]  Steven A Carr,et al.  Protein biomarker discovery and validation: the long and uncertain path to clinical utility , 2006, Nature Biotechnology.

[205]  Hong Wang,et al.  An optimized yeast cell-free system: sufficient for translation of human papillomavirus 58 L1 mRNA and assembly of virus-like particles. , 2008, Journal of bioscience and bioengineering.

[206]  J. Kononen,et al.  A high‐throughput strategy for protein profiling in cell microarrays using automated image analysis , 2007, Proteomics.

[207]  Harald Mischak,et al.  Urine in Clinical Proteomics* , 2008, Molecular & Cellular Proteomics.

[208]  Stephen R Master,et al.  Validation and Quality Control of Protein Microarray-based Analytical Methods , 2008, Molecular biotechnology.

[209]  N. Anderson,et al.  The Human Plasma Proteome: History, Character, and Diagnostic Prospects , 2003, Molecular & Cellular Proteomics.

[210]  Don Simone Daly,et al.  An Internal Calibration Method for Protein-Array Studies , 2010, Statistical applications in genetics and molecular biology.

[211]  N. Malla,et al.  Specific antibody detection in serum, urine and saliva samples for the diagnosis of cystic echinococcosis. , 2007, Acta tropica.

[212]  J. Lekakis,et al.  Multimarker Approach in Cardiovascular Risk Prediction , 2009, Disease markers.

[213]  Ulf Landegren,et al.  Sensitive protein detection via triple-binder proximity ligation assays , 2007, Nature Methods.

[214]  R. Hilhorst,et al.  Peptide microarrays for detailed, high-throughput substrate identification, kinetic characterization, and inhibition studies on protein kinase A. , 2009, Analytical biochemistry.

[215]  W. Kuis,et al.  Simultaneous Detection of 15 Human Cytokines in a Single Sample of Stimulated Peripheral Blood Mononuclear Cells , 2003, Clinical Diagnostic Laboratory Immunology.

[216]  M. Mehling,et al.  A modern approach to CSF analysis: Pathophysiology, clinical application, proof of concept and laboratory reporting , 2009, Clinical Neurology and Neurosurgery.

[217]  M. Taussig,et al.  Detection of protein-protein interactions by ribosome display and protein in situ immobilisation. , 2009, New biotechnology.

[218]  Shaohui Hu,et al.  Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[219]  Peter Nilsson,et al.  Validation of serum protein profiles by a dual antibody array approach. , 2009, Journal of proteomics.

[220]  Albert Duschl,et al.  specimens: systematic evaluation of labeling strategies , 2006 .

[221]  Pierre Baldi,et al.  A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray , 2010, Proceedings of the National Academy of Sciences.

[222]  N. Pearce Corporate influences on epidemiology. , 2008, International journal of epidemiology.

[223]  John Löfblom,et al.  A novel affinity protein selection system based on staphylococcal cell surface display and flow cytometry. , 2008, Protein engineering, design & selection : PEDS.

[224]  Erik K. Malm,et al.  A Human Protein Atlas for Normal and Cancer Tissues Based on Antibody Proteomics* , 2005, Molecular & Cellular Proteomics.

[225]  R J Fulton,et al.  Advanced multiplexed analysis with the FlowMetrix system. , 1997, Clinical chemistry.

[226]  Renato Tozzoli,et al.  Recent advances in diagnostic technologies and their impact in autoimmune diseases. , 2007, Autoimmunity reviews.

[227]  Gordon B Mills,et al.  Validation of reverse phase protein array for practical screening of potential biomarkers in serum and plasma: Accurate detection of CA19‐9 levels in pancreatic cancer , 2008, Proteomics.

[228]  D. Cahill,et al.  Diagnostic and prognostic biomarker discovery strategies for autoimmune disorders. , 2010, Journal of proteomics.

[229]  L. Liotta,et al.  Proteomic profiling of the cancer microenvironment by antibody arrays , 2001, Proteomics.

[230]  M. Uhlén,et al.  Discovery of epitopes for targeting the human epidermal growth factor receptor 2 (HER2) with antibodies , 2009, Molecular oncology.

[231]  Sen-Yung Hsieh,et al.  Systematical evaluation of the effects of sample collection procedures on low‐molecular‐weight serum/plasma proteome profiling , 2006, Proteomics.

[232]  Florian Gnad,et al.  Precision Mapping of an In Vivo N-Glycoproteome Reveals Rigid Topological and Sequence Constraints , 2010, Cell.

[233]  Y. Hooks,et al.  Application of phage display to high throughput antibody generation and characterization , 2007, Genome Biology.

[234]  Mathias Uhlén,et al.  Affinity as a tool in life science. , 2008, BioTechniques.

[235]  P. Nilsson,et al.  Screening for C3 Deficiency in Newborns Using Microarrays , 2009, PloS one.

[236]  Ruben H. Zamar,et al.  MDQC: a new quality assessment method for microarrays based on quality control reports , 2007, Bioinform..

[237]  A. Butte,et al.  Multiplexed protein array platforms for analysis of autoimmune diseases. , 2006, Annual review of immunology.