Li S, Armstrong CM, Bertin N, Ge H, Milstein S, Boxem M, Vidalain PO, Han JD, Chesneau A, Hao T, Goldberg DS, Li N, Martinez M, Rual JF, Lamesch P, Xu L, Tewari M, Wong SL, Zhang LV, Berriz GF, Jacotot L, Vaglio P, Reboul J, Hirozane-Kishikawa T, Li Q, Gabel HW, Elewa A, Baumgartner B, Rose DJ, Yu H, Bosak S, Sequerra R, Fraser A, Mango SE, Saxton WM, Strome S, Van Den Heuvel S, Piano F, Vandenhaute J, Sardet C, Gerstein M, Doucette-Stamm L, Gunsalus KC, Harper JW, Cusick ME, Roth FP, Hill DE, Vidal M. A map of the interactome network of the metazoan C. elegans. Science. 2004 Jan 23;303(5657):540-3. PubMed.
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Comments
Although this paper represents a tremendous amount of work, it is not as strong a study as the similar one conduced recently in the fruit fly (Giot et al., 2003). Li et al. used only about one-fifth the number of bait targets as used in the fly work, so their interaction map is presumably less extensive than that constructed for the fly. Of more concern is the authors' own estimation that they have recapitulated only 10 percent of the already known interactions in their test set. The authors also make some comparisons between their data and the published C. elegans microarray data that don't seem compelling, although it is unclear if this indicates weaknesses in the data or a general lack of (biological) concurrence between protein interaction and transcriptional profiles.
The real question is whether the high-throughput protein interaction datasets are really useful for understanding disease-associated protein function and pathology. In a simple test, I looked for interactions found for the fly and worm homologues of APP; apparently, none were identified in the fly study, and one (questionable?) interaction was found in C. elegans. This is obviously a limited sample test, and I am certain there will be instances where insights will be gained from these interactome maps. However, I think these insights may occur more commonly for disease genes that aren't already well-studied.
References:
Giot L, Bader JS, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hao YL, Ooi CE, Godwin B, Vitols E, Vijayadamodar G, Pochart P, Machineni H, Welsh M, Kong Y, Zerhusen B, Malcolm R, Varrone Z, Collis A, Minto M, Burgess S, McDaniel L, Stimpson E, Spriggs F, Williams J, Neurath K, Ioime N, Agee M, Voss E, Furtak K, Renzulli R, Aanensen N, Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J, Stanyon CA, Finley RL, White KP, Braverman M, Jarvie T, Gold S, Leach M, Knight J, Shimkets RA, McKenna MP, Chant J, Rothberg JM. A protein interaction map of Drosophila melanogaster. Science. 2003 Dec 5;302(5651):1727-36. PubMed.
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