title: An integrated approach to characterize genetic interaction networks in yeast metabolism.
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.
authors.affiliation: Institute of Biochemistry, Biological Research Centre, Szeged, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Szappanos
authors.forename: Károly
authors.initials: K
authors.lastname: Kovács
authors.forename: Béla
authors.initials: B
authors.lastname: Szamecz
authors.forename: Frantisek
authors.initials: F
authors.lastname: Honti
authors.forename: Michael
authors.initials: M
authors.lastname: Costanzo
authors.forename: Anastasia
authors.initials: A
authors.lastname: Baryshnikova
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gelius-Dietrich
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lercher
authors.forename: Márk
authors.initials: M
authors.lastname: Jelasity
authors.forename: Chad L
authors.initials: CL
authors.lastname: Myers
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Andrews
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Oliver
authors.forename: Csaba
authors.initials: C
authors.lastname: Pál
authors.forename: Balázs
authors.initials: B
authors.lastname: Papp
mesh_terms: D001185:Artificial Intelligence; D019295:Computational Biology; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins