Guziolowski Carito, Bourdé Annabel, Moreews Francois, Siegel Anne
INRIA, Centre Rennes - Bretagne Atlantique, Symbiose, Campus de Beaulieu, 35042 Rennes, France.
BMC Genomics. 2009 May 26;10:244. doi: 10.1186/1471-2164-10-244.
The method most commonly used to analyse regulatory networks is the in silico simulation of fluctuations in network components when a network is perturbed. Nevertheless, confronting experimental data with a regulatory network entails many difficulties, such as the incomplete state-of-art of regulatory knowledge, the large-scale of regulatory models, heterogeneity in the available data and the sometimes violated assumption that mRNA expression is correlated to protein activity.
We have developed a plugin for the Cytoscape environment, designed to facilitate automatic reasoning on regulatory networks. The BioQuali plugin enhances user-friendly conversions of regulatory networks (including reference databases) into signed directed graphs. BioQuali performs automatic global reasoning in order to decide which products in the network need to be up or down regulated (active or inactive) to globally explain experimental data. It highlights incomplete regions in the network, meaning that gene expression levels do not globally correlate with existing knowledge on regulation carried by the topology of the network.
The BioQuali plugin facilitates in silico exploration of large-scale regulatory networks by combining the user-friendly tools of the Cytoscape environment with high-performance automatic reasoning algorithms. As a main feature, the plugin guides further investigation regarding a system by highlighting regions in the network that are not accurately described and merit specific study.
分析调控网络最常用的方法是对网络受到扰动时网络组件的波动进行计算机模拟。然而,将实验数据与调控网络进行对比存在诸多困难,比如调控知识的现状不完整、调控模型规模庞大、可用数据存在异质性,以及有时mRNA表达与蛋白质活性相关这一假设不成立。
我们为Cytoscape环境开发了一个插件,旨在促进对调控网络的自动推理。BioQuali插件增强了调控网络(包括参考数据库)到带符号有向图的用户友好型转换。BioQuali进行自动全局推理,以确定网络中的哪些产物需要上调或下调(激活或失活),从而全局解释实验数据。它突出显示网络中不完整的区域,这意味着基因表达水平与网络拓扑结构所承载的现有调控知识在全局上不相关。
BioQuali插件通过将Cytoscape环境的用户友好型工具与高性能自动推理算法相结合,促进了对大规模调控网络的计算机探索。作为一个主要特点,该插件通过突出显示网络中描述不准确且值得具体研究的区域,引导对系统进行进一步研究。