Abstract
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Highlights
IntroductionGene-gene interactions – the epistatic influences of one gene’s effect on the function of another gene – have widespread effects on cellular and organismal phenotypes, ranging from fitness defects in unicellular organisms to interactions between germline and somatic variants in cancer (Baryshnikova et al, 2013; Billmann and Boutros, 2017; Boone et al, 2007; Burgess, 2016; Carter et al, 2017; Ideker and Krogan, 2012; Mani et al, 2008; Phillips, 2008; Taylor and Ehrenreich, 2015)
The wiring diagrams of genetic interaction networks were studied at steady state conditions between two endpoints
Often, when genetic interactions such as a synthetic sick or lethal interaction between two genes are quantified, different interactions-scores (p) are found at different time points (Figure 1B). This indicates that, next to a perturbation by external stresses, time influences the experimental outcome of genetic interaction measurements systematically
Summary
Gene-gene interactions – the epistatic influences of one gene’s effect on the function of another gene – have widespread effects on cellular and organismal phenotypes, ranging from fitness defects in unicellular organisms to interactions between germline and somatic variants in cancer (Baryshnikova et al, 2013; Billmann and Boutros, 2017; Boone et al, 2007; Burgess, 2016; Carter et al, 2017; Ideker and Krogan, 2012; Mani et al, 2008; Phillips, 2008; Taylor and Ehrenreich, 2015). Statistical genetic interactions ( referred to as genetic interactions) have been defined as an unexpected phenotypic outcome observed upon simultaneous perturbations (or knock-outs) of two genes that cannot be explained from the genes’ individual effects (Beltrao et al, 2010; Fisher, 1930; Mani et al, 2008). Genetic interactions can be discovered using pairwise perturbations of genes, a strategy which has been experimentally used at large scale in yeast (Collins et al, 2007; Costanzo et al, 2010; Fiedler et al, 2009; Tong et al, 2001), C. elegans (Lehner et al, 2006), Drosophila (Fischer et al, 2015; Horn et al, 2011), E. coli (Babu et al, 2011) and human cells (Kampmann et al, 2013; Laufer et al, 2013; Roguev et al, 2013; Shen et al, 2017).
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