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利用自组织映射从DNA微阵列数据中提取酿酒酵母盐渗透耐受性的隐藏特征:氨基酸的生物合成

Extracting the hidden features in saline osmotic tolerance in Saccharomyces cerevisiae from DNA microarray data using the self-organizing map: biosynthesis of amino acids.

作者信息

Pandey Gaurav, Yoshikawa Katsunori, Hirasawa Takashi, Nagahisa Keisuke, Katakura Yoshio, Furusawa Chikara, Shimizu Hiroshi, Shioya Suteaki

机构信息

Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.

出版信息

Appl Microbiol Biotechnol. 2007 May;75(2):415-26. doi: 10.1007/s00253-007-0837-8. Epub 2007 Jan 30.

Abstract

During saline stress, Saccharomyces cerevisiae changes its metabolic fluxes through the direct accumulation of metabolites such as glycerol and trehalose, which in turn provide tolerance to the cell against stress. Previous research shows that the various controls at both transcriptional and translational levels decide the phenomenon of stress, but details about such transition is still not very clear. This paper attempts to extract some hidden features through the information extraction approach from DNA microarray data during transition to osmotic tolerance, which are expected to be important in directing to the tolerance stage upon encountering osmotic stress in yeast. Time course of DNA microarray data during osmotic tolerance was analyzed by computational approach 'self-organizing map (SOM) extended with hierarchical clustering'. Since eukaryotic gene expression is governed by short regulatory sequences found upstream in promoter regions, therefore clusters containing the similar profiles obtained by SOM were further analyzed for overrepresentation of known regulatory binding sites in promoter region. It was found that apart from known and expected 'STRE' during osmotic stress, the 'GCN4' binding site is also found to be significant. Hence, it was suggested that the process of osmotic tolerance proceeds through a stage of amino acid starvation. The intracellular amino acids pool also found to be depleted during transition and restoration is faster in brewing strain than laboratory strain. Experiments involving supplementation of amino acids helps in reducing the lag time for recovery, which was found to be similar to that of brewing strain.

摘要

在盐胁迫期间,酿酒酵母通过直接积累甘油和海藻糖等代谢物来改变其代谢通量,这些代谢物进而为细胞提供抗胁迫能力。先前的研究表明,转录和翻译水平上的各种调控决定了胁迫现象,但这种转变的细节仍不是很清楚。本文试图通过信息提取方法从DNA微阵列数据中提取一些隐藏特征,这些特征在指导酵母遇到渗透胁迫时进入耐受阶段方面有望发挥重要作用。采用“扩展了层次聚类的自组织映射(SOM)”这一计算方法分析了渗透耐受期间DNA微阵列数据的时间进程。由于真核基因表达受启动子区域上游发现的短调控序列控制,因此对通过SOM获得的具有相似图谱的聚类进一步分析其启动子区域中已知调控结合位点的过度富集情况。结果发现,除了渗透胁迫期间已知和预期的“应激反应元件(STRE)”外,还发现“GCN4”结合位点具有显著性。因此,有人提出渗透耐受过程会经历一个氨基酸饥饿阶段。在转变过程中还发现细胞内氨基酸池会耗尽,并且酿造菌株的恢复速度比实验室菌株更快。涉及补充氨基酸的实验有助于减少恢复的延迟时间,发现其与酿造菌株的延迟时间相似。

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