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Science 303 (5657): 540-543

Copyright © 2004 by the American Association for the Advancement of Science

A Map of the Interactome Network of the Metazoan C. elegans

Siming Li,1* Christopher M. Armstrong,1* Nicolas Bertin,1* Hui Ge,1* Stuart Milstein,1* Mike Boxem,1* Pierre-Olivier Vidalain,1* Jing-Dong J. Han,1* Alban Chesneau,1,2* Tong Hao,1 Debra S. Goldberg,3 Ning Li,1 Monica Martinez,1 Jean-François Rual,1,4 Philippe Lamesch,1,4 Lai Xu,5{dagger} Muneesh Tewari,1 Sharyl L. Wong,3 Lan V. Zhang,3 Gabriel F. Berriz,3 Laurent Jacotot,1{ddagger} Philippe Vaglio,1{ddagger} Jérôme Reboul,1§ Tomoko Hirozane-Kishikawa,1 Qianru Li,1 Harrison W. Gabel,1 Ahmed Elewa,1|| Bridget Baumgartner,5 Debra J. Rose,6 Haiyuan Yu,7 Stephanie Bosak,8 Reynaldo Sequerra,8 Andrew Fraser,9 Susan E. Mango,10 William M. Saxton,6 Susan Strome,6 Sander van den Heuvel,11 Fabio Piano,12 Jean Vandenhaute,4 Claude Sardet,2 Mark Gerstein,7 Lynn Doucette-Stamm,8 Kristin C. Gunsalus,12 J. Wade Harper,5{dagger} Michael E. Cusick,1 Frederick P. Roth,3 David E. Hill,1 Marc Vidal1#

Abstract: To initiate studies on how protein-protein interaction (or "interactome") networks relate to multicellular functions, we have mapped a large fraction of the Caenorhabditis elegans interactome network. Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity purification assays experimentally validated the overall quality of this Y2H data set. Together with already described Y2H interactions and interologs predicted in silico, the current version of the Worm Interactome (WI5) map contains ~5500 interactions. Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses.

1 Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
2 Institut de Génétique Moléculaire, Centre National de la Recherche Scientifique UMR 5535, 1919 Route de Mende, 34293 Montpellier Cedex 5, France.
3 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
4 Unité de Recherche en Biologie Moléculaire, Facultés Notre-Dame de la Paix, 61 Rue de Bruxelles, 5000 Namur, Belgium.
5 Verna and Marrs Department of Biochemistry and Molecular Biology, Program in Cell and Molecular Biology, Biophysics, and Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
6 Department of Biology, Indiana University, Jordan Hall 142, 1001 East Third Street, Bloomington, IN 47405, USA.
7 Department of Molecular Biophysics and Biochemistry and Department of Computer Science, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA.
8 Agencourt Bioscience Corporation, 100 Cummings Center, Suite 107G, Beverly, MA 01915, USA.
9 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
10 Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
11 Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129, USA.
12 Department of Biology, New York University, 1009 Silver Building, 100 Washington Square East, New York, NY 10003, USA.

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* These authors contributed equally to this work.

{dagger} Present address: Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.

{ddagger} Present address: Modul-Bio, 232 Boulevard Sainte-Marguerite, 13009 Marseille, France.

§ Present address: INSERM, Unité 119, Institut Paoli Calmettes, 13009 Marseille, France.

|| Present address: Program in Gene Function and Expression, University of Massachusetts, 55 Lake Avenue, North Worcester, MA 01605, USA.

Present address: Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

# To whom correspondence should be addressed. E-mail: marc_vidal{at}dfci.harvard.edu.


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Computational Identification of Potential Molecular Interactions in Arabidopsis.
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Plant Physiology 151, 34-46
   Abstract »    Full Text »    PDF »
Identifying the topology of protein complexes from affinity purification assays.
C. C. Friedel and R. Zimmer (2009)
Bioinformatics 25, 2140-2146
   Abstract »    Full Text »    PDF »
Using RNA Interference to Identify Specific Modifiers of a Temperature-Sensitive, Embryonic-Lethal Mutation in the Caenorhabditis elegans Ubiquitin-Like Nedd8 Protein Modification Pathway E1-Activating Gene rfl-1.
M. Dorfman, J.-E. Gomes, S. O'Rourke, and B. Bowerman (2009)
Genetics 182, 1035-1049
   Abstract »    Full Text »    PDF »
A complex-centric view of protein network evolution.
N. Yosef, M. Kupiec, E. Ruppin, and R. Sharan (2009)
Nucleic Acids Res. 37, e88
   Abstract »    Full Text »    PDF »
SNOW, a web-based tool for the statistical analysis of protein-protein interaction networks.
P. Minguez, S. Gotz, D. Montaner, F. Al-Shahrour, and J. Dopazo (2009)
Nucleic Acids Res. 37, W109-W114
   Abstract »    Full Text »    PDF »
Global networks of functional coupling in eukaryotes from comprehensive data integration.
A. Alexeyenko and E. L.L. Sonnhammer (2009)
Genome Res. 19, 1107-1116
   Abstract »    Full Text »    PDF »
Deciphering Signaling Outcomes from a System of Complex Networks.
R. C. Hsueh, M. Natarajan, I. Fraser, B. Pond, J. Liu, S. Mumby, H. Han, L. I. Jiang, M. I. Simon, R. Taussig, et al. (2009)
Science Signaling 2, ra22
   Abstract »    Full Text »    PDF »
Progress and challenges in predicting protein-protein interaction sites.
I. Ezkurdia, L. Bartoli, P. Fariselli, R. Casadio, A. Valencia, and M. L. Tress (2009)
Brief Bioinform 10, 233-246
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The ALP-Enigma Protein ALP-1 Functions in Actin Filament Organization to Promote Muscle Structural Integrity in Caenorhabditis elegans.
H.-F. Han and M. C. Beckerle (2009)
Mol. Biol. Cell 20, 2361-2370
   Abstract »    Full Text »    PDF »
Control of Rapsyn Stability by the CUL-3-containing E3 Ligase Complex.
S. Nam, K. Min, H. Hwang, H.-o. Lee, J. H. Lee, J. Yoon, H. Lee, S. Park, and J. Lee (2009)
J. Biol. Chem. 284, 8195-8206
   Abstract »    Full Text »    PDF »

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