RESUMO
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 â¼185,000 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.
Assuntos
Regulação Fúngica da Expressão Gênica , Redes Reguladoras de Genes , Modelos Genéticos , Mapeamento de Interação de Proteínas , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Inteligência Artificial , Biologia Computacional , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
As computer systems have become more complex, numerous competing approaches have been proposed for these systems to self-configure, self-manage, self-repair, etc. such that human intervention in their operation can be minimized. In ubiquitous systems, this has always been a central issue as well. In this paper, we overview techniques to implement self-* properties in large-scale, decentralized networks through bio-inspired techniques in general, and gossip-based algorithms in particular. We believe that gossip-based algorithms could be an important inspiration for solving problems in ubiquitous computing as well. As an example, we outline a novel approach to arrange large numbers of mobile agents (e.g. vehicles, rescue teams carrying mobile devices) into different formations in a totally decentralized manner. The approach is inspired by the biological mechanism of cell sorting via differential adhesion, as well as by our earlier work in self-organizing peer-to-peer overlay networks.