For over half a century it has been conjectured that macromolecules form complex networks of functionally interacting components, and that the molecular mechanisms underlying most biological processes correspond to particular steady states adopted by such cellular networks. However, until recently, systems-level theoretical conjectures remained largely unappreciated, mainly because of lack of supporting experimental data.
To generate the information necessary to eventually address how complex cellular networks relate to biology, we initiated, at the scale of the whole proteome, an integrated approach for modeling protein-protein interaction or “interactome” networks. Our main questions are: How are interactome networks organized at the scale of the whole cell? How can we uncover local and global features underlying this organization, and how are interactome networks modified in human disease, such as cancer?
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References:
- Han JD, Bertin N, Hao T, Goldberg DS, Berriz GF, Zhang LV, Dupuy D, Walhout AJ, Cusick ME, Roth FP, Vidal M. Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature 2004;430:88-93.
- Gunsalus KC, Ge H, Schetter AJ, Goldberg DS, Han JD, Hao T, Bertin N, Li N, Huang J, Chuang LS, Mani R, Berriz G, Hyman AA, Sonnichsen B, Echeverri CJ, Roth FP*, Vidal M*, Piano F*. Predictive models of molecular machines involved in C. elegans early embryogenesis. Nature 2005;436:861-5 (* = co-corresponding authors).
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE*, Roth FP*, Vidal M*. Towards a proteome-scale map of the human protein-protein interaction network. Nature 2005;437:1173-8 (* = co-corresponding authors).
- Dupuy D, Bertin N, Hildalgo CA, Venkatesan K, Tu D, Lee D, Rosenberg J, Svrzikapa N, Blanc A, Carnec A, Carvunis AR, Pulak R, Shingles J, Reece-Hoyes J, Newbury R, Viveiros R, Mohler WA, Tasan M, Roth FP, Le Peuch C, Hope IA, Johnsen R, Moerman D, Barabasi AL*, Baillie D*, Vidal M*. Genome-scale analysis of Caenorhabditis elegans spatial and temporal gene expression patterns during post-embryonic development. Nat Biotechnol 2007; in press (* = co-corresponding authors).
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