Systematic prediction of human membrane receptor interactions.
Membrane receptor-activated signal transduction pathways are integral to cellular functions and disease mechanisms in humans. Identification of the full set of proteins interacting with membrane receptors by high-throughput experimental means is difficult because methods to directly identify protein interactions are largely not applicable to membrane proteins. Unlike prior approaches that attempted to predict the global human interactome, we used a computational strategy that only focused on discovering the interacting partners of human membrane receptors leading to improved results for these proteins. We predict specific interactions based on statistical integration of biological data containing highly informative direct and indirect evidences together with feedback from experts. The predicted membrane receptor interactome provides a system-wide view, and generates new biological hypotheses regarding interactions between membrane receptors and other proteins. We have experimentally validated a number of these interactions. The results suggest that a framework of systematically integrating computational predictions, global analyses, biological experimentation and expert feedback is a feasible strategy to study the human membrane receptor interactome.
Qi
Yanjun
Y
School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA.
Dhiman
Harpreet K
HK
Bhola
Neil
N
Budyak
Ivan
I
Kar
Siddhartha
S
Man
David
D
Dutta
Arpana
A
Tirupula
Kalyan
K
Carr
Brian I
BI
Grandis
Jennifer
J
Bar-Joseph
Ziv
Z
Klein-Seetharaman
Judith
J
D019295:Computational Biology / Q000379:methods*; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism; D006801:Humans; D025941:Protein Interaction Mapping / Q000379:methods*; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism*; D015398:Signal Transduction; D049490:Systems Biology / Q000379:methods
D020543:Proteome; D011956:Receptors, Cell Surface; C512478:EGFR protein, human; D066246:ErbB Receptors