基于数据挖掘和网络分析的环丙沙星诱导铜绿假单胞菌PAO1基因表达动态和Lexa功能丧失

J. Molina-Mora, Rebeca Campos-Sánchez, Fernando Quiles García
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引用次数: 4

摘要

铜绿假单胞菌是一种机会性病原体,可引起人类多种感染,并经常产生对抗生素的耐药机制,这使得其治疗困难。在这项研究中,我们使用数据挖掘技术和网络分析应用基因表达分析来评估暴露于环丙沙星的时间效应,以及由细胞应激下SOS反应的调节因子LexA功能丧失引起的变化。最初,使用聚类算法的全局差异表达谱表明抗生素暴露的影响主要由时间决定,而不是由LexA功能的丧失决定。这一点通过在不同条件下进行属性选择和差异表达分析得到了验证,其中菌株之间的最大差异不到3.3%,但随着时间的推移,差异高达21%。与网络分析一起,在评估时间变化时确定了拓扑指标的显着增加。功能注释显示代谢途径随着时间的推移而丰富,但在比较菌株时却没有。总的来说,研究结果表明,随着时间的推移,对环丙沙星的反应往往会加剧,而在LexA活性功能丧失的情况下,环丙沙星的反应保持稳定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gene Expression Dynamics Induced by Ciprofloxacin and Loss of Lexa Function in Pseudomonas Aeruginosa PAO1 Using Data Mining and Network Analysis
Pseudomonas aeruginosa is an opportunistic pathogen that causes a variety of infections in humans and frequently develops mechanisms of resistance to antibiotics, which makes its treatment difficult. In this study we applied gene expression analysis using data mining techniques and network analysis to evaluate the temporal effects of exposure to ciprofloxacin and the changes caused by the loss of function of LexA, a regulator of the SOS response to the cellular stress. Initially, global differential expression profiles using clustering algorithms suggested that the effects of antibiotic exposure were determined primarily by time and not by loss of LexA function. This was verified by performing attribute selection and differential expression analysis among conditions, where less than 3.3% of maximum difference between strains but up to 21% of differences were observed over time. Together with network analysis, a significant increase in topological metrics was determined when evaluating temporal changes. Functional annotation showed metabolic pathways enriched over time but not when comparing strains. Overall, the results obtained revealed that the response to ciprofloxacin tends to be exacerbated over time and that it remains stable in the face of the loss of function of LexA activity.
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