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Originally published in Science Express on 6 November 2003
Science 5 December 2003:
Vol. 302. no. 5651, pp. 1727 - 1736
DOI: 10.1126/science.1090289
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Research Articles

A Protein Interaction Map of Drosophila melanogaster

L. Giot,1* J. S. Bader,1*{dagger} 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,2 C. A. Stanyon,2 R. L. Finley, Jr.,2 K. P. White,3 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{ddagger} J. M. Rothberg1

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.

1 CuraGen Corporation, 555 Long Wharf Drive, New Haven, CT 06511, USA.
2 Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.
3 Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.


* These authors contributed equally to this work.

{dagger} Present address: Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21215, USA.

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

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