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Protein Arrays in Functional Genome Research

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Bioscience Reports

Abstract

Whole-genome analyses become more and more necessary for pharmaceutical research. DNA chip hybridizations are an important tool for monitoring gene expression profiles during diseases or medical treatment. However, drug target identification and validation as well as an increasing number of antibodies and other polypeptides tested as potential drugs produce an increasing demand for genome-wide functional assays. Protein arrays are an important step into this direction. Peptide arrays and protein expression libraries are useful for the identification of antibodies and for epitope mapping. Antibody arrays allow protein quantification, protein binding studies, and protein phosphorylation assays. Tissue micro-arrays give a detailed information about the localization of macromolecules. More complex interactions can be addressed in cells spotted in array format. Finally, microfluidics chips enable us to describe the communication between cells in a tissue. In this review, possibilities, limitations and chances of different protein array techniques are discussed.

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Abbreviations

CGH:

comparative genomic hybridization

CE-IVD:

a certified product for in vitro diagnostics according to CE directive of the EU (“Communautes Européennes”)

ChIP:

chromatin immunoprecipitation

GFP:

green fluorescent protein

MEA:

microelectrode arrays

RNAi:

RNA interference

SNP:

single nucleotide polymorphism

References

  • A. Abdollahi P. Hahnfeldt C. Maercker H. J. Grone J. Debus W. Ansorge J. Folkman L. Hlatky P. E. Huber (2004) ArticleTitleEndostatin’s antiangiogenic signaling network Mol. Cell. 13 649–663 Occurrence Handle10.1016/S1097-2765(04)00102-9 Occurrence Handle15023336

    Article  PubMed  Google Scholar 

  • K. Anderson A. Potter D. Baban K. E. Davies (2003) ArticleTitleProtein expression changes in spinal muscular atrophy revealed with a novel antibody array technology Brain 126 2052–2064 Occurrence Handle10.1093/brain/awg208 Occurrence Handle12847076

    Article  PubMed  Google Scholar 

  • P. Angenendt L. Nyarsik W. Szaflarski J. Glokler K. H. Nierhaus H. Lehrach D. J. Cahill A. Lueking (2004) ArticleTitleCell-free protein expression and functional assay in nanowell chip format Anal. Chem. 76 1844–1849 Occurrence Handle10.1021/ac035114i Occurrence Handle15053642

    Article  PubMed  Google Scholar 

  • I. Bayraktaroglu O. A. Selcuk G. Dundar B. Sina E. Alpaydin (1999) ArticleTitleANNSyS: an Analog Neural Network Synthesis System Neural. Netw. 12 325–338 Occurrence Handle10.1016/S0893-6080(98)00122-1 Occurrence Handle12662707

    Article  PubMed  Google Scholar 

  • F. R. Bischoff V. Stadler F. Breitling (2002) ArticleTitleHochkomplexe Peptidarrays – Techniken, Anwendungen und Perspektiven Biospektrum 5 654–657

    Google Scholar 

  • F. R. Bischoff V. Stadler F. Breitling (2004) ArticleTitleAntikörpern auf der Spur GenomXpress 3 7–9

    Google Scholar 

  • F. Breitling F. A. Breitling T. Felgenhauer S. Fernandez K. Leibe M. Beyer V. Stadler F. R. Bischoff A. Poustka (2002) ArticleTitleHochkomplexe Peptidarrays auf Computerchips Laborwelt 3 4–6

    Google Scholar 

  • P. O. Brown D. Botstein (1999) ArticleTitleExploring the new world of the genome with DNA microarrays Nat. Genet. 21 IssueID1 Suppl 33–37 Occurrence Handle10.1038/4462 Occurrence Handle9915498

    Article  PubMed  Google Scholar 

  • D. J. Cahill E. Nordhoff (2003) ArticleTitleProtein arrays and their role in proteomics Adv. Biochem. Eng. Biotechnol. 83 177–187 Occurrence Handle12934930

    PubMed  Google Scholar 

  • A. E. Carpenter D. M. Sabatini (2004) ArticleTitleSystematic genome-wide screens of gene function Nat. Rev. Genet. 5 11–22 Occurrence Handle10.1038/nrg1248 Occurrence Handle14708012

    Article  PubMed  Google Scholar 

  • S. Cawley S. Bekiranov H. H. Ng P. Kapranov E. A. Sekinger D. Kampa A. Piccolboni V. Sementchenko J. Cheng A. J. Williams R. Wheeler B. Wong J. Drenkow M. Yamanaka S. Patel S. Brubaker H. Tammana G. Helt K. Struhl T .R. Gingeras (2004) ArticleTitleUnbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs Cell 116 499–509 Occurrence Handle10.1016/S0092-8674(04)00127-8 Occurrence Handle14980218

    Article  PubMed  Google Scholar 

  • J. Cheng E. L. Sheldon L. Wu M. J. Heller J. P. O’Connell (1998) ArticleTitleIsolation of cultured cervical carcinoma cells mixed with peripheral blood cells on a bioelectronic chip Anal. Chem. 70 2321–2326 Occurrence Handle10.1021/ac971274g Occurrence Handle9624903

    Article  PubMed  Google Scholar 

  • K. Graaf Particlede P. Hekerman O. Spelten A. Herrmann L. C. Packman K. Bussow G. Muller-Newen W. Becker (2004) ArticleTitleCharacterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and colocalization with splicing factors J. Biol. Chem. 279 4612–4624 Occurrence Handle10.1074/jbc.M310794200 Occurrence Handle14623875

    Article  PubMed  Google Scholar 

  • A. Espejo J. Cote A. Bednarek S. Richard M. T. Bedford (2002) ArticleTitleA protein-domain microarray identifies novel protein-protein interactions Biochem. J. 367 697–702 Occurrence Handle10.1042/BJ20020860 Occurrence Handle12137563

    Article  PubMed  Google Scholar 

  • R. Frank (2002) ArticleTitleHigh-density synthetic peptide microarrays: emerging tools for functional genomics and proteomics Comb. Chem. High Throughput Screen 5 429–440 Occurrence Handle12470273

    PubMed  Google Scholar 

  • P. Fromherz (2001) ArticleTitleInterfacing von Nervenzellen und Halbleiterchips Auf dem Weg zu Hirnchips und Neurocomputern? Physikalische Blätter 57 43–48

    Google Scholar 

  • H. Ge (2000) ArticleTitleUPA, a universal protein array system for quantitative detection of protein-protein, protein-DNA, protein-RNA and protein-ligand interactions Nucleic Acids Res. 28 e3 Occurrence Handle10.1093/nar/28.2.e3 Occurrence Handle10606671

    Article  PubMed  Google Scholar 

  • F. Gekeler K. Kobuch H. N. Schwahn A. Stett K. Shinoda E. Zrenner (2004) ArticleTitleSubretinal electrical stimulation of the rabbit retina with acutely implanted electrode arrays Graefes Arch. Clin. Exp. Ophthalmol. 242 587–596 Occurrence Handle10.1007/s00417-004-0862-6 Occurrence Handle15197555

    Article  PubMed  Google Scholar 

  • H. Goehler M. Lalowski U. Stelzl S. Waelter M. Stroedicke U. Worm A. Droege K. S. Lindenberg M. Knoblich C. Haenig M. Herbst J. Suopanki E. Scherzinger C. Abraham B. Bauer R. Hasenbank A. Fritzsche A. H. Ludewig K. Buessow S. H. Coleman C. A Gutekunst B. G. Landwehrmeyer H. Lehrach E. E. Wanker (2004) ArticleTitleA protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington’s disease Mol. Cell. 15 853–865 Occurrence Handle10.1016/j.molcel.2004.09.016 Occurrence Handle15383276

    Article  PubMed  Google Scholar 

  • S. P. Gygi Y. Rochon B. R. Franza R. Aebersold (1999) ArticleTitleCorrelation between protein and mRNA abundance in yeast Mol. Cell. Biol. 19 1720–1730 Occurrence Handle10022859

    PubMed  Google Scholar 

  • X. C. Jia R. Raya L. Zhang O. Foord W. L. Walker M. L. Gallo M. Haak-Frendscho L. L. Green C. G. Davis (2004) ArticleTitleA novel method of Multiplexed Competitive Antibody Binning for the characterization of monoclonal antibodies J. Immunol. Meth. 288 91–98 Occurrence Handle10.1016/j.jim.2004.02.010

    Article  Google Scholar 

  • P. Lichter S. Joos M. Bentz S. Lampel (2000) ArticleTitleComparative genomic hybridization: uses and limitations Semin. Hematol. 37 348–357 Occurrence Handle10.1053/shem.2000.16594 Occurrence Handle11071357

    Article  PubMed  Google Scholar 

  • A. Lueking A. Possling O. Huber A. Beveridge M. Horn H. Eickhoff J. Schuchardt H. Lehrach D. J. Cahill (2003) ArticleTitleA nonredundant human protein chip for antibody screening and serum profiling Mol. Cell. Proteomics 12 1342–1349 Occurrence Handle10.1074/mcp.T300001-MCP200

    Article  Google Scholar 

  • C. Maercker A. Abdollahi B. Korn P. E Huber (2003) ArticleTitleProteinexpressionsanalysen auf Antikörper Arrays: Chip-Plattform am RZPD identifiziert Hypoxiefaktoren in menschlichen Zellen GenomXpress 4 11–12

    Google Scholar 

  • J. D. Mc Pherson M. Marra L. Hillier R. H. Waterston A. Chinwalla J. Wallis M. Sekhon K. Wylie E. R. Mardis R. K. Wilson R. Fulton T. A. Kucaba C. Wagner-McPherson W. B. Barbazuk S. G. Gregory S. J. Humphray L. French R. S. Evans G. Bethel A. Whittaker J. L. Holden O. T. McCann A. Dunham C. Soderlund C. E. Scott D. R. Bentley G. Schuler H. C. Chen W. Jang E. D. Green J. R. Idol V. V. Maduro K. T. Montgomery E. Lee A. Miller S. Emerling Kucherlapati R. Gibbs S. Scherer J. H. Gorrell E. Sodergren K. Clerc-Blankenburg P. Tabor S. Naylor D. Garcia P. J. Jong Particlede J. J. Catanese N. Nowak K. Osoegawa S. Qin L. Rowen A. Madan M. Dors L. Hood B. Trask C. Friedman H. Massa V. G. Cheung I. R. Kirsch T. Reid R. Yonescu J. Weissenbach T. Bruls R. Heilig E. Branscomb A. Olsen N. Doggett J. F. Cheng T. Hawkins R. M. Myers J. Shang L. Ramirez J. Schmutz O. Velasquez K. Dixon N. E. Stone D. R. Cox D. Haussler W. J. Kent T. Furey S. Rogic S. Kennedy S. Jones A. Rosenthal G. Wen M. Schilhabel G. Gloeckner G. Nyakatura R. Siebert B. Schlegelberger J. Korenberg X. N. Chen A. Fujiyama M. Hattori A. Toyoda T. Yada H. S. Park Y. Sakaki N. Shimizu S. Asakawa K. Kawasaki T. Sasaki A. Shintani A. Shimizu K. Shibuya J. Kudoh S. Minoshima J. Ramser P. Seranski C. Hoff A. Poustka R. Reinhardt H. Lehrach InstitutionalAuthorNameInternational Human Genome Mapping Consortium (2001) ArticleTitleA physical map of the human genome Nature 409 934–941 Occurrence Handle10.1038/35057157 Occurrence Handle11237014

    Article  PubMed  Google Scholar 

  • N. Ramachandran E. Hainsworth B. Bhullar S. Eisenstein B. Rosen A. Y. Lau J. C. Walter J. LaBaer (2004) ArticleTitleSelf-assembling protein microarrays Science 305 86–90 Occurrence Handle10.1126/science.1097639 Occurrence Handle15232106

    Article  PubMed  Google Scholar 

  • W. X. Schulze M. Mann (2004) ArticleTitleA novel proteomic screen for peptide-protein interactions J. Biol. Chem. 279 10756–10764 Occurrence Handle10.1074/jbc.M309909200 Occurrence Handle14679214

    Article  PubMed  Google Scholar 

  • A. Sickmann M. Mreyen H. E. Meyer (2003) ArticleTitleMass spectrometry – a key technology in proteome research Adv. Biochem. Eng. Biotechnol. 83 141–176 Occurrence Handle12934929

    PubMed  Google Scholar 

  • R. Simon M. Mirlacher G. Sauter (2003) ArticleTitleTissue Microarrays for HT-molecular pathology Euro. Biotech. News 4 38–42

    Google Scholar 

  • J. C. Venter M. D. Adams E. W. Myers P. W. Li R. J. Mural G. G. Sutton H. O. Smith M. Yandell C. A. Evans R. A. Holt J. D. Gocayne P. Amanatides R. M. Ballew D. H. Huson J. R. Wortman Q. Zhang C. D. Kodira X. H. Zheng L. Chen M. Skupski G. Subramanian P. D. Thomas J. Zhang G. L. Gabor Miklos C. Nelson S. Broder A. G. Clark J. Nadeau V. A. McKusick N. Zinder A. J. Levine R. J. Roberts M. Simon C. Slayman M. Hunkapiller R. Bolanos A. Delcher I. Dew D. Fasulo M. Flanigan L. Florea A. Halpern S. Hannenhalli S. Kravitz S. Levy C. Mobarry K. Reinert K. Remington J. Abu-Threideh E. Beasley K. Biddick V. Bonazzi R. Brandon M. Cargill I. Chandramouliswaran R. Charlab K. Chaturvedi Z. Deng V. Di Francesco P. Dunn K. Eilbeck C. Evangelista A. E. Gabrielian W. Gan W. Ge F. Gong Z. Gu P. Guan T. J. Heiman M. E. Higgins R. R. Ji Z. Ke K. A. Ketchum Z. Lai Y. Lei Z. Li J. Li Y. Liang X. Lin F. Lu G. V. Merkulov N. Milshina H. M. Moore A. K. Naik V. A. Narayan B. Neelam D. Nusskern D. B. Rusch S. Salzberg W. Shao B. Shue J. Sun Z. Wang A. Wang X. Wang J. Wang M. Wei R. Wides C. Xiao C. Yan A. Yao J. Ye M. Zhan W. Zhang H. Zhang Q. Zhao L. Zheng F. Zhong W. Zhong S. Zhu S. Zhao D. Gilbert S. Baumhueter G. Spier C. Carter A. Cravchik T. Woodage F. Ali H. An A. Awe D. Baldwin H. Baden M. Barnstead I. Barrow K. Beeson D. Busam A. Carver A. Center M. L. Cheng L. Curry S. Danaher L. Davenport R. Desilets S. Dietz K. Dodson L. Doup S. Ferriera N. Garg A. Gluecksmann B. Hart J. Haynes C. Haynes C. Heiner S. Hladun D. Hostin J. Houck T. Howland C. Ibegwam J. Johnson F. Kalush L. Kline S. Koduru A. Love F. Mann D. May S. McCawley T. McIntosh I. McMullen M. Moy L. Moy B. Murphy K. Nelson C. Pfannkoch E. Pratts V. Puri H. Qureshi M. Reardon R. Rodriguez Y.H. Rogers D. Romblad B. Ruhfel R. Scott C. Sitter M. Smallwood E. Stewart R. Strong E. Suh R. Thomas N. N. Tint S. Tse C. Vech G. Wang J. Wetter S. Williams M. Williams S. Windsor E. Winn-Deen K. Wolfe J. Zaveri K. Zaveri J. F. Abril R. Guigo M. J. Campbell K. V. Sjolander B. Karlak A. Kejariwal H. Mi B. Lazareva T. Hatton A. Narechania K. Diemer A. Muruganujan N. Guo S. Sato V. Bafna S. Istrail R. Lippert R. Schwartz B. Walenz S. Yooseph D. Allen A. Basu J. Baxendale L. Blick M. Caminha J. Carnes-Stine P. Caulk Y. H. Chiang M. Coyne C. Dahlke A. Mays M. Dombroski M. Donnelly D. Ely S. Esparham C. Fosler H. Gire S. Glanowski K. Glasser A. Glodek M. Gorokhov K. Graham B. Gropman M. Harris J. Heil S. Henderson J. Hoover D. Jennings C. Jordan J. Jordan J. Kasha L. Kagan C. Kraft A. Levitsky M. Lewis X. Liu J. Lopez D. Ma W. Majoros J. McDaniel S. Murphy M. Newman T. Nguyen N. Nguyen M. Nodell S. Pan J. Peck M. Peterson W. Rowe R. Sanders J. Scott M. Simpson T. Smith A. Sprague T. Stockwell R. Turner E. Venter M. Wang M. Wen D. Wu M. Wu A. Xia A. Zandieh X. Zhu (2001) ArticleTitleThe sequence of the human genome Science 291 1304–1351 Occurrence Handle10.1126/science.1058040 Occurrence Handle11181995

    Article  PubMed  Google Scholar 

  • Y. Wang T. R. Wu S. Cai T. Welte Y. E. Chin (2000) ArticleTitleStat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation Mol. Cell. Biol. 20 4505–4512 Occurrence Handle10.1128/MCB.20.13.4505-4512.2000 Occurrence Handle10848577

    Article  PubMed  Google Scholar 

  • A. Wiesner R. Bogumi (2002) ArticleTitleDas ProteinChip-System in klinischer Forschung, Proteinisolierung und Proteinanalytik TranskriptLaborwelt 2002 10–13

    Google Scholar 

  • C. G. Woods E. M. Valente J. Bond E. Roberts (2004) ArticleTitleA new method for autozygosity mapping using single nucleotide polymorphisms (SNPs) and EXCLUDEAR J. Med. Genet. 41 e101–e104 Occurrence Handle10.1136/jmg.2003.016873 Occurrence Handle15286161

    Article  PubMed  Google Scholar 

  • H. Zhu M. Bilgin R. Bangham D. Hall A. Casamayor P. Bertone N. Lan R. Jansen S. Bidlingmaier T. Houfek T. Mitchell P. Miller R. A. Dean M. Gerstein M. Snyder (2001) ArticleTitleGlobal analysis of protein activities using proteome chips Science 293 2101–2105 Occurrence Handle10.1126/science.1062191 Occurrence Handle11474067

    Article  PubMed  Google Scholar 

  • J. Ziauddin D. M. Sabatini (2001) ArticleTitleMicroarrays of cells expressing defined cDNAs Nature 411 107–110 Occurrence Handle10.1038/35075114 Occurrence Handle11333987

    Article  PubMed  Google Scholar 

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Maercker, C. Protein Arrays in Functional Genome Research. Biosci Rep 25, 57–70 (2005). https://doi.org/10.1007/s10540-005-2848-y

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