252 research outputs found
Identification of response-modulated genetic interactions by sensitivity-based epistatic analysis
<p>Abstract</p> <p>Background</p> <p>High-throughput genomics has enabled the global mapping of genetic interactions based on the phenotypic impact of combinatorial genetic perturbations. An important next step is to understand how these networks are dynamically remodelled in response to environmental stimuli. Here, we report on the development and testing of a method to identify such interactions. The method was developed from first principles by treating the impact on cellular growth of environmental perturbations equivalently to that of gene deletions. This allowed us to establish a novel neutrality function marking the absence of epistasis in terms of sensitivity phenotypes rather than fitness. We tested the method by identifying fitness- and sensitivity-based interactions involved in the response to drug-induced DNA-damage of budding yeast <it>Saccharomyces cerevisiae </it>using two mutant libraries - one containing transcription factor deletions, and the other containing deletions of DNA repair genes.</p> <p>Results</p> <p>Within the library of transcription factor deletion mutants, we observe significant differences in the sets of genetic interactions identified by the fitness- and sensitivity-based approaches. Notably, among the most likely interactions, only ~50% were identified by both methods. While interactions identified solely by the sensitivity-based approach are modulated in response to drug-induced DNA damage, those identified solely by the fitness-based method remained invariant to the treatment. Comparison of the identified interactions to transcriptional profiles and protein-DNA interaction data indicate that the sensitivity-based method improves the identification of interactions involved in the DNA damage response. Additionally, for the library containing DNA repair mutants, we observe that the sensitivity-based method improves the grouping of functionally related genes, as well as the identification of protein complexes, involved in DNA repair.</p> <p>Conclusion</p> <p>Our results show that the identification of response-modulated genetic interactions can be improved by incorporating the effect of a changing environment directly into the neutrality function marking the absence of epistasis. We expect that this extension of conventional epistatic analysis will facilitate the development of dynamic models of gene networks from quantitative measurements of genetic interactions. While the method was developed for growth phenotype, it should apply equally well for other phenotypes, including the expression of fluorescent reporters.</p
Limit cycles in the presence of convection, a travelling wave analysis
We consider a diffusion model with limit cycle reaction functions, in the
presence of convection. We select a set of functions derived from a realistic
reaction model: the Schnakenberg equations. This resultant form is
unsymmetrical. We find a transformation which maps the irregular equations into
model form. Next we transform the dependent variables into polar form. From
here, a travelling wave analysis is performed on the radial variable. Results
are complex, but we make some simple estimates.
We carry out numerical experiments to test our analysis. An initial `knock'
starts the propagation of pattern. The speed of the travelling wave is not
quite as expected. We investigate further. The system demonstrates distinctly
different behaviour to the left and the right. We explain how this phenomenon
occurs by examining the underlying behaviour.Comment: 20 pages, 5 figure
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