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Detecting subnetwork-level dynamic correlations

机译:检测子网级动态关联

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摘要

>Motivation: The biological regulatory system is highly dynamic. The correlations between many functionally related genes change over different biological conditions. Finding dynamic relations on the existing biological network may reveal important regulatory mechanisms. Currently no method is available to detect subnetwork-level dynamic correlations systematically on the genome-scale network. Two major issues hampered the development. The first is gene expression profiling data usually do not contain time course measurements to facilitate the analysis of dynamic relations, which can be partially addressed by using certain genes as indicators of biological conditions. Secondly, it is unclear how to effectively delineate subnetworks, and define dynamic relations between them.>Results: Here we propose a new method named LANDD (Liquid Association for Network Dynamics Detection) to find subnetworks that show substantial dynamic correlations, as defined by subnetwork A is concentrated with Liquid Association scouting genes for subnetwork B. The method produces easily interpretable results because of its focus on subnetworks that tend to comprise functionally related genes. Also, the collective behaviour of genes in a subnetwork is a much more reliable indicator of underlying biological conditions compared to using single genes as indicators. We conducted extensive simulations to validate the method’s ability to detect subnetwork-level dynamic correlations. Using a real gene expression dataset and the human protein-protein interaction network, we demonstrate the method links subnetworks of distinct biological processes, with both confirmed relations and plausible new functional implications. We also found signal transduction pathways tend to show extensive dynamic relations with other functional groups.>Availability and Implementation: The R package is available at .>Contacts: , or >Supplementary information: are available at Bioinformatics online.
机译:>动机:生物调节系统是高度动态的。许多功能相关基因之间的相关性随不同的生物学条件而变化。在现有生物网络上发现动态关系可能会揭示重要的调控机制。当前,尚无方法可以在基因组规模的网络上系统地检测子网级动态相关性。有两个主要问题阻碍了这一发展。首先是基因表达谱数据通常不包含时程测量值以促进动态关系分析,这可以通过使用某些基因作为生物状况指标来部分解决。其次,尚不清楚如何有效地描绘子网并定义它们之间的动态关系。>结果:在这里,我们提出了一种名为LANDD(网络动态检测液体协会)的新方法来查找表现出实质性动态的子网。子网络A定义的相关性集中于子网络B的Liquid Association筛选基因。该方法产生易于解释的结果,因为它关注的是倾向于包含功能相关基因的子网络。而且,与使用单个基因作为指标相比,子网中基因的集体行为是潜在生物学状况的更可靠指标。我们进行了广泛的仿真,以验证该方法检测子网级动态关联的能力。使用真实的基因表达数据集和人类蛋白质-蛋白质相互作用网络,我们证明了该方法链接了不同生物学过程的子网络,具有确定的关系和可能的新功能含义。我们还发现信号转导途径倾向于显示与其他功能组的广泛动态关系。>可用性和实现:R包可从。>联系人:或> Supplementary获得信息:可从生物信息学在线获得。

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