Towards a proteome-scale map of the human protein-protein interaction network.
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.
Rual
Jean-François
JF
Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
Venkatesan
Kavitha
K
Hao
Tong
T
Hirozane-Kishikawa
Tomoko
T
Dricot
Amélie
A
Li
Ning
N
Berriz
Gabriel F
GF
Gibbons
Francis D
FD
Dreze
Matija
M
Ayivi-Guedehoussou
Nono
N
Klitgord
Niels
N
Simon
Christophe
C
Boxem
Mike
M
Milstein
Stuart
S
Rosenberg
Jennifer
J
Goldberg
Debra S
DS
Zhang
Lan V
LV
Wong
Sharyl L
SL
Franklin
Giovanni
G
Li
Siming
S
Albala
Joanna S
JS
Lim
Janghoo
J
Fraughton
Carlene
C
Llamosas
Estelle
E
Cevik
Sebiha
S
Bex
Camille
C
Lamesch
Philippe
P
Sikorski
Robert S
RS
Vandenhaute
Jean
J
Zoghbi
Huda Y
HY
Smolyar
Alex
A
Bosak
Stephanie
S
Sequerra
Reynaldo
R
Doucette-Stamm
Lynn
L
Cusick
Michael E
ME
Hill
David E
DE
Roth
Frederick P
FP
Vidal
Marc
M
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
D020543:Proteome; D012313:RNA