Disentangling information flow in the Ras-cAMP signaling network
Disentangling information flow in the Ras-cAMP signaling network
复制标题
DOI：
10.1101/gr.4473506
复制
发表时间：
2006-04-01
期刊：
影响因子：
7
通讯作者：
Galitski, T
中科院分区：
文献类型：
--
作者：
Carter, GW;Rupp, S;Galitski, T
信号转导分子的扰动引起的基因组表达效应通常既不局限于一小部分基因，也不是一致的。相反，整个基因组的表达发生了广泛、多样和复杂的变化。这些观察表明，信号转导不是通过孤立的信息流路径传递到基因组中不同的基因组。相反，信息流的多条纠缠路径会影响重叠的基因集。以酿酒酵母中的Ras-cAMP途径为模型系统，我们对关键途径元件进行了扰动，并收集了基因组表达数据。奇异值分解被用来将全基因组的转录反应分离成重叠的基因组所表现出的加权表达成分。分子相互作用数据被整合起来，将基因群与受干扰的信号元件联系起来。由此产生的一系列链接的子网络映射了通过密集信号网络的多条假定的信息流路径，并为整个基因组的复杂基因表达效应提供了一套可验证的假设。
The perturbation of signal-transduction molecules elicits genomic-expression effects that are typically neither restricted to a small set of genes nor uniform. Instead there are broad, varied, and complex changes in expression across the genome. These observations suggest that signal transduction is not mediated by isolated pathways of information flow to distinct groups of genes in the genome. Rather, multiple entangled paths of information flow influence overlapping sets of genes. Using the Ras-cAMP pathway in Saccharomyces cerevisiae as a model system, we perturbed key pathway elements and collected genomic-expression data. Singular value decomposition was applied to separate the genome-wide transcriptional response into weighted expression components exhibited by overlapping groups of genes. Molecular interaction data were integrated to connect gene groups to perturbed signaling elements. The resulting series of linked subnetworks maps multiple putative pathways of information flow through a dense signaling network, and provides a set of testable hypotheses for complex gene-expression effects across the genome.