Exploring drug action on Mycobacterium tuberculosis using affymetrix oligonucleotide genechips
Exploring drug action on Mycobacterium tuberculosis using affymetrix oligonucleotide genechips
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DOI：
10.1016/j.tube.2005.07.004
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发表时间：
2006-03-01
期刊：
影响因子：
3.2
通讯作者：
Fu, LM
中科院分区：
文献类型：
--
作者：
Fu, LM
DNA微阵列已迅速成为结核分枝杆菌研究的重要工具。白色微阵列方法产生了有价值的信息，最近的一项调查发现，在相关问题上，不同实验室产生的微阵列数据之间缺乏相关性，这引起了人们对研究结果可信度的担忧。Affytek寡核苷酸阵列已被证明比其他平台更可靠地询问基因表达的变化。然而，这种类型的阵列系统尚未应用于M.结核本研究旨在探索Affyphidae芯片系统在监测药物诱导的M.结核病，与其他相关研究进行比较，并进行跨平台分析。全基因组基因表达谱的M。使用Affymba阵列系统获得了对包括INH（异烟肼）和乙硫异烟胺的药物治疗有反应的结核病患者。通过生物信息学分析来自RNA样品和基因探针杂交的微阵列数据来鉴定上调或下调的基因。我们的方法基于Affyssin系统，鉴定了所有在原始参考文献中报道的药物诱导基因以及一些以前在相同药物处理下未被识别的其他基因。例如，Affyphase系统揭示了在给定浓度水平下，INH和乙硫异烟胺都诱导Rv2524c（fas），如大多数实施该基因序列的探针组所表明的。这一发现与以前的观察结果相矛盾，即Fas的表达不受INH治疗的影响。该实施例说明了某些基因的表达变化的测定是探针依赖性的，并且多个探针组表示的适当使用是Affyphase系统的优点。我们的数据还表明，尽管上调的基因表达模式反映了药物的作用模式，但下调的模式在很大程度上是非特异性的。根据我们的分析，Affyphase芯片系统是一个可靠的工具，用于研究药物基因组学M。结核病，并在抗结核药物的研究和开发中发挥了良好作用。(C)2005爱思唯尔有限公司保留所有权利。
DNA microarrays have rapidly emerged as an important tool for Mycobacterium tuberculosis research. White the microarray approach has generated valuable information, a recent survey has found a lack of correlation among the microarray data produced by different laboratories on related issues, raising a concern about the credibility of research findings. The Affymetrix oligonucleotide array has been shown to be more reliable for interrogating changes in gene expression than other platforms. However, this type of array system has not been applied to the pharmacogenomic study of M. tuberculosis. The goat here was to explore the strength of the Affymetrix array system for monitoring drug-induced gene expression in M. tuberculosis, compare with other related studies, and conduct cross-platform analysis. The genome-wide gene expression profiles of M. tuberculosis in response to drug treatments including INH (isoniazid) and ethionamide were obtained using the Affymetrix array system. Up-regulated or down-regulated genes were identified through bioinformatic analysis of the microarray data derived from the hybridization of RNA samples and gene probes. Based on the Affymetrix system, our method identified all drug-induced genes reported in the original reference work as well as some other genes that have not been recognized previously under the same drug treatment. For instance, the Affymetrix system revealed that Rv2524c (fas) was induced by both INH and ethionamide under the given levels of concentration, as suggested by most of the probe sets implementing this gene sequence. This finding is contradictory to previous observations that the expression of fas is not changed by INH treatment. This example illustrates that the determination of expression change for certain genes is probe-dependent, and the appropriate use of multiple probe-set representation is an advantage with the Affymetrix system. Our data also suggest that whereas the up-regulated gene expression pattern reflects the drug's mode of action, the down-regulated pattern is largely non-specific. According to our analysis, the Affymetrix array system is a reliable tool for studying the pharmacogenomics of M. tuberculosis and lends itself well in the research and development of anti-TB drugs. (C) 2005 Elsevier Ltd. All rights reserved.