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Published Online November 6, 2003
Science DOI: 10.1126/science.1090289

Research Articles

Submitted on August 11, 2003
Accepted on October 29, 2003

A Protein Interaction Map of Drosophila melanogaster

L. Giot 1, J. S. Bader 2, C. Brouwer 1, A. Chaudhuri 1, B. Kuang 1, Y. Li 1, Y. L. Hao 1, C. E. Ooi 1, B. Godwin 1, E. Vitols 1, G. Vijayadamodar 1, P. Pochart 1, H. Machineni 1, M. Welsh 1, Y. Kong 1, B. Zerhusen 1, R. Malcolm 1, Z. Varrone 1, A. Collis 1, M. Minto 1, S. Burgess 1, L. McDaniel 1, E. Stimpson 1, F. Spriggs 1, J. Williams 1, K. Neurath 1, N. Ioime 1, M. Agee 1, E. Voss 1, K. Furtak 1, R. Renzulli 1, N. Aanensen 1, S. Carrolla 1, E. Bickelhaupt 1, Y. Lazovatsky 1, A. DaSilva 1, J. Zhong 3, C. A. Stanyon 3, R. L. Finley Jr. 3, K. P. White 4, M. Braverman 1, T. Jarvie 1, S. Gold 1, M. Leach 1, J. Knight 1, R. A. Shimkets 1, M. P. McKenna 1, J. Chant 1*, J. M. Rothberg 1

1 CuraGen Corporation, 555 Long Wharf Drive, New Haven, CT 06511, USA.
2 CuraGen Corporation, 555 Long Wharf Drive, New Haven, CT 06511, USA; Present Address: Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21215, USA.
3 Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.
4 Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.

* To whom correspondence should be addressed. E-mail: jchant{at}curagen.com.

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.


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