Bioscience Reports

, Volume 25, Issue 1–2, pp 57–70 | Cite as

Protein Arrays in Functional Genome Research

  • Christian Maercker


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.


Protein chips antibody chips peptide arrays microfluidics functional genome analysis protein binding protein phosphorylation 



comparative genomic hybridization


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


chromatin immunoprecipitation


green fluorescent protein


microelectrode arrays


RNA interference


single nucleotide polymorphism


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abdollahi, A., Hahnfeldt, P., Maercker, C., Grone, H. J., Debus, J., Ansorge, W., Folkman, J., Hlatky, L., Huber, P. E. 2004Endostatin’s antiangiogenic signaling networkMol. Cell.13649663CrossRefPubMedGoogle Scholar
  2. Anderson, K., Potter, A., Baban, D., Davies, K. E. 2003Protein expression changes in spinal muscular atrophy revealed with a novel antibody array technologyBrain12620522064CrossRefPubMedGoogle Scholar
  3. Angenendt, P., Nyarsik, L., Szaflarski, W., Glokler, J., Nierhaus, K. H., Lehrach, H., Cahill, D. J., Lueking, A. 2004Cell-free protein expression and functional assay in nanowell chip formatAnal. Chem.7618441849CrossRefPubMedGoogle Scholar
  4. Bayraktaroglu, I., Selcuk, O. A., Dundar, G., Sina, B., Alpaydin, E. 1999ANNSyS: an Analog Neural Network Synthesis SystemNeural. Netw.12325338CrossRefPubMedGoogle Scholar
  5. Bischoff, F. R., Stadler, V., Breitling, F. 2002Hochkomplexe Peptidarrays – Techniken, Anwendungen und PerspektivenBiospektrum5654657Google Scholar
  6. Bischoff, F. R., Stadler, V., Breitling, F. 2004Antikörpern auf der SpurGenomXpress379Google Scholar
  7. Breitling, F., Breitling, F. A., Felgenhauer, T., Fernandez, S., Leibe, K., Beyer, M., Stadler, V., Bischoff, F. R., Poustka, A. 2002Hochkomplexe Peptidarrays auf ComputerchipsLaborwelt346Google Scholar
  8. Brown, P. O., Botstein, D. 1999Exploring the new world of the genome with DNA microarraysNat. Genet.213337CrossRefPubMedGoogle Scholar
  9. Cahill, D. J., Nordhoff, E. 2003Protein arrays and their role in proteomicsAdv. Biochem. Eng. Biotechnol.83177187PubMedGoogle Scholar
  10. Carpenter, A. E., Sabatini, D. M. 2004Systematic genome-wide screens of gene functionNat. Rev. Genet.51122CrossRefPubMedGoogle Scholar
  11. Cawley, S., Bekiranov, S., Ng, H. H., Kapranov, P., Sekinger, E. A., Kampa, D., Piccolboni, A., Sementchenko, V., Cheng, J., Williams, A. J., Wheeler, R., Wong, B., Drenkow, J., Yamanaka, M., Patel, S., Brubaker, S., Tammana, H., Helt, G., Struhl, K., Gingeras, T .R. 2004Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAsCell116499509CrossRefPubMedGoogle Scholar
  12. Cheng, J., Sheldon, E. L., Wu, L., Heller, M. J., O’Connell, J. P. 1998Isolation of cultured cervical carcinoma cells mixed with peripheral blood cells on a bioelectronic chipAnal. Chem.7023212326CrossRefPubMedGoogle Scholar
  13. Graaf, K., Hekerman, P., Spelten, O., Herrmann, A., Packman, L. C., Bussow, K., Muller-Newen, G., Becker, W. 2004Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and colocalization with splicing factorsJ. Biol. Chem.27946124624CrossRefPubMedGoogle Scholar
  14. Espejo, A., Cote, J., Bednarek, A., Richard, S., Bedford, M. T. 2002A protein-domain microarray identifies novel protein-protein interactionsBiochem. J.367697702CrossRefPubMedGoogle Scholar
  15. Frank, R. 2002High-density synthetic peptide microarrays: emerging tools for functional genomics and proteomicsComb. Chem. High Throughput Screen5429440PubMedGoogle Scholar
  16. Fromherz, P. 2001Interfacing von Nervenzellen und HalbleiterchipsAuf dem Weg zu Hirnchips und Neurocomputern? Physikalische Blätter574348Google Scholar
  17. Ge, H. 2000UPA, a universal protein array system for quantitative detection of protein-protein, protein-DNA, protein-RNA and protein-ligand interactionsNucleic Acids Res.28e3CrossRefPubMedGoogle Scholar
  18. Gekeler, F., Kobuch, K., Schwahn, H. N., Stett, A., Shinoda, K., Zrenner, E. 2004Subretinal electrical stimulation of the rabbit retina with acutely implanted electrode arraysGraefes Arch. Clin. Exp. Ophthalmol.242587596CrossRefPubMedGoogle Scholar
  19. Goehler, H., Lalowski, M., Stelzl, U., Waelter, S., Stroedicke, M., Worm, U., Droege, A., Lindenberg, K. S., Knoblich, M., Haenig, C., Herbst, M., Suopanki, J., Scherzinger, E., Abraham, C., Bauer, B., Hasenbank, R., Fritzsche, A., Ludewig, A. H., Buessow, K., Coleman, S. H., Gutekunst, C. A, Landwehrmeyer, B. G., Lehrach, H., Wanker, E. E. 2004A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington’s diseaseMol. Cell.15853865CrossRefPubMedGoogle Scholar
  20. Gygi, S. P., Rochon, Y., Franza, B. R., Aebersold, R. 1999Correlation between protein and mRNA abundance in yeastMol. Cell. Biol.1917201730PubMedGoogle Scholar
  21. Jia, X. C., Raya, R., Zhang, L., Foord, O., Walker, W. L., Gallo, M. L., Haak-Frendscho, M., Green, L. L., Davis, C. G. 2004A novel method of Multiplexed Competitive Antibody Binning for the characterization of monoclonal antibodiesJ. Immunol. Meth.2889198CrossRefGoogle Scholar
  22. Lichter, P., Joos, S., Bentz, M., Lampel, S. 2000Comparative genomic hybridization: uses and limitationsSemin. Hematol.37348357CrossRefPubMedGoogle Scholar
  23. Lueking, A., Possling, A., Huber, O., Beveridge, A., Horn, M., Eickhoff, H., Schuchardt, J., Lehrach, H., Cahill, D. J. 2003A nonredundant human protein chip for antibody screening and serum profilingMol. Cell. Proteomics1213421349CrossRefGoogle Scholar
  24. Maercker, C., Abdollahi, A., Korn, B., Huber, P. E 2003Proteinexpressionsanalysen auf Antikörper Arrays: Chip-Plattform am RZPD identifiziert Hypoxiefaktoren in menschlichen ZellenGenomXpress41112Google Scholar
  25. Mc Pherson, J. D. Marra, M. Hillier, L. Waterston, R. H. Chinwalla, A. Wallis, J. Sekhon, M. Wylie, K. Mardis, E. R. Wilson, R. K. Fulton, R. Kucaba, T. A. Wagner-McPherson, C. Barbazuk, W. B. Gregory, S. G. Humphray, S. J. French, L. Evans, R. S. Bethel, G. Whittaker, A. Holden, J. L. McCann, O. T. Dunham, A. Soderlund, C. Scott, C. E. Bentley, D. R. Schuler, G. Chen, H. C. Jang, W. Green, E. D. Idol, J. R. Maduro, V. V. Montgomery, K. T. Lee, E. Miller, A. Emerling, S. Kucherlapati,  Gibbs, R. Scherer, S. Gorrell, J. H. Sodergren, E. Clerc-Blankenburg, K. Tabor, P. Naylor, S. Garcia, D. Jong, P. J. Catanese, J. J. Nowak, N. Osoegawa, K. Qin, S. Rowen, L. Madan, A. Dors, M. Hood, L. Trask, B. Friedman, C. Massa, H. Cheung, V. G. Kirsch, I. R. Reid, T. Yonescu, R. Weissenbach, J. Bruls, T. Heilig, R. Branscomb, E. Olsen, A. Doggett, N. Cheng, J. F. Hawkins, T. Myers, R. M. Shang, J. Ramirez, L. Schmutz, J. Velasquez, O. Dixon, K. Stone, N. E. Cox, D. R. Haussler, D. Kent, W. J. Furey, T. Rogic, S. Kennedy, S. Jones, S. Rosenthal, A. Wen, G. Schilhabel, M. Gloeckner, G. Nyakatura, G. Siebert, R. Schlegelberger, B. Korenberg, J. Chen, X. N. Fujiyama, A. Hattori, M. Toyoda, A. Yada, T. Park, H. S. Sakaki, Y. Shimizu, N. Asakawa, S. Kawasaki, K. Sasaki, T. Shintani, A. Shimizu, A. Shibuya, K. Kudoh, J. Minoshima, S. Ramser, J. Seranski, P. Hoff, C. Poustka, A. Reinhardt, R. Lehrach, H. International Human Genome Mapping Consortium2001A physical map of the human genomeNature409934941CrossRefPubMedGoogle Scholar
  26. Ramachandran, N., Hainsworth, E., Bhullar, B., Eisenstein, S., Rosen, B., Lau, A. Y., Walter, J. C., LaBaer, J. 2004Self-assembling protein microarraysScience3058690CrossRefPubMedGoogle Scholar
  27. Schulze, W. X., Mann, M. 2004A novel proteomic screen for peptide-protein interactionsJ. Biol. Chem.2791075610764CrossRefPubMedGoogle Scholar
  28. Sickmann, A., Mreyen, M., Meyer, H. E. 2003Mass spectrometry – a key technology in proteome researchAdv. Biochem. Eng. Biotechnol.83141176PubMedGoogle Scholar
  29. Simon, R., Mirlacher, M., Sauter, G. 2003Tissue Microarrays for HT-molecular pathologyEuro. Biotech. News43842Google Scholar
  30. Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., Gocayne, J. D., Amanatides, P., Ballew, R. M., Huson, D. H., Wortman, J. R., Zhang, Q., Kodira, C. D., Zheng, X. H., Chen, L., Skupski, M., Subramanian, G., Thomas, P. D., Zhang, J., Gabor Miklos, G. L., Nelson, C., Broder, S., Clark, A. G., Nadeau, J., McKusick, V. A., Zinder, N., Levine, A. J., Roberts, R. J., Simon, M., Slayman, C., Hunkapiller, M., Bolanos, R., Delcher, A., Dew, I., Fasulo, D., Flanigan, M., Florea, L., Halpern, A., Hannenhalli, S., Kravitz, S., Levy, S., Mobarry, C., Reinert, K., Remington, K., Abu-Threideh, J., Beasley, E., Biddick, K., Bonazzi, V., Brandon, R., Cargill, M., Chandramouliswaran, I., Charlab, R., Chaturvedi, K., Deng, Z., Di Francesco, V., Dunn, P., Eilbeck, K., Evangelista, C., Gabrielian, A. E., Gan, W., Ge, W., Gong, F., Gu, Z., Guan, P., Heiman, T. J., Higgins, M. E., Ji, R. R., Ke, Z., Ketchum, K. A., Lai, Z., Lei, Y., Li, Z., Li, J., Liang, Y., Lin, X., Lu, F., Merkulov, G. V., Milshina, N., Moore, H. M., Naik, A. K., Narayan, V. A., Neelam, B., Nusskern, D., Rusch, D. B., Salzberg, S., Shao, W., Shue, B., Sun, J., Wang, Z., Wang, A., Wang, X., Wang, J., Wei, M., Wides, R., Xiao, C., Yan, C., Yao, A., Ye, J., Zhan, M., Zhang, W., Zhang, H., Zhao, Q., Zheng, L., Zhong, F., Zhong, W., Zhu, S., Zhao, S., Gilbert, D., Baumhueter, S., Spier, G., Carter, C., Cravchik, A., Woodage, T., Ali, F., An, H., Awe, A., Baldwin, D., Baden, H., Barnstead, M., Barrow, I., Beeson, K., Busam, D., Carver, A., Center, A., Cheng, M. L., Curry, L., Danaher, S., Davenport, L., Desilets, R., Dietz, S., Dodson, K., Doup, L., Ferriera, S., Garg, N., Gluecksmann, A., Hart, B., Haynes, J., Haynes, C., Heiner, C., Hladun, S., Hostin, D., Houck, J., Howland, T., Ibegwam, C., Johnson, J., Kalush, F., Kline, L., Koduru, S., Love, A., Mann, F., May, D., McCawley, S., McIntosh, T., McMullen, I., Moy, M., Moy, L., Murphy, B., Nelson, K., Pfannkoch, C., Pratts, E., Puri, V., Qureshi, H., Reardon, M., Rodriguez, R., Rogers, Y.H., Romblad, D., Ruhfel, B., Scott, R., Sitter, C., Smallwood, M., Stewart, E., Strong, R., Suh, E., Thomas, R., Tint, N. N., Tse, S., Vech, C., Wang, G., Wetter, J., Williams, S., Williams, M., Windsor, S., Winn-Deen, E., Wolfe, K., Zaveri, J., Zaveri, K., Abril, J. F., Guigo, R., Campbell, M. J., Sjolander, K. V., Karlak, B., Kejariwal, A., Mi, H., Lazareva, B., Hatton, T., Narechania, A., Diemer, K., Muruganujan, A., Guo, N., Sato, S., Bafna, V., Istrail, S., Lippert, R., Schwartz, R., Walenz, B., Yooseph, S., Allen, D., Basu, A., Baxendale, J., Blick, L., Caminha, M., Carnes-Stine, J., Caulk, P., Chiang, Y. H., Coyne, M., Dahlke, C., Mays, A., Dombroski, M., Donnelly, M., Ely, D., Esparham, S., Fosler, C., Gire, H., Glanowski, S., Glasser, K., Glodek, A., Gorokhov, M., Graham, K., Gropman, B., Harris, M., Heil, J., Henderson, S., Hoover, J., Jennings, D., Jordan, C., Jordan, J., Kasha, J., Kagan, L., Kraft, C., Levitsky, A., Lewis, M., Liu, X., Lopez, J., Ma, D., Majoros, W., McDaniel, J., Murphy, S., Newman, M., Nguyen, T., Nguyen, N., Nodell, M., Pan, S., Peck, J., Peterson, M., Rowe, W., Sanders, R., Scott, J., Simpson, M., Smith, T., Sprague, A., Stockwell, T., Turner, R., Venter, E., Wang, M., Wen, M., Wu, D., Wu, M., Xia, A., Zandieh, A., Zhu, X. 2001The sequence of the human genomeScience29113041351CrossRefPubMedGoogle Scholar
  31. Wang, Y., Wu, T. R., Cai, S., Welte, T., Chin, Y. E. 2000Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activationMol. Cell. Biol.2045054512CrossRefPubMedGoogle Scholar
  32. Wiesner, A., Bogumi, R. 2002Das ProteinChip-System in klinischer Forschung, Proteinisolierung und ProteinanalytikTranskriptLaborwelt20021013Google Scholar
  33. Woods, C. G., Valente, E. M., Bond, J., Roberts, E. 2004A new method for autozygosity mapping using single nucleotide polymorphisms (SNPs) and EXCLUDEARJ. Med. Genet.41e101e104CrossRefPubMedGoogle Scholar
  34. Zhu, H., Bilgin, M., Bangham, R., Hall, D., Casamayor, A., Bertone, P., Lan, N., Jansen, R., Bidlingmaier, S., Houfek, T., Mitchell, T., Miller, P., Dean, R. A., Gerstein, M., Snyder, M. 2001Global analysis of protein activities using proteome chipsScience29321012105CrossRefPubMedGoogle Scholar
  35. Ziauddin, J., Sabatini, D. M. 2001Microarrays of cells expressing defined cDNAsNature 411 107110CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.RZPD German Resource Center for Genome Research GmbH, Berlin-HeidelbergHeidelbergGermany

Personalised recommendations