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  A systematic Mammalian genetic interaction map reveals pathways underlying ricin susceptibility.

Bassik, M. C., Kampmann, M., Lebbink, R. J., Wang, S., Hein, M. Y., Poser, I., et al. (2013). A systematic Mammalian genetic interaction map reveals pathways underlying ricin susceptibility. Cell, 152(4), 909-922.

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 Creators:
Bassik, Michael C, Author
Kampmann, Martin, Author
Lebbink, Robert Jan, Author
Wang, Shuyi, Author
Hein, Marco Y, Author
Poser, Ina1, Author           
Weibezahn, Jimena, Author
Horlbeck, Max A, Author
Chen, Siyuan, Author
Mann, Matthias, Author
Hyman, Anthony A.1, Author           
Leproust, Emily M, Author
McManus, Michael T, Author
Weissman, Jonathan S.2, Author
Affiliations:
1Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              
2Max Planck Society, ou_persistent13              

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 Abstract: Genetic interaction (GI) maps, comprising pairwise measures of how strongly the function of one gene depends on the presence of a second, have enabled the systematic exploration of gene function in microorganisms. Here, we present a two-stage strategy to construct high-density GI maps in mammalian cells. First, we use ultracomplex pooled shRNA libraries (25 shRNAs/gene) to identify high-confidence hit genes for a given phenotype and effective shRNAs. We then construct double-shRNA libraries from these to systematically measure GIs between hits. A GI map focused on ricin susceptibility broadly recapitulates known pathways and provides many unexpected insights. These include a noncanonical role for COPI, a previously uncharacterized protein complex affecting toxin clearance, a specialized role for the ribosomal protein RPS25, and functionally distinct mammalian TRAPP complexes. The ability to rapidly generate mammalian GI maps provides a potentially transformative tool for defining gene function and designing combination therapies based on synergistic pairs.

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 Dates: 2013
 Publication Status: Issued
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 Rev. Type: -
 Identifiers: eDoc: 688478
Other: 5201
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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 152 (4) Sequence Number: - Start / End Page: 909 - 922 Identifier: -