TY - JOUR AU - Qi, Y. AU - Dhiman, H.K. AU - Bhola, N.E. AU - Budyak, I. AU - Kar, S. AU - Man, D. AU - Dutta, A. AU - Tirupula, K. AU - Carr, B. AU - Grandis, J.R. AU - Bar-Joseph, Z. AU - Klein-Seetharaman, J. TI - Systematic prediction of human membrane receptor interactions JO - Proteomics VL - 9 SN - 1615-9853 CY - Weinheim PB - Wiley VCH M1 - PreJuSER-8400 SP - 5243 - 5255 PY - 2009 N1 - This work was supported in part by National Science Foundation Grants ITR 0225656, CAREER 0448453 and CAREER CC044917, National Institutes of Health Grants NLM108730, R01 CA098372 and AI060422 and the Sofya Kovalvskaya Award (to J. K. S.) from the Humboldt Foundation. AB - 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. KW - Computational Biology: methods KW - Humans KW - Protein Interaction Mapping: methods KW - Proteome: analysis KW - Proteome: metabolism KW - Proteomics: methods KW - Receptor, Epidermal Growth Factor: analysis KW - Receptor, Epidermal Growth Factor: metabolism KW - Receptors, Cell Surface: analysis KW - Receptors, Cell Surface: metabolism KW - Signal Transduction KW - Systems Biology: methods KW - Proteome (NLM Chemicals) KW - Receptors, Cell Surface (NLM Chemicals) KW - EGFR protein, human (NLM Chemicals) KW - Receptor, Epidermal Growth Factor (NLM Chemicals) KW - J (WoSType) LB - PUB:(DE-HGF)16 C6 - pmid:19798668 C2 - pmc:PMC3076061 UR - <Go to ISI:>//WOS:000273393900006 DO - DOI:10.1002/pmic.200900259 UR - https://juser.fz-juelich.de/record/8400 ER -