Large-scale mapping of human protein-protein interactions by mass spectrometry.
Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.
Ewing
Rob M
RM
Protana, Toronto, Ontario, Canada.
Chu
Peter
P
Elisma
Fred
F
Li
Hongyan
H
Taylor
Paul
P
Climie
Shane
S
McBroom-Cerajewski
Linda
L
Robinson
Mark D
MD
O'Connor
Liam
L
Li
Michael
M
Taylor
Rod
R
Dharsee
Moyez
M
Ho
Yuen
Y
Heilbut
Adrian
A
Moore
Lynda
L
Zhang
Shudong
S
Ornatsky
Olga
O
Bukhman
Yury V
YV
Ethier
Martin
M
Sheng
Yinglun
Y
Vasilescu
Julian
J
Abu-Farha
Mohamed
M
Lambert
Jean-Philippe
JP
Duewel
Henry S
HS
Stewart
Ian I
II
Kuehl
Bonnie
B
Hogue
Kelly
K
Colwill
Karen
K
Gladwish
Katharine
K
Muskat
Brenda
B
Kinach
Robert
R
Adams
Sally-Lin
SL
Moran
Michael F
MF
Morin
Gregg B
GB
Topaloglou
Thodoros
T
Figeys
Daniel
D
D006801:Humans; D047468:Immunoprecipitation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D011506:Proteins