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Genome Biology

, 9:R135

First Online: 12 September 2008Received: 11 July 2008Accepted: 12 September 2008


BackgroundSynthetic lethality defines a genetic interaction where the combination of mutations in two or more genes leads to cell death. The implications of synthetic lethal screens have been discussed in the context of drug development as synthetic lethal pairs could be used to selectively kill cancer cells, but leave normal cells relatively unharmed. A challenge is to assess genome-wide experimental data and integrate the results to better understand the underlying biological processes. We propose statistical and computational tools that can be used to find relationships between synthetic lethality and cellular organizational units.

ResultsIn Saccharomyces cerevisiae, we identified multi-protein complexes and pairs of multi-protein complexes that share an unusually high number of synthetic genetic interactions. As previously predicted, we found that synthetic lethality can arise from subunits of an essential multi-protein complex or between pairs of multi-protein complexes. Finally, using multi-protein complexes allowed us to take into account the pleiotropic nature of the gene products.

ConclusionsModeling synthetic lethality using current estimates of the yeast interactome is an efficient approach to disentangle some of the complex molecular interactions that drive a cell. Our model in conjunction with applied statistical methods and computational methods provides new tools to better characterize synthetic genetic interactions.

AbbreviationsGOGene Ontology

MIPSMunich Information Center for Protein Sequences

SGAsynthetic genetic array.

Electronic supplementary materialThe online version of this article doi:10.1186-gb-2008-9-9-r135 contains supplementary material, which is available to authorized users.

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Autor: Nolwenn Le Meur - Robert Gentleman


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