BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Yeast as a Touchstone in Post-genomic Research: Strategies for Integrative Analysis in Functional Genomics

  • Castrillo, Juan I. (School of Biological Sciences, University of Manchester) ;
  • Oliver, Stephen G. (School of Biological Sciences, University of Manchester)
  • Published : 2004.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

The new complexity arising from the genome sequencing projects requires new comprehensive post-genomic strategies: advanced studies in regulatory mechanisms, application of new high-throughput technologies at a genome-wide scale, at the different levels of cellular complexity (genome, transcriptome, proteome and metabolome), efficient analysis of the results, and application of new bioinformatic methods in an integrative or systems biology perspective. This can be accomplished in studies with model organisms under controlled conditions. In this review a perspective of the favourable characteristics of yeast as a touchstone model in post-genomic research is presented. The state-of-the art, latest advances in the field and bottlenecks, new strategies, new regulatory mechanisms, applications (patents) and high-throughput technologies, most of them being developed and validated in yeast, are presented. The optimal characteristics of yeast as a well-defined system for comprehensive studies under controlled conditions makes it a perfect model to be used in integrative, 'systems biology' studies to get new insights into the mechanisms of regulation (regulatory networks) responsible of specific phenotypes under particular environmental conditions, to be applied to more complex organisms (e.g. plants, human).

Keywords

References

  1. Adams, A. (2003) Metabolomics: Small-molecule omics. The Scientist 17, 38-40.
  2. Adams, M. D., Celniker, S. E., Holt, R. A., Evans, C. A., Gocayne, J. D., Amanatides, P. G., Scherer, S. E., Li, P. W., Hoskins, R. A., Galle, R. F. et al. (2000) The genome sequence of Drosophila melanogaster. Science 287, 2185-2195. https://doi.org/10.1126/science.287.5461.2185
  3. Ahmad, F., Kaplan, C. D. and Stewart, E. (2002). Helicase activity is only partially required for Schizosaccharomyces pombe Rqhlp function. Yeast 19, 1381-1398.
  4. Allen, J., Davey, H M., Broadhurst, D., Heald, J. K., Rowland, J. J., Oliver, S. G. and Kell, D. B. (2003) High-throughput classification of yeast mutants using metabolic footprinting. Nat. Biotechnol. 21, 692-696. https://doi.org/10.1038/nbt823
  5. Arabidopsis Genome Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408, 796-815. https://doi.org/10.1038/35048692
  6. Bach, S., Talarek, N., Andrieu, T., Vierfond, J. M., Mettey, Y., Galons, H., Dormont, D., Meijer, L., Cullin, C. and Blondel, M. (2003) Isolation of drugs active against mammalian prions using a yeast-based screening assay. Nat. Biotechnol. 21, 1075-1081. https://doi.org/10.1038/nbt855
  7. Bader, G. D., Betel, D. and Hogue, C. W. V. (2003) BIND: the biomolecular interaction network database. Nucleic Acids Res. 31, 248-250. https://doi.org/10.1093/nar/gkg056
  8. Baganz, F., Hayes, A., Marren, D., Gardner, D. C. J. and Oliver, S. G. (1997) Suitability of replacement markers for functional analysis studies in Saccharomyces cerevisiae. Yeast 13, 1563-1573. https://doi.org/10.1002/(SICI)1097-0061(199712)13:16<1563::AID-YEA240>3.0.CO;2-6
  9. Baganz, F., Hayes, A., Farquhar, R., Butler, P. R., Gardner, D. C. J. and Oliver, S. G. (1998) Quantitative analysis of yeast gene function using competition experiments in continuous culture. Yeast 14, 1417-1427. https://doi.org/10.1002/(SICI)1097-0061(199811)14:15<1417::AID-YEA334>3.0.CO;2-N
  10. Bahls, C., Weitzrna, J. and Gallaguer, R. (2003). Model organisms. The Scientist 17, Suppl. 1.
  11. Blaxter, M. (2003) Comparative genomics: Two worms are better than one. Nature 426, 395-396. https://doi.org/10.1038/426395a
  12. Boer, V. M., de Winde, J. H., Pronk, J. T. and Piper, M. D. W. (2003). The genome-wide transcriptional responses of Saccharomyces cerevisiae grown on glucose in aerobic chemostat cultures limited for carbon, nitrogen, phosphorus, or sulfur. J. Biol. Chem. 278, 3265-3274. https://doi.org/10.1074/jbc.M209759200
  13. Bono, H., Yagi, K., Kasnkawa, T., Nikaido, I., Tominaga, N., Miki, R., Mizuno, Y., Tomaru, Y., Goto, H., Nitanda, H. et al. (2003) Systematic expression profiling of the mouse transcriptome using RIKEN cDNA microarrays. Genome Res. 13, 1318-1323. https://doi.org/10.1101/gr.1075103
  14. Boube, M., Joulia, L., Cribbs, D. L., Bourbon, H. M. (2002) Evidence for a mediator of RNA polymerase II transcriptional regulation conserved from yeast to man. cell 110, 143-151. https://doi.org/10.1016/S0092-8674(02)00830-9
  15. Brancia, F. L., Butt, A., Beynon, R. J., Hubbard, S. J., Gaskell, S. J. and Oliver, S. G. (2001) A combination of chemical derivatisation and improved bioinformatic tools optimises protein identification for proteomics. Electrophoresis 22, 552-559. https://doi.org/10.1002/1522-2683(200102)22:3<552::AID-ELPS552>3.0.CO;2-C
  16. Brazma, A, Hingamp, P., Quackenbush, J., Sherlock, G., Spellman, P., Stoeckert, C., Aach, J., Ansorge, W,. Ball, C. A., Causton, H. C., et al. (2001) Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nature Genetics 29, 365-371. https://doi.org/10.1038/ng1201-365
  17. Brown, A. J. P., Planta, R. J., Restuhadi, F., Bailey, D. A., Butler, P. R., Cadahia, J. L., Cerdan, M. E., De Jonge, M., Gardner, D. C. J., Gent, M. E. et al. (2001) Transcript analysis of 1003 novel yeast genes using high-throughput northern hybridisations. EMBO J. 20, 3177-3186. https://doi.org/10.1093/emboj/20.12.3177
  18. Bryant, C. H., Muggleton, S. H., Oliver, S. G., Kell, D. B., Reiser, P. and King, R. D. (2001) Combining active inductive programming, active learning and robotics to discover the fiunction of genes. Electron. Trans. Artif. Intell. 5, 1-36.
  19. Castrillo, J. I. and Ugalde, U. O. (1994) A general model of yeast energy metabolism in aerobic chemostat culture. Yeast 10, 185-197. https://doi.org/10.1002/yea.320100206
  20. Castrillo, J. I., Hayes, A., Mohammed, S., Gaskell, S. J. and Oliver, S. G. (2003) An optimised protocol for metabolome analysis in yeast using direct infusion electrospray mass spectrometry. Phytochemistry 62, 929-937. https://doi.org/10.1016/S0031-9422(02)00713-6
  21. Cech, T. R. (2001) The genes we share with yeast, flies, worms and mice. New clues to human health and disease. 8th Biochemical Science Report Howard Hughes Medical Institute. On-line publication (http://www.hhmi.org).
  22. Chang, F. and Peter, M. (2003) Yeasts make their mark. Nature Cell Biol. 5, 294-299. https://doi.org/10.1038/ncb0403-294
  23. Chatterjee, M. T., Khalawan, S. A. and Curran, B. P. (2001). Subtle alterations in growth medium composition can dramatically alter the percentage of unsaturated fatty acids in the yeast Saccharomyces cerevisiae. Yeast 18, 81-88. https://doi.org/10.1002/1097-0061(200101)18:1<81::AID-YEA666>3.0.CO;2-3
  24. Chen, C. N., Porubleva, L., Shearer, G., Svrakic, M., Holden, L. G., Dover, J. L., Johnston, M., Chitnis, P. R. and Kohl, D. H. (2003) Associating protein activities with their genes: rapid identification of a gene encoding a methylglyoxal reductase in the yeast Saccharomyces cerevisiae. Yeast 20, 545-554. https://doi.org/10.1002/yea.979
  25. Chervitz, S. A., Aravind, L., Sherlock, G., Ball, C. A., Koonin, E. V., Dwight, S. S., Harris, M. A., Dolinski, K., Mohr, S., Smith, T., Weng, S., Cherry, J. M. and Botstein, D. (1998) Comparison of the complete protein sets of worm and yeast: orthology and divergence. Science 282, 2022-2028. https://doi.org/10.1126/science.282.5396.2022
  26. Cho, Y. S., Kim, M. K., Cheadle, C., Neary, C., Becker, K. G. and Cho-Chung, Y. S. (2001) Antisense DNAs as multisite genomic modulators identified by DNA microarray. Proc. Natl. Acad. Sci. USA 98, 9819-9823. https://doi.org/10.1073/pnas.171314398
  27. Cho-Chung, Y. S. and Becker, K. G. (2003) A genome-wide view of antisense. Nat. Biotechnol. 21, 492.
  28. Cliften, P., Sudarsanam, P., Desikan, A., Fulton, L., Fulton, B., Majors, J., Waterston, R., Cohen, B. A. and Johnston, M. (2003) Finding fiunctional features in Saccharomyces genomes by phylogenetic footprinting. Science 301, 71-76. https://doi.org/10.1126/science.1084337
  29. Conlon, I. and Raff, M. (2003) Differences in the way a mammalian cell and yeast cells coordinate cell growth and cell-cycle progression. J. Biol, 2, 7. On-line publication (http:// jbiol.com/content/2/1/7). https://doi.org/10.1186/1475-4924-2-7
  30. Cornell, M., Paton, N. W., Hedeler, C., Kirby, F., Delneri, D., Hayes, A. and Oliver, S. G. (2003) GIMS: an integrated data storage and analysis enviromnent for genomic and functional data. Yeast 20, 1291-1306. https://doi.org/10.1002/yea.1047
  31. Costanzo, M. C., Hogan, J. D., Cusick, M. E., Davis, B. P., Fancher, A. M., Hodges, P. E., Kondu, P., Lengieza, C., LewSmith, J. E., Lingner, C., Roberg-Perez, K. J., Tillberg, M., Brooks, J. E. and Garrels, J. I. (2000) The yeast proteome database (YPD) and Caenorhabditis elegans proteome database (WormPD): comprehensive resources for the organization and comparison of model organism protein information. Nucleic Acids Res. 28, 73-76. https://doi.org/10.1093/nar/28.1.73
  32. Cutler, P. (2003) Protein arrays: the current state-of-the-art. Proteomics 3, 3-18. https://doi.org/10.1002/pmic.200390007
  33. Daniel, J. A., Torok, M. S., Sun, Z. W., Schieltz, D., Allis, C. D., Yates, J. R. and Grant, P. A. (2004) Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription. J. Biol. Chem., in press. doi:10.1074/jbc.C300494200.
  34. Daran-Lapujade, P., Jansen, M. L. A., Daran, J. M., van Gulik, W., de Winde, J. H. and Prorik, J. T. (2004) Role of transcriptional regulation in controlling fluxes in central carbon metabolism of Saccharomyces cerevisiae, a chemostat culture study. J. Biol. Chem., in press. doi:10.1074/jbc.M309578200.
  35. Delneri, D. and Oliver, S. G. (2000) Functional genomics with yeast; in The Yeast Nucleus: Frontiers in Molecular Biology, Fantes, P. A. and Beggs, J. D. (eds.), pp. 1-18, Oxford University Press. Oxford, UK.
  36. Delneri, D., Brancia, F. L. and Oliver, S. G. (2001) Towards a truly integrative biology through the functional genomics of yeast. Curr Opin. Biotechnol. 12, 87-91. https://doi.org/10.1016/S0958-1669(00)00179-8
  37. Delneri, D., Colson, I., Grammenoudi, S., Roberts, I. N., Louis, E. J. and Oliver, S. G. (2003) Engineering evolution to study speciation in yeasts. Nature 422, 68-72. https://doi.org/10.1038/nature01418
  38. Dermitzakis, E. T., Reymond, A., Scamuffa, N., Ucla, C., Kirkness, E., Rossier, C. and Antonarakis, S. E. (2003) Evolutionary discrimination of mammalian conserved non-genic sequences (CNGs) Science 302, 1033-1035. https://doi.org/10.1126/science.1087047
  39. Dillon, N. (2003) Positions, please. Nature 425, 457-458. https://doi.org/10.1038/425457a
  40. Dong, L. and Xu, C. W. (2004) Carbohydrates induce monoubiquitination of H2B in yeast. J. Biol. Chem., in press. doi 10.1074/jbc.C300505200.
  41. Doniger, S. W., Salomonis, N., Dahlquist, K. D., Vranizan, K., Lawlor, S. C. and Conklin, B. R. (2003) MAPPFinder: using gene ontology and genMAPP to create a global gene- expression profile from microarray data. Genome Biol. 4, R7. On-line publication (http://genomebiology.com/2003/4/1/R7). https://doi.org/10.1186/gb-2003-4-1-r7
  42. Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494-498. https://doi.org/10.1038/35078107
  43. European Patent Office (2003) EP Patent 1300778. Microarray data warehouse.
  44. Fafournoux, P., Bruhat, A. and Jousse, C. (2000) Amino acid regulation of gene expression. Biochem. J. 351, 1-12. https://doi.org/10.1042/0264-6021:3510001
  45. Fang, Y., Brass, A., Hoyle, D. C., Hayes, A., Bashein, A., Oliver, S. G., Waddington, D. and Rattray, M. (2003) A model-based analysis of microarray experimental error and normalisation. Nucleic Acids Res. 31, e96. https://doi.org/10.1093/nar/gng097
  46. Fernandez-Bellot, E. and Cullin, C. (2001) The protein-only theory and the yeast Saccharomyces cerevisiae; the prions and the propagons. Cell. Mol. Life Sci. 58, 1857-1878. https://doi.org/10.1007/PL00000823
  47. Ficarro, S. B., McClelancl, M. L., Stukenberg, P. T., Burke, D. J., Ross, M. M., Shabanowitz, J., Hunt, D. F. and White, F. M. (2002) Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat. Biotechnol. 20, 301-305. https://doi.org/10.1038/nbt0302-301
  48. Fiehn, O. (2001) Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks. Comp. Funct. Genomics 2, 155-168. https://doi.org/10.1002/cfg.82
  49. Fiehn, O. (2002) Metabclomics - the link between genotypes and phenotypes. Plant Mol. Biol. 48, 155-171. https://doi.org/10.1023/A:1013713905833
  50. Fiehn, O. and Weckwerth, W. (2003) Deciphering metabolic networks. Eur. J. Biochem: 270, 579-588. https://doi.org/10.1046/j.1432-1033.2003.03427.x
  51. Fiehn, O., Kopka, J., Dormann, P., Altmann, T., Trethewey, R. N. and Willmitzer, L. (2000) Metabolite profiling for plant functional genomics. Nat. Biotechnol. 18, 1157-1161. https://doi.org/10.1038/81137
  52. de la Fuente, A., Brazhnik, P. and Mendes, P. (2002a) Linking the genes: inferring quantitative gene networks from microarray data. Trends Genet. 18, 395-398. https://doi.org/10.1016/S0168-9525(02)02692-6
  53. de la Fuente, A., Snoep J. L., Westerhoff, H. V. and Mendes, P. (2002b) Metabolic control in integrated biochemical systems. Eur. J. Biochem. 269, 4399-4408. https://doi.org/10.1046/j.1432-1033.2002.03088.x
  54. Gancedo, J. M. (1998) Yeast carbon catabolite repression. Microbiol. Mol. Biol. Rev. 62, 334-361.
  55. Gasch, A. P., Spellman, P. T., Kao, C. M., Carmel-Harel, O., Eisen, M. B., Storz, O., Botstein, D. and Brown, P. O. (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell. 11, 4241-4257. https://doi.org/10.1091/mbc.11.12.4241
  56. Gavin, A. C., Bosche, M., Krause, R., Grandi, P, Marzioch, M., Bauer, A., Schultz, J., Rick, J. M., Michon, A. M., Cruciat, C. M. et al. (2002) Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415, 141-147. https://doi.org/10.1038/415141a
  57. Gavin, A. C. and Superti-Furga, G. (2003) Protein complexes and proteome organization from yeast to man. Curr. Opin. Chem. Biol. 7., 21-27. https://doi.org/10.1016/S1367-5931(02)00007-8
  58. Ghaenunaghami, S., Huh, W. K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K. and Weissman, J. S. (2003) Global analysis of protein expression in yeast. Nature 425, 737-741. https://doi.org/10.1038/nature02046
  59. Giaever, G., Chu, A. M., Ni, L., Connelly, C., Riles, L., Veronneau, S., Dow, S., Lucau-Danila, A., Anderson, K., Andre, B. et. al. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418, 387-391. https://doi.org/10.1038/nature00935
  60. Glanemann, C., Loos, A., Gorret, N., Willis, L. B., O'Brien, X. M., Lessard, P. A. and Sinskey, A. J. (2003). Disparity between changes in mRNA abundance and enzyme activity in Corynebacterium glutamicum and implications for DNA microarray analysis. Appl. Microbiol. Biotechnol. 61, 61-68. https://doi.org/10.1007/s00253-002-1191-5
  61. Goffeau, A., Barrell, B. G., Bussey, H., Davis, R. W., Dujon, B., Feldmann, H., Galibert, F, Hoheisel, J. D., Jacq, C., Johnston, M. et al. (1996) Life with 6000 genes. Science 274, 546-567. https://doi.org/10.1126/science.274.5287.546
  62. Goffeau, A., Aert, R., Agostini-Carbone, M. L., Ahmed, A., Aigle, M., Alberghina, L., Albermann, K., Albers, M., Aldea, M., Alexandraki, D., et al. (1997) The yeast genome directory. Nature 387 Suppl. 5. 5-105.
  63. Gould, K. L. and Nurse, P. (1989). Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature 342, 39-45. https://doi.org/10.1038/342039a0
  64. Griffin, J. L., Williams, H. J., Sang, E., Clarke, K., Rae, C. and Nicholson, J. K. (2001) Metabolic profiling of genetic disorders: a multitissue (1)H nuclear magnetic resonance spectroscopic and pattern recognition study into dystrophic tissue. Anal. Biochem. 293, 16-21. https://doi.org/10.1006/abio.2001.5096
  65. Grunenfelder, B. and Winzeler, E. A. (2002) Treasures and traps in genome-wide data sets: case examples from yeast. Nature Rev. Genet. 3, 653-661. https://doi.org/10.1038/nrg886
  66. Guigo, R., Dermitzakis, E. T., Agarwal, P., Ponting, C. P., Parra, G., Reymond, A., Abril, J. F, Keibler, E., Lyle, R., Ucla, C., Antonarakis, S. E. and Brent, M. R. (2003) Comparison of mouse and human genomes followed by experimental verification yields an estimated 1,019 additional genes. Proc. Natl. Acad. Sci. USA 100, 1140-1145. https://doi.org/10.1073/pnas.0337561100
  67. Gygi, S. P., Rochon, Y., Franza, B. R. and Aebersold, R. (1999) Correlation between protein and rnRNA abundance in yeast. Mol. Cell. Biol. 19, 1720-1730.
  68. Hannon, G. (2002) RNA interference. Nature 418, 244-251. https://doi.org/10.1038/418244a
  69. Hansen, J. and Johannesen, P. F. (2000) Cysteine is essential for transcriptional regulation of the sulfur assimilation genes in Saccharomyces cerevisiae. Mol. Gen. Genet. 263, 535-542. https://doi.org/10.1007/s004380051199
  70. Hartwell, L. H. and Weinert, T. A. (1989). Checkpoints: controls that ensure the order of cell cycle events. Science 246, 629-634. https://doi.org/10.1126/science.2683079
  71. Hayes, A., Zhang, N., Wu, J., Butler, P. R., Hauser, N. C., Hoheisel, J. D., Lim, F., Sharrocks, A. D. and Oliver, S. G. (2002) Hybridization array technology coupled with chemostat culture: tools to interrogate gene expression in Saccharomyces cerevisiae. Methods 26, 281-290. https://doi.org/10.1016/S1046-2023(02)00032-4
  72. Hermjakob, H., Montecchi-Palazzi, L., Bader, G., Wojcik, J., Salwinski, L., Moore, S., Orchard, S., Sarkans, U., von Mering, C., Roechert, B. et al. (2004) The HUPO PSI Molecular Interaction Format - A community standard for the representation of protein interaction data. Nature Biotechnology, in press.
  73. Ho, Y., Gruhler, A., Heilbut, A., Bader, G. D., Moore, L., Adams, S. L., Millar, A., Taylor, P., Bennett, K., Boutilier, K. et al. (2002) Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415, 180-183. https://doi.org/10.1038/415180a
  74. Howard, K. (2003) Unlocking the money-making potential of RNAi. Nat. Biotechnol. 12, 1441-1446.
  75. Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L. L., Scherer, B. and Sinclair, D. A. (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425, 191-196. https://doi.org/10.1038/nature01960
  76. Hughes, T. R., Marton, M. J., Jones, A. R., Roberts, C. J., Stoughton, R., Armour, C. D., Bennett, H. A., Coffey, E., Dai, H., He, Y. D. et al. (2000) Functional discovery via a compendium of expression profiles. Cell 102, 109-126. https://doi.org/10.1016/S0092-8674(00)00015-5
  77. Huh, W. K., Falvo, J. V., Gerke, L. C., Carroll, A. S., Howson, R. W., Weissman, J. S. and O'Shea, E. K. (2003) Global analysis of protein localization in budding yeast. Nature 425, 686-691. https://doi.org/10.1038/nature02026
  78. Ihmels, J., Levy, R. and Barkai, N. (2004) Principles of transcriptional control In the metabolic network of Saccharomyces cerevisiae. Nat. Biotechnol., In press. doi: 10.1038/nbt918.
  79. Ito, T., Chiba, T., Ozawa, R., Yoshida, M., Hattori, M. and Sakaki, Y. (2001) A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc. Natl. Acad. Sci. USA. 98, 4569-4574.
  80. Kamath, R. S., Fraser, A. G., Doug, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Le Bot, N., Moreno, S., Sohrmann, M., Welchman, D. P., Zipperlen, P. and Ahringer, J. (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421, 231-237. https://doi.org/10.1038/nature01278
  81. Kell, D. B. and King, R. D. (2000) On the optimization of classes for the assignment of unidentified reading frames in functional genomics programmes: the need for machine learning. Trends Biotechnol. 18, 93-98. https://doi.org/10.1016/S0167-7799(99)01407-9
  82. Kell, D. B. and Mendes, P. (2000) Snapshots of systems: metabolic control analysis and biotechnology in the post-genomic era; in Technological and Medical Implications of Metabolic Control Analysis, Cornish-Bowden, A. and Cardenas, M. L. (eds.), pp. 3-25, Kluwer Academic Publishers, Dordrecht, Netherlands.
  83. Kellis, M., Patterson, N., Endrizzi, M., Birren, B. and Lander, E. S. (2003) Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423, 241-254. https://doi.org/10.1038/nature01644
  84. Kitano, H. (2002) Systems biology: a brief overview. Science 295, 1662-1664. https://doi.org/10.1126/science.1069492
  85. Knight, Z. A., Schilling, B., Row, R. H., Kenski, D. M., Gibson, B. W. and Shokat, K. M. (2003) Phosphospecific proteolysis for mapping sites of protein phosphorylation. Nat. Biotechnol. 21, 1047-1054. https://doi.org/10.1038/nbt863
  86. Kodadek, T. (2001) Protein microarrays: prospects and problems. Chem. Biol. 8, 105-115. https://doi.org/10.1016/S1074-5521(00)90067-X
  87. Kryndushkin, D. S., Alexandrov, I. M., Ter-Avanesyan, M. D. and Kushnirov, V. V. (2003) Yeast [PSI+] prion aggregates are formed by small Sup35 polymers fragmented by Hsp104. J. Biol. Chem. 278, 49636-49643. https://doi.org/10.1074/jbc.M307996200
  88. Kuhn, A. N. and Kaufer, N. F. (2003) Pre-mRNA splicing in Schizosaccharomyces pombe. Regulatory role of a kinase conserved from fission yeast to mammals. Curr. Genet. 42, 241-251.
  89. Kumar, A., Harrison, P. M., Chenug, K-H., Lan, N., Echols, N., Bertone, P., Miller, P., Gerstein, M. B. and Snyder, M. (2002) An integrated approach for finding overlooked genes in yeast. Nat. Biotechnol. 20, 58-63. https://doi.org/10.1038/nbt0102-58
  90. Lal, S. P., Christopherson, R. I. and dos Remedios, C. G. (2002) Antibody arrays: an embryonic but rapidly growing technology. Drug Discov Taday 7, S143-S149. https://doi.org/10.1016/S1359-6446(02)02413-3
  91. Lane, P. G., Oliver, S. G. and Butler, P. R. (1999) Analysis of a continuous-culture technique for the selection of mutants tolerant to extreme environmental stress. Biotechnol. Bioeng. 65, 397-406. https://doi.org/10.1002/(SICI)1097-0290(19991120)65:4<397::AID-BIT4>3.0.CO;2-X
  92. Lashkari, D. A., DeRisi, J. L., McCusker, J. H., Namath, A. F., Gentile, C., Hwang, S. Y., Brown, P. O. and Davis, R. W. (1997) Yeast microarrays for genome wide parallel genetic and gene expression analysis. Proc. Natl. Acad. Sci. USA 94, 13057-13062. https://doi.org/10.1073/pnas.94.24.13057
  93. Lasko, D. R., Zamboni, N. and Sauer, U. (2000) Bacterial response to acetate challenge: a comparison of tolerance arnorng species. Appl. Microbiol. Biotechnol. 54, 243-247. https://doi.org/10.1007/s002530000339
  94. Lee, J. H., Lee, D. E., Lee, B. U. and Kim, H. S. (2003a) Global analyses of transcriptomes and proteomes of a parent strain and an L-threonine-overproducing mutant strain. J. Bacteriol. 185, 5442-5451. https://doi.org/10.1128/JB.185.18.5442-5451.2003
  95. Lee, D. Y., Yun, H., Park, S. and Lee, S. Y. (2003b) MetaFluxNet: the management of metabolic reaction information and quantitative metabolic flux analysis. Bioinformatics 19, 2144-2146. https://doi.org/10.1093/bioinformatics/btg271
  96. Levine, M. and Tjian, R. (2003) Transcriptional regulation and animal diversity. Nature 424, 147-151. https://doi.org/10.1038/nature01763
  97. Levy-Lahad, E. and Plan, S. E. (2003) A risky business. Assessing breast cancer risk. Science 302, 574-575. https://doi.org/10.1126/science.1091465
  98. Liang, P. and Pardee, A. B. (2003) Analysing differential gene expression in cancer. Nat. Rev. Cancer 3, 869-876. https://doi.org/10.1038/nrc1214
  99. Lidstrom, M. and Meldrum, D. R. (2003) Life on a chip. Nat. Rev. Microbiol. 1, 158-164. https://doi.org/10.1038/nrmicro755
  100. Lim, F. L., Hayes, A., West, A. G., Pic-Taylor, A., Morgan, B. A., Oliver, S. G. and Sharrocks, A. D. (2003) Mcmlp-induced DNA bending regulates the formation of ternary transcription factor complexes. Mol. Cell. Biol. 23, 450-461. https://doi.org/10.1128/MCB.23.2.450-461.2003
  101. Lipford, J. R. and Deshaies, R. J. (2003) Diverse roles for ubiquitin-dependent proteolysis in transcriptional activation. Nat Cell Biol. 10, 845 - 850.
  102. Mendes, P. (2002) Emerging bioinformatics for the metabolome. Brief Bioinformatics 3, 134-145. https://doi.org/10.1093/bib/3.2.134
  103. Michaud, G. A., Salcius, M., Zhou, F., Bangham, R., Bonin, J., Guo, H., Snyder, M., Predki, P. F. and Schweitzer, B. I. (2003) Analyzing antibody specificity with whole proteome microarrays. Nat. Biotechnol. 21, 1509-1512. https://doi.org/10.1038/nbt910
  104. Mitchell, P. (2002) A perspective on protein microarrays. Nat. Biotechnol. 20, 225-229. https://doi.org/10.1038/nbt0302-225
  105. Morange, M. (2002) The misunderstood gene. Harvard University Press. Cambridge, USA
  106. Mosley, A L., Lakshmanan, J., Aryal, B. K. and Ozcan, S. (2003) Glucose-mediated phosphorylation converts the transcription factor Rgtl from a repressor to an activator. J. Biol. Chem. 278, 10322-10327. https://doi.org/10.1074/jbc.M212802200
  107. Mouse Genome Sequencing Consortium (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520-562. https://doi.org/10.1038/nature01262
  108. Muller, D., Exler, S., Aguilera-Vazquez, L., Guerrero-Martin, E. and Reuss, M. (2003) Cyclic AMP mediates 1lie cell cycle dynamics of energy metabolism in Saccharomyces cerevisiae. Yeast. 20, 351-367. https://doi.org/10.1002/yea.967
  109. Muratani, M. and Tansey, W. P. (2003) How the ubiquitin-proteasome system controls transcription. Nat. Rev. Mol. Cell. Biol. 4, 192-201. https://doi.org/10.1038/nrm1049
  110. Oliver, D. J., Nikolau, B. J. and Wurtele, E. S. (2002) Functional Genomics: High-throughput mRNA, protein, and metabolite analyses. Metabolic engineering 4, 98-108. https://doi.org/10.1006/mben.2001.0212
  111. Oliver, S. G. (1996) From DNA sequence to biological function. Nature 379, 597-600. https://doi.org/10.1038/379597a0
  112. Oliver, S. G. (1997) Yeast as a navigational aid in genome analysis. Microbiology 143, 1483-1487. https://doi.org/10.1099/00221287-143-5-1483
  113. Oliver, S. G. (1998) Introduction to functional analysis of the yeast genome. Methods in Microbiology 26, 1-13. https://doi.org/10.1016/S0580-9517(08)70322-2
  114. Oliver, S. G. (2002) Functional genomics: lessons from yeast. Philos. Trans. Roy Soc. B., 357, 17-23. https://doi.org/10.1098/rstb.2001.1049
  115. Oliver, S. G., Winson, M. K., Kell, D. B. and Baganz, F. (1998) Systematic functional analysis of the yeast genome. Trends Biotechnol. 16, 373-378. https://doi.org/10.1016/S0167-7799(98)01214-1
  116. Orchard, S., Hermjakob, H. and Apweiler, R. (2003) The proteomics standards initiative. Proteomics 3, 1374-1376. https://doi.org/10.1002/pmic.200300496
  117. Outeiro, T. F. and Lindquist S. (2003) Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science 302, 1772-1775. https://doi.org/10.1126/science.1090439
  118. Ouyang, Z., Takats, Z., Blake, T. A., Gologan, B., Guymon, A. J., Wiseman, J. M., Oliver, J. C., Davisson, V. J. and Cooks, R. G. (2003) Preparing protein microarrays by soft-landing of mass-selected ions. Science 301, 1351-1354. https://doi.org/10.1126/science.1088776
  119. Payne, W. E. and Garrels, J. I. (1997). Yeast protein database (YPD): a database for the complete proteome of Saccharomyces cerevisiae. Nucleic Acids Res. 25, 57-62. (http://www.incyte.com/control/researchproducts/insilico/proteome). https://doi.org/10.1093/nar/25.1.57
  120. Pearson, H. (2003) Geneticists play the numbers game in vain. Nature 423, 576.
  121. Peri, S., Navarro, J. D., Amanchy, R., Kristiansen, T. Z., Jonnalagadda, C. K., Surendranath, V., Niranjan, V, Muthusamy, B., Gandhi, T. K., Gronborg, M. et al. (2003) Development of human protein reference database as an initial platform for approaching systems biology in humans. Genome Res. 13, 2363-2371. https://doi.org/10.1101/gr.1680803
  122. Phelps, T. J., Palumbo, A. V. and Beliaev, A. S. (2002) Metabolomics and microarrays for improved understanding of phenotypic characteristics controlled by both genomics and environmental constraints. Curr. Opin. Biotechnol. 13, 20-24. https://doi.org/10.1016/S0958-1669(02)00279-3
  123. Pratt, J. M., Petty, J., Riba-Garcia, I., Robertson, D. H. L., Gaskell, S. J., Oliver, S. G. and Beynon, R. J. (2002) Dynamics of protein turnover, a missing dimension in proteomics. Mol. Cell Proteomics 1, 579-591. https://doi.org/10.1074/mcp.M200046-MCP200
  124. Raamsdonk, L. M., Teusink, B., Broadhurst, D., Zhang, N., Hayes, A., Walsh, M. C., Berden, J. A., Brindle, K. M., Kell, D. B., Rowland, J. J., Westerhoff, H. V., van Dam, K. and Oliver, S. G. (2001) A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nat Biotechnol. 19, 45-50. https://doi.org/10.1038/83496
  125. Raponi, M. and Arndt, G. M. (2003) Double-stranded RNA-mediated gene silencing in fission yeast. Nucleic Acids Res. 31, 4481-4489. https://doi.org/10.1093/nar/gkg484
  126. Rigaut, G., Shevchenko, A., Rutz, B., Wilm, M., Mann, M. and Seraphin, B. (1999) A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol. 17, 1030-1032. https://doi.org/10.1038/13732
  127. Rohde, J. R. and Cardenas, M. E. (2003) The tor pathway regulates gene expression by linking nutrient sensing to histone acetylation. Mol. Cell. Biol. 23, 629-635. https://doi.org/10.1128/MCB.23.2.629-635.2003
  128. Rose, A. H. and Harrison, J. S. (1987-1995) The yeasts. Vol. 1-6. Academic Press, London, UK.
  129. Ross-Macdonald, P., Coelho, P. S., Roemer, T., Agarwal, S., Kumar, A., Jansen, R., Cheung, K. H., Sheehan, A., Symoniatis, D., Umansky, L. et al. (1999) Large-scale analysis of the yeast genome by transposon tagging and gene disruption. Nature 402, 413-418. https://doi.org/10.1038/46558
  130. Salzberg, S. L. (2003) Genomics: Yeast rises again. Nature 423, 233-234. https://doi.org/10.1038/423233a
  131. Sandelin, A., Hoglund, A., Lenhard, B. and Wasserman, W. W. (2003) Integrated analysis of yeast regulatory sequences for biologically linked clusters of genes. Funct. Integr. Genomics 3, 125-134. https://doi.org/10.1007/s10142-003-0086-6
  132. Schena, M., Shalon, D., Davis, R. W. and Brown, P. O. (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270, 467-470. https://doi.org/10.1126/science.270.5235.467
  133. Scherer, L. J. and Rossi, J. J. (2003) Approaches for the sequence-specific knockdown of mRNA. Nat. Biotechnol. 21, 1457-1465. https://doi.org/10.1038/nbt915
  134. Schramke, V. and Allshrie, R. (2003) Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science 301, 1069-1074. https://doi.org/10.1126/science.1086870
  135. Sherman, M. Y. and Muchowski, P. J. (2003) Making yeast tremble: yeast models as tools to study neurodegenerative disorders. Neuromolecular Med. 4, 133-146. https://doi.org/10.1385/NMM:4:1-2:133
  136. Shiio, Y. and Eisenman, R. N. (2003) Histone sumoylation is associated with transcriptional repression. Proc. Natl. Acad. Sci. USA 100, 13225-13230. https://doi.org/10.1073/pnas.1735528100
  137. Shoemaker, D. D., Sohadt, E. E., Armour, C. D., He, Y. D., Garrett-Engele, P., McDonagh, P. D., Loerch, P. M., Leonardson, A., Lum, P. Y., Cavet, G. et al. (2001) Experimental annotation of the human genome using microarray technology. Nature 409, 922-927. https://doi.org/10.1038/35057141
  138. So, E. N. and Crowe, D. L. (2000) Characterization of a retinoic acid responsive element in the human ets-l promoter. IUBMB Lift 50, 365-370. https://doi.org/10.1080/713803742
  139. Spellinan, P. T., Sherlock, G., Zhang, M. Q., Iyer, V. R., Anders, K., Eisen, M. B., Brown, P.O., Botstein, D. and Futcher, B. (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol. Biol. Cell 9, 3273-3297. https://doi.org/10.1091/mbc.9.12.3273
  140. Spruill, S., Hardy, S., Weir, B. S., and Lu, J. (2002) Assessing sources of variability in microarray gene expression data. BioTechniques 33, 916-923.
  141. Tate, J. J. and Cooper, T. G. (2003) Tor1/2 regulation of retrograde gene expression in Saccharomyces cerevisiae derives indirectly as a consequence of alterations in ammonia metabolism. J. Biol. Chem. 278, 36924-36933. https://doi.org/10.1074/jbc.M301829200
  142. Taylor, C. F., Paton, N. W., Garwood, K. L., Kirby, P. D., Stead, D. A., Yin, Z., Deutsch, E. W., Selway, L., Walker, J., Riha-Garcia, I. et al. (2003) A systematic approach to modelling capturing and disseminating proteomics experimental data. Nat. Biotechnol. 21, 247-254. https://doi.org/10.1038/nbt0303-247
  143. ter Kuile, B. H. (1999) Regulation and adaptation of glucose metabolism of the parasitic protist Leishmania donovani at the enzyme and mRNA levels. J. Bacteriol. 181, 4863-4872.
  144. ter Kuile, B. H. and Westerhoff, H. V. (2001) Transcriptome meets metabolome: hierarchical and metabolic regulation of the glycolytic pathway. FEBS Lett. 500, 169-171. https://doi.org/10.1016/S0014-5793(01)02613-8
  145. ter Linde, J. J., Liang, H., Davis, R. W., Steensma, H. Y., van Dijken, J. P and Prorik, J. T (1999) Genome-wide transcriptional analysis of aerobic and anaerobic chemostat cultures of Saccharomyces cerevisiae. J. Bacteriol. 181, 7409-7413.
  146. Teusink, B., Baganz, F., Westerhoff, H. V. and Oliver, S. G. (1998) Metabolic control analysis as a tool in the elucidation of the function of novel genes. Methods Microbiol. 26, 297-336. https://doi.org/10.1016/S0580-9517(08)70338-6
  147. The Caenorhabditis elegans Sequencing Consortium (1998) Genome sequence of the nematode C. elegans: A platform for investigating biology. Science 282, 2012-2018. https://doi.org/10.1126/science.282.5396.2012
  148. The FANTOM Consortium and the RIKEN Genome Exploration Research Group Phase I & II Tearu (2002) Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420, 563-573. https://doi.org/10.1038/nature01266
  149. The International Human Genome Mapping Consortium (2001a) Initial sequencing and analysis of the human genome. Nature 409, 860-921. https://doi.org/10.1038/35057062
  150. The International Human Genome Mapping Consortium (2001b) A physical map of the human genome. Nature 409, 934-941. https://doi.org/10.1038/35057157
  151. The International Human Genome Mapping Consortium (2003) Completion of the Hmnan Genome Project. (Press release 14th April 2003) (http://www.genome.gov/11006929; http://www.sanger.ac.uk/Info/Press/2003/030414. shtml).
  152. Tilstone, C. (2003) Vital statistics. Nature 424, 610-613. https://doi.org/10.1038/424610a
  153. Trethewey, R. N. (2001) Gene discovery via metabolic profiling. Curr. Opin. Biotechnol. 12, 135-138. https://doi.org/10.1016/S0958-1669(00)00187-7
  154. Trethewey, R. N., Krotzky, A. J. and Willmitzer, L. (1999) Metabolic profiling: a Rosetta stone for genomics? Curr. Opin. Plant Biol. 2, 83-85. https://doi.org/10.1016/S1369-5266(99)80017-X
  155. Uetz, P., Giot, L., Cagney, G., Mansfield, T. A, Judson, R. S., Knight, J. R, Lockshon, D, Narayan, V, Srinivasan, M., Pochart, P. et al. (2000) A comprehensive analysis of proteinprotein interactions in Saccharomyces cerevisiae. Nature 403, 623-627. https://doi.org/10.1038/35001009
  156. Urbanczyk-Wochniak, E., Luedemann, A, Kopka, J., Selbig, J., Roessner-Tunali, U., WIlmitzer, L. and Fernie, A. R. (2003) Parallel analysis of transcript and metabolic profiles: a new approach in systems biology. EMBO Rep. 4, 989-993. https://doi.org/10.1038/sj.embor.embor944
  157. US Patent Office (2003) US Patent 6544742. Detection of genes regulated by EGF in breast cancer.
  158. US Patent Office (2003) US Patent 2003124581. Newborn screening for hemoglobinopathy by DNA microarray analysis.
  159. US Patent Office (2003) US Patent 2003170672. Quality control method of DNA microarray.
  160. US Patent Office (2003) US Patent 2003180774. Exploiting genomes in the search for new drugs.
  161. US Patent Office (2003) US Patent 2003180800. Stable isotope based dynamic metabolic profiling of living organisms for characterization of metabolic diseases, drug testing and drug development.
  162. Verger, A., Perdomo, J. and Crossley, M. (2003) Modification With SUMO. A role in transcriptional regulation. EMBO Rep. 4, 137-142. https://doi.org/10.1038/sj.embor.embor738
  163. Volpe, T., Schramke, V., Hamilton, G. L., White, S. A., Tang, G., Martienssen, R. A. and Allshire, R. C. (2003) RNA interference is required for normal centromere function in fission yeast. Chromosome Res. 11, 137-146. https://doi.org/10.1023/A:1022815931524
  164. von Mering, C., Krause, R., Snel, B., Cornell, M., Oliver, S. G., Fields, S. and Bark, P. (2002) Comparative assessment of largescale data sets of proteinprotein interactions. Nature 417, 399-403.
  165. Walker, G. M. (1999) Synchronization of yeast cell populations. Methads Cell Sci. 21, 87-93. https://doi.org/10.1023/A:1009824520278
  166. Warringer, J. and Blomberg, A. (2003) Automated screening in enviromnental arrays allows analysis of quantitative phenotypic profiles in Saccharomyces cerevisiae. Yeast 20, 53-67. https://doi.org/10.1002/yea.931
  167. Washburn, M. P. (2003) Soft landing for protein chips. Nat. Biotechnol. 21, 1156-1157. https://doi.org/10.1038/nbt1003-1156
  168. Watkins, S. M. and German, J. B. (2002) Metabolomics and biochemical profiling in drug discovery and development. Curr. Opin. Mol. Ther 4, 224-228.
  169. Weckwerth, W. (2003) Metabolomics in systems biology. Annu. Rev. Plant. Biol. 54, 669-689. https://doi.org/10.1146/annurev.arplant.54.031902.135014
  170. Weckwerth, W. and Fiehn, O. (2002) Can we discover novel pathways using metabolomic analysis? Curr. Opin. Biotechnol. 13, 156-160. https://doi.org/10.1016/S0958-1669(02)00299-9
  171. Weusthuis, R. A., Pronk, J. T., van den Broek, P. J. and van Dijken, J. P. (1994) Chemostat cultivation as a tool for studies on sugar transport in yeasts. Microbiol. Rev. 58, 616-630.
  172. Willingham, S., Outeiro, T. F., DeVit M. J., Lindquist, S. L. and Muchowski, P. J. (2003) Yeast genes that enhance the toxicity of a mutant huntingtin fragment or $\alpha$-synuclein. Science 302, 1769-1772. https://doi.org/10.1126/science.1090389
  173. Winzeler, E. A., Shoemaker, D. D., Astromoff A., Liang, H., Anderson, K., Andre, B., Bangham, R., Benito, R., Boeke, J. D., Bussey, H. et al. (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901-906. https://doi.org/10.1126/science.285.5429.901
  174. Wodicka, L., Dong, H., Mittmann, M., Ho, M. H. and Lockhart, D. J. (1997) Genome-wide expression monitoring in Saccharomyces cerevisiae. Nature Biotechnol. 15, 1359-1367. https://doi.org/10.1038/nbt1297-1359
  175. Wohlschlegel, J. A. and Yates, J. R. (2003) Proteomics: Wheres Waldo in yeast? Nat. 425, 671-672. https://doi.org/10.1038/425671a
  176. Wood, V., Gwilliam, R., Rajandream, M. A., Lyne, M., Lyne, R., Stewart, A., Sgouros, J., Peat, N., Hayles, J., Baker, S. et al. (2002) The genome sequence of Schizosaccharomyces pombe. Nature 415, 871-880. https://doi.org/10.1038/nature724
  177. World Intellectual Property Organisation (1999) WO Patent 9957306. Method for diagnosing a vascular condition.
  178. World Intellectual Property Organisation (2001) WO Patent 0140896. System and method for metabolic profiling.
  179. World Intellectual Property Organisation (2001) WO Patent 0178652. Methods for drug discovery, disease treatment and diagnosis using metabolomics.
  180. World Intellectual Property Organisation (2001) WO Patent 0194946. Microarrays for performing proteomic analyses.
  181. World Intellectual Property Organisation (2002) WO Patent 02057989. Metabolome profiling methods using chromatographic and spectroscopic data in pattern recognition analysis.
  182. World Intellectual Property Organisation (2002) WO Patent 02092118. Global analysis of protein activities using proteome chips.
  183. World Intellectual Property Organisation (2002) WO Patent 0218646. Gene discovery using microarrays.
  184. World Intellectual Property Organisation (2002) WO Patent 0239120. Method for identifying the proteome of cells using an antibody library microarray.
  185. World Intellectual Property Organisation (2003) WO Patent 03025213. Yeast proteome analysis.
  186. World Intellectual Property Organisation (2003) WO Patent 03058238. Combined metabolomic, proteomic and transcriptomic analysis from one, single sample and suitable statistical evaluation data.
  187. World Intellectual Property Organisation (2003) WO Patent 03070918. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid.
  188. World Intellectual Property Organisation (2003) WO Patent 03087371. Antiviral therapy on the basis of RNA interference.
  189. Wu, L. F., Hughes, T. R., Davierwala, A. P., Robinson, M. D., Stoughton, R. and Altschuler S. J. (2002) Large-scale prediction of Saccharomyces cerevisiae gene function using overlapping transcriptional clusters. Nat. Genet. 31, 255-265. https://doi.org/10.1038/ng906
  190. Yamada, K., Lim, J., Dale, J. M., Chen, H., Shinn, P., Palm, C. J., Southwick, A. M., Wu, H. C., Kim, C, Nguyen, M. et al. (2003) Empirical analysis of transcriptional activity in the Arabidopsis genome. Science 302, 842-846. https://doi.org/10.1126/science.1088305
  191. Yao, T. (2002) Bioinformatics for the genomic sciences and towards systems biology. Japanese activities in the post-genome era. Prog. Biophys. Mol. Biol. 80, 23-42. https://doi.org/10.1016/S0079-6107(02)00011-1
  192. Zeng, Q., Morales, A. J., and Cottarel, G. (2001) Fungi and humans: closer than you think. Trends Genet. 17, 682-684. https://doi.org/10.1016/S0168-9525(01)02498-2
  193. Zhang, N., Osborn, M., Gitsham, P., Yen, K., Miller, J. R. and Oliver, S. G. (2003) Using yeast to place human genes in functional categories. Gene 303, 121-129. https://doi.org/10.1016/S0378-1119(02)01142-3
  194. Zhu, H. and Snyder, M. (2003) Protein chip technology. Curr. Opin. Chem. Biol. 7, 55-63. https://doi.org/10.1016/S1367-5931(02)00005-4
  195. Zhu, H., Bilgin, M. and Snyder, M. (2003) Proteomics. Annu. Rev. Biochem: 72, 783-812. https://doi.org/10.1146/annurev.biochem.72.121801.161511
  196. Zhu, H., Bilgin, M., Bangham, R., Hall, D., Casarnayor, A, Bertone, P., Lan, N., Jansen, R., Bidlingmaier, S., Houfek, T., Mitchell, T., Miller, P., Dean, R. A., Gerstein, M. and Snyder, M. (2001) Global analysis of protein activities using proteome chips. Science 293, 2101-2105. https://doi.org/10.1126/science.1062191

Cited by

  1. Proteomics: Applications Relevant to Transfusion Medicine vol.20, pp.1, 2006, https://doi.org/10.1016/j.tmrv.2005.08.006
  2. Metabolic footprinting and systems biology: the medium is the message vol.3, pp.7, 2005, https://doi.org/10.1038/nrmicro1177
  3. The role of mass spectrometry in plant systems biology vol.25, pp.2, 2006, https://doi.org/10.1002/mas.20063
  4. Correlative GC-TOF-MS-based metabolite profiling and LC-MS-based protein profiling reveal time-related systemic regulation of metabolite–protein networks and improve pattern recognition for multiple biomarker selection vol.1, pp.2, 2005, https://doi.org/10.1007/s11306-005-4430-9
  5. Integrated analysis of transcriptomics and metabolomics profiles vol.2, pp.5, 2008, https://doi.org/10.1517/17530059.2.5.497
  6. Development and application of proteomics technologies in Saccharomyces cerevisiae vol.23, pp.12, 2005, https://doi.org/10.1016/j.tibtech.2005.09.004
  7. All systems go: launching cell simulation fueled by integrated experimental biology data vol.16, pp.3, 2005, https://doi.org/10.1016/j.copbio.2005.04.004
  8. Metabolomics: from pattern recognition to biological interpretation vol.10, pp.22, 2005, https://doi.org/10.1016/S1359-6446(05)03609-3
  9. From genomes to systems: the path with yeast vol.361, pp.1467, 2006, https://doi.org/10.1098/rstb.2005.1805
  10. The metabolome 18 years on: a concept comes of age vol.12, pp.9, 2016, https://doi.org/10.1007/s11306-016-1108-4
  11. Profiling microbial metabolomes: what do we stand to gain? vol.1, pp.1, 2005, https://doi.org/10.1007/s11306-005-1104-6
  12. Improvement of Mitochondria Extract fromSaccharomyces cerevisiaeCharacterization in Shotgun Proteomics Using Sheathless Capillary Electrophoresis Coupled to Tandem Mass Spectrometry vol.54, pp.4, 2016, https://doi.org/10.1093/chromsci/bmw005
  13. Application of metabolome data in functional genomics: A conceptual strategy vol.7, pp.4, 2005, https://doi.org/10.1016/j.ymben.2005.05.003
  14. Measuring the metabolome: current analytical technologies vol.130, pp.5, 2005, https://doi.org/10.1039/b418288j
  15. The relative merits of the tetO2 andtetO7 promoter systems for the functional analysis of heterologous genes in yeast and a compilation of essential yeast genes withtetO2 promoter substitutions vol.23, pp.4, 2006, https://doi.org/10.1002/yea.1348
  16. Yeast systems biology to unravel the network of life vol.23, pp.3, 2006, https://doi.org/10.1002/yea.1357
  17. Yeast as a model eukaryote in toxinology: A functional genomics approach to studying the molecular basis of action of pharmacologically active molecules vol.60, pp.4, 2012, https://doi.org/10.1016/j.toxicon.2012.03.014
  18. Exometabolic and transcriptional response in relation to phenotype and gene copy number in respiration-related deletion mutants ofS. cerevisiae vol.25, pp.9, 2008, https://doi.org/10.1002/yea.1612
  19. Integration of metabolomics and proteomics in molecular plant physiology - coping with the complexity by data-dimensionality reduction vol.132, pp.2, 2008, https://doi.org/10.1111/j.1399-3054.2007.01011.x
  20. Metabolomic applications of electrochemistry/Mass spectrometry vol.15, pp.12, 2004, https://doi.org/10.1016/j.jasms.2004.08.016
  21. Understanding signaling in yeast: Insights from network analysis vol.97, pp.5, 2007, https://doi.org/10.1002/bit.21317
  22. Systems Biology and the Molecular Circuits of Cancer vol.5, pp.10, 2004, https://doi.org/10.1002/cbic.200400170
  23. Dynamics of Time-Lagged Gene-to-Metabolite Networks ofEscherichia coliElucidated by Integrative Omics Approach vol.15, pp.1-2, 2011, https://doi.org/10.1089/omi.2010.0074
  24. Experimental ‘omics’ data in tree research: facing complexity vol.26, pp.6, 2012, https://doi.org/10.1007/s00468-012-0777-5
  25. Mapping of sulfur metabolic pathway by LC Orbitrap mass spectrometry vol.721, 2012, https://doi.org/10.1016/j.aca.2012.01.050
  26. Metabolomics: an integral technique in systems biology vol.2, pp.4, 2010, https://doi.org/10.4155/bio.09.192
  27. Metabolic and stress adaptation by Mycosphaerella graminicola during sporulation in its host revealed through microarray transcription profiling vol.6, pp.5, 2005, https://doi.org/10.1111/j.1364-3703.2005.00304.x
  28. A systems biology perspective of wine fermentations vol.24, pp.11, 2007, https://doi.org/10.1002/yea.1545
  29. Green systems biology — From single genomes, proteomes and metabolomes to ecosystems research and biotechnology vol.75, pp.1, 2011, https://doi.org/10.1016/j.jprot.2011.07.010
  30. Genomes, phylogeny, and evolutionary systems biology vol.102, pp.Supplement 1, 2005, https://doi.org/10.1073/pnas.0501984102
  31. The Functional Genomics Experiment model (FuGE): an extensible framework for standards in functional genomics vol.25, pp.10, 2007, https://doi.org/10.1038/nbt1347
  32. Fuzzy association rules for biological data analysis: A case study on yeast vol.9, pp.1, 2008, https://doi.org/10.1186/1471-2105-9-107