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A Protein Interaction Map of Drosophila melanogaster

2003; American Association for the Advancement of Science; Volume: 302; Issue: 5651 Linguagem: Inglês

10.1126/science.1090289

1095-9203

Loïc Giot, Joel S. Bader, Cory Brouwer, Arunima Chaudhuri, Baizeng Kuang, Y. Li, Yameng Hao, Clara Ooi, Brian C. Godwin, E. Vitols, Govindan Vijayadamodar, Pascale Pochart, H. Machineni, Michael J. Welsh, Yong Kong, B. Zerhusen, Rachel D. Malcolm, Z. Varrone, Andrew J. Collis, M. Minto, Shane C. Burgess, L. Patrice McDaniel, Eric E. Stimpson, Frank Spriggs, Jessica F. Williams, K. Neurath, N. Ioime, Michelle Agee, Edward Z. Voss, Krystyna Furtak, R. Renzulli, N. Aanensen, S. Carrolla, E. Bickelhaupt, Y. Lazovatsky, Alexandre J. da Silva, Jiancheng Zhong, Clement A. Stanyon, Russell L. Finley, Kevin P. White, Michael Braverman, Thomas Jarvie, Stephen J. Gold, Martin Leach, James Knight, Richard A. Shimkets, Michael P. McKenna, John Chant, Jonathan M. Rothberg,

Computational Drug Discovery Methods

Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.