title: Towards a proteome-scale map of the human protein-protein interaction network.
abstract: Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, 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 approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 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.
authors.affiliation: Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rual
authors.forename: Kavitha
authors.initials: K
authors.lastname: Venkatesan
authors.forename: Tong
authors.initials: T
authors.lastname: Hao
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hirozane-Kishikawa
authors.forename: Amélie
authors.initials: A
authors.lastname: Dricot
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Gabriel F
authors.initials: GF
authors.lastname: Berriz
authors.forename: Francis D
authors.initials: FD
authors.lastname: Gibbons
authors.forename: Matija
authors.initials: M
authors.lastname: Dreze
authors.forename: Nono
authors.initials: N
authors.lastname: Ayivi-Guedehoussou
authors.forename: Niels
authors.initials: N
authors.lastname: Klitgord
authors.forename: Christophe
authors.initials: C
authors.lastname: Simon
authors.forename: Mike
authors.initials: M
authors.lastname: Boxem
authors.forename: Stuart
authors.initials: S
authors.lastname: Milstein
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rosenberg
authors.forename: Debra S
authors.initials: DS
authors.lastname: Goldberg
authors.forename: Lan V
authors.initials: LV
authors.lastname: Zhang
authors.forename: Sharyl L
authors.initials: SL
authors.lastname: Wong
authors.forename: Giovanni
authors.initials: G
authors.lastname: Franklin
authors.forename: Siming
authors.initials: S
authors.lastname: Li
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Albala
authors.forename: Janghoo
authors.initials: J
authors.lastname: Lim
authors.forename: Carlene
authors.initials: C
authors.lastname: Fraughton
authors.forename: Estelle
authors.initials: E
authors.lastname: Llamosas
authors.forename: Sebiha
authors.initials: S
authors.lastname: Cevik
authors.forename: Camille
authors.initials: C
authors.lastname: Bex
authors.forename: Philippe
authors.initials: P
authors.lastname: Lamesch
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sikorski
authors.forename: Jean
authors.initials: J
authors.lastname: Vandenhaute
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: Alex
authors.initials: A
authors.lastname: Smolyar
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bosak
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Sequerra
authors.forename: Lynn
authors.initials: L
authors.lastname: Doucette-Stamm
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cusick
authors.forename: David E
authors.initials: DE
authors.lastname: Hill
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Roth
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
mesh_terms: D003001:Cloning, Molecular; D006801:Humans; D016366:Open Reading Frames / Q000235:genetics; D011485:Protein Binding; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D020798:Two-Hybrid System Techniques
chemical_list: D020543:Proteome; D012313:RNA