Reference: Szappanos B, et al. (2011) An integrated approach to characterize genetic interaction networks in yeast metabolism. Nat Genet 43(7):656-62

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Abstract


Although experimental and theoretical efforts have been applied to globally map genetic interactions, we still do not understand how gene-gene interactions arise from the operation of biomolecular networks. To bridge the gap between empirical and computational studies, we i, quantitatively measured genetic interactions between ∼185,000 metabolic gene pairs in Saccharomyces cerevisiae, ii, superposed the data on a detailed systems biology model of metabolism and iii, introduced a machine-learning method to reconcile empirical interaction data with model predictions. We systematically investigated the relative impacts of functional modularity and metabolic flux coupling on the distribution of negative and positive genetic interactions. We also provide a mechanistic explanation for the link between the degree of genetic interaction, pleiotropy and gene dispensability. Last, we show the feasibility of automated metabolic model refinement by correcting misannotations in NAD biosynthesis and confirming them by in vivo experiments.

Reference Type
Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
Authors
Szappanos B, Kovács K, Szamecz B, Honti F, Costanzo M, Baryshnikova A, Gelius-Dietrich G, Lercher MJ, Jelasity M, Myers CL, ... Show all
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Interaction Annotations


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Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations


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

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