Reference: Hannum G, et al. (2009) Genome-wide association data reveal a global map of genetic interactions among protein complexes. PLoS Genet 5(12):e1000782

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Abstract


This work demonstrates how gene association studies can be analyzed to map a global landscape of genetic interactions among protein complexes and pathways. Despite the immense potential of gene association studies, they have been challenging to analyze because most traits are complex, involving the combined effect of mutations at many different genes. Due to lack of statistical power, only the strongest single markers are typically identified. Here, we present an integrative approach that greatly increases power through marker clustering and projection of marker interactions within and across protein complexes. Applied to a recent gene association study in yeast, this approach identifies 2,023 genetic interactions which map to 208 functional interactions among protein complexes. We show that such interactions are analogous to interactions derived through reverse genetic screens and that they provide coverage in areas not yet tested by reverse genetic analysis. This work has the potential to transform gene association studies, by elevating the analysis from the level of individual markers to global maps of genetic interactions. As proof of principle, we use synthetic genetic screens to confirm numerous novel genetic interactions for the INO80 chromatin remodeling complex.

Reference Type
Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, Non-P.H.S.
Authors
Hannum G, Srivas R, Guénolé A, van Attikum H, Krogan NJ, Karp RM, Ideker T
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Gene Ontology Annotations


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Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

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Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

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Gene Species Gene ID Strain background Direction Details Source Reference