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Systems biology approaches to defining transcription regulatory networks in halophilic archaea

机译:定义嗜盐古细菌转录调控网络的系统生物学方法

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摘要

To survive complex and changing environmental conditions, microorganisms use gene regulatory networks (GRNs) composed of interacting regulatory transcription factors (TFs) to control the timing and magnitude of gene expression. Genome-wide datasets; such as transcriptomics and protein-DNA interactions; and experiments such as high throughput growth curves; facilitate the construction of GRNs and provide insight into TF interactions occurring under stress. Systems biology approaches integrate these datasets into models of GRN architecture as well as statistical and/or dynamical models to understand the function of networks occurring in cells. Previously, these types of studies have focused on traditional model organisms (e.g. Escherichia coli, yeast). However, recent advances in archaeal genetics and other tools have enabled a systems approach to understanding GRNs in these relatively less studied archaeal model organisms. In this report, we outline a systems biology workflow for generating and integrating data focusing on the TF regulator. We discuss experimental design, outline the process of data collection, and provide the tools required to produce high confidence regulons for the TFs of interest. We provide a case study as an example of this workflow, describing the construction of a GRN centered on multi-TF coordinate control of gene expression governing the oxidative stress response in the hypersaline-adapted archaeon Halobacterium salinarum. (C) 2015 Elsevier Inc. All rights reserved.
机译:为了在复杂且不断变化的环境条件中生存,微生物使用由相互作用的调控转录因子(TF)组成的基因调控网络(GRN)来控制基因表达的时间和大小。全基因组数据集;例如转录组学和蛋白质-DNA相互作用;和实验,例如高通量增长曲线;促进GRN的构建,并深入了解在压力下发生的TF相互作用。系统生物学方法将这些数据集整合到GRN体系结构模型以及统计和/或动态模型中,以了解细胞中发生的网络的功能。以前,这些类型的研究集中在传统的模式生物(例如大肠杆菌,酵母菌)上。但是,古细菌遗传学和其他工具的最新进展使人们能够采用一种系统的方法来了解这些相对较少研究的古细菌模型生物中的GRN。在本报告中,我们概述了系统生物学工作流程,用于生成和集成以TF调节器为重点的数据。我们讨论了实验设计,概述了数据收集的过程,并提供了为感兴趣的TF生成高置信度规则所需的工具。我们提供了一个案例研究作为该工作流程的示例,描述了以基因表达的多TF坐标控制为中心的GRN的构建,该基因表达控制着高盐适应的古细菌盐沼中的氧化应激反应。 (C)2015 Elsevier Inc.保留所有权利。

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