Towards a proteome-scale map of the human protein–protein interaction network

Jean-François Rual, Kavitha Venkatesan, Tong Hao, Tomoko Hirozane-Kishikawa, Amélie Dricot, Ning Li, Gabriel F. Berriz, Francis D. Gibbons, Matija Dreze, Nono Ayivi-Guedehoussou, Niels Klitgord, Christophe Simon, Mike Boxem, Stuart Milstein, Jennifer Rosenberg, Debra S. Goldberg, Lan V. Zhang, Sharyl L. Wong, Giovanni Franklin, Siming Li, Joanna S. Albala, Janghoo Lim, Carlene Fraughton, Estelle Llamosas, Sebiha Cevik, Camille Bex, Philippe Lamesch, Robert S. Sikorski, Jean Vandenhaute, Huda Y. Zoghbi, Alex Smolyar, Stephanie Bosak, Reynaldo Sequerra, Lynn Doucette-Stamm, Michael E. Cusick, David E. Hill (), Frederick P. Roth () and Marc Vidal ()
Additional contact information
Jean-François Rual: Harvard Medical School
Kavitha Venkatesan: Harvard Medical School
Tong Hao: Harvard Medical School
Tomoko Hirozane-Kishikawa: Harvard Medical School
Amélie Dricot: Harvard Medical School
Ning Li: Harvard Medical School
Gabriel F. Berriz: Harvard Medical School
Francis D. Gibbons: Harvard Medical School
Matija Dreze: Harvard Medical School
Nono Ayivi-Guedehoussou: Harvard Medical School
Niels Klitgord: Harvard Medical School
Christophe Simon: Harvard Medical School
Mike Boxem: Harvard Medical School
Stuart Milstein: Harvard Medical School
Jennifer Rosenberg: Harvard Medical School
Debra S. Goldberg: Harvard Medical School
Lan V. Zhang: Harvard Medical School
Sharyl L. Wong: Harvard Medical School
Giovanni Franklin: Harvard Medical School
Siming Li: Harvard Medical School
Joanna S. Albala: Harvard Medical School
Janghoo Lim: Baylor College of Medicine
Carlene Fraughton: Harvard Medical School
Estelle Llamosas: Harvard Medical School
Sebiha Cevik: Harvard Medical School
Camille Bex: Harvard Medical School
Philippe Lamesch: Harvard Medical School
Robert S. Sikorski: Arcbay, Inc.
Jean Vandenhaute: Unité de Recherche en Biologie Moléculaire, Facultés Notre-Dame de la Paix
Huda Y. Zoghbi: Baylor College of Medicine
Alex Smolyar: Harvard Medical School
Stephanie Bosak: Agencourt Bioscience Corporation
Reynaldo Sequerra: Agencourt Bioscience Corporation
Lynn Doucette-Stamm: Agencourt Bioscience Corporation
Michael E. Cusick: Harvard Medical School
David E. Hill: Harvard Medical School
Frederick P. Roth: Harvard Medical School
Marc Vidal: Harvard Medical School

Nature, 2005, vol. 437, issue 7062, 1173-1178

Abstract: Abstract Systematic mapping of protein–protein interactions, or ‘interactome’ mapping, was initiated in model organisms, starting with defined biological processes1,2 and then expanding to the scale of the proteome3,4,5,6,7. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties8,9, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein–protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of ∼8,100 currently available Gateway-cloned open reading frames and detected ∼2,800 interactions. This data set, called CCSB-HI1, has a verification rate of ∼78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by ∼70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.

Date: 2005
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DOI: 10.1038/nature04209

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