title: Co-Expression Network Models Suggest that Stress Increases Tolerance to Mutations.
abstract: Network models are a well established tool for studying the robustness of complex systems, including modelling the effect of loss of function mutations in protein interaction networks. Past work has concentrated on average damage caused by random node removal, with little attention to the shape of the damage distribution. In this work, we use fission yeast co-expression networks before and after exposure to stress to model the effect of stress on mutational robustness. We find that exposure to stress decreases the average damage from node removal, suggesting stress induces greater tolerance to loss of function mutations. The shape of the damage distribution is also changed upon stress, with a greater incidence of extreme damage after exposure to stress. We demonstrate that the change in shape of the damage distribution can have considerable functional consequences, highlighting the need to consider the damage distribution in addition to average behaviour.
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College, St Mary's Campus, Norfolk Place, London W2 1PG, UK.|University College London, ISMB, London, WC1E 6BT, UK.
authors.forename: Sonja
authors.initials: S
authors.lastname: Lehtinen
authors.affiliation: University College London, GEE, London, WC1E 6BT, UK.
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
authors.affiliation: University College London, ISMB, London, WC1E 6BT, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Orengo
mesh_terms: D008962:Models, Theoretical; D009154:Mutation; D060066:Protein Interaction Maps / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological