A Protein Interaction Map of Drosophila melanogaster

American Association for the Advancement of Science (AAAS) - Tập 302 Số 5651 - Trang 1727-1736 - 2003
Loïc Giot1,2,3, Joel S. Bader1,2,3, Cory Brouwer1,2,3, Arunima Chaudhuri1,2,3, Bing Kuang1,2,3, Y. Li1,2,3, Yameng Hao1,2,3, Clara Ooi1,2,3, Brian C. Godwin1,2,3, E. Vitols1,2,3, Govindan Vijayadamodar1,2,3, Pascale Pochart1,2,3, H. Machineni1,2,3, Michael J. Welsh1,2,3, Yong Kong1,2,3, B. Zerhusen1,2,3, Rachel D. Malcolm1,2,3, Z. Varrone1,2,3, Andrew J. Collis1,2,3, M. Minto1,2,3, Shane C. Burgess1,2,3, L. Patrice McDaniel1,2,3, Eric E. Stimpson1,2,3, Frank Spriggs1,2,3, Jessica F. Williams1,2,3, K. Neurath1,2,3, N. Ioime1,2,3, Michelle Agee1,2,3, Edward Z. Voss1,2,3, Krystyna Furtak1,2,3, R. Renzulli1,2,3, N. Aanensen1,2,3, S. Carrolla1,2,3, E. Bickelhaupt1,2,3, Y. Lazovatsky1,2,3, Alexandre J. da Silva1,2,3, Jiancheng Zhong1,1,3, Clement A. Stanyon1,1,3, Russell L. Finley1,1,3, Kevin P. White1,3,4, Michael Braverman1,2,3, Thomas Jarvie1,2,3, Stephen J. Gold1,2,3, Martin Leach1,2,3, James Knight1,2,3, Richard A. Shimkets1,2,3, Michael P. McKenna1,2,3, John Chant1,2,3, Jonathan M. Rothberg1,2,3
1Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA
2CuraGen Corporation, 555 Long Wharf Drive, New Haven, CT 06511, USA,
3Department of Genetics, Yale University School of Medicine, New Haven, CT 06520 USA
4Dept. of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.

Tóm tắt

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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We thank our colleagues at CuraGen in particular those in the genomics facility who performed all the sequencing and prepared the cDNA libraries described in this work. We also thank S. Hossain and members of the Finley laboratory for technical assistance with Drosophila cultures and RNA preparations. J.Z. C.A.S and R.L.F. were supported by NIH grant HG01536 (to R.L.F.). The interactions are also available at our Web sites www.curagen.com and www.jhubiomed.org.