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An integrated approach to characterize genetic interaction networks in yeast metabolism

Szappanos, Balázs and Kovács, Károly and Szamecz, Béla and Honti, Frantisek and Costanzo, Michael and Jelasity, Márk and Pál, Csaba and Papp, Balázs (2011) An integrated approach to characterize genetic interaction networks in yeast metabolism. NATURE GENETICS, 43 (7). pp. 656-662. ISSN 1061-4036

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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 similar to 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.

Item Type: Article
Uncontrolled Keywords: Epistasis; LANDSCAPE; ORGANIZATION; RECONSTRUCTIONS; BIOLOGY; SCALE; DELETION MUTANTS; ESCHERICHIA-COLI; BIOCHEMICAL NETWORKS; SACCHAROMYCES-CEREVISIAE GENOME
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH426 Genetics / genetika, örökléstan
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 22 May 2018 14:20
Last Modified: 22 May 2018 14:20
URI: http://real.mtak.hu/id/eprint/79943

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