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首页> 外文期刊>The Journal of toxicological sciences >Utilization of a one-dimensional score for surveying chemical-induced changes in expression levels of multiple biomarker gene sets using a large-scale toxicogenomics database.
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Utilization of a one-dimensional score for surveying chemical-induced changes in expression levels of multiple biomarker gene sets using a large-scale toxicogenomics database.

机译：利用一维分数，使用大规模毒理基因组数据库，调查化学诱导的多个生物标记基因集表达水平的变化。

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摘要

A large-scale toxicogenomcis database has now been constructed in the Toxicogenomics Project in Japan (TGP). To facilitate the analytical procedures for such large-scale microarray data, we developed a simple one-dimensional score, named TGP1 which expresses the trend of the changes in expression of biomarker genes as a whole. To evaluate the usefulness of the TGP1 score, microarray data of rat liver and rat hepatocytes deposited in the TGP database were scored for three biomarker gene sets, i.e., carcinogenesis-related, PPARalpha-regulated and glutathione depletion-related gene sets. The TGP1 scoring system gave reasonable results, i.e., the scores for carcinogenesis-related genes were high in omeprazole-, chlorpromazine-, hexachlorobenzene-, sulfasalazine- and Wy-14,643-treated rat livers, that for PPARalpha-regulated genes were high in clofibrate-, Wy-14,643-, gemfibrozil-, benzbromarone- and aspirin-treated rat livers as well as rat hepatocytes, and for glutathione deficiency-related genes were high in omeprazole-, bromobenzene-, acetaminophen- and coumarin-treated rat liver. We concluded that the TGP1 score is useful for surveying the expression changes in multiple biomarker gene sets for a large-scale toxicogenomics database, which would reduce the time of doing conventional multivariate statistical analysis. In addition, the TGP1 score can be applied to screening of compatible biomarker gene sets between rat liver and rat hepatocytes, like PPARalpha-regulated gene sets, which will allow us to develop an appropriate in vitro system for drug safety assessment in vivo.
机译：日本毒物基因组计划（TGP）现在已经建立了大规模的毒理基因组数据库。为了简化此类大规模微阵列数据的分析程序，我们开发了一个简单的一维得分，即TGP1，该得分表达了整个生物标志物基因表达变化的趋势。为了评估TGP1评分的有用性，对三个生物标记基因集（即致癌相关，PPARα调控和谷胱甘肽耗竭相关的基因集）对保存在TGP数据库中的大鼠肝脏和大鼠肝细胞的微阵列数据进行了评分。 TGP1评分系统给出了合理的结果，即在与奥美拉唑，氯丙嗪，六氯苯，柳氮磺胺吡啶和Wy-14643处理的大鼠肝脏中，致癌相关基因的得分较高，而在氯贝酸中，PPARalpha调控的基因得分较高。 -，Wy-14,643-，gembrozil-，benzbromarone和阿司匹林治疗的大鼠肝脏以及大鼠肝细胞，而对于谷胱甘肽缺乏症相关的基因在奥美拉唑，溴苯，对乙酰氨基酚和香豆素治疗的大鼠肝脏中含量较高。我们得出的结论是，TGP1分数可用于调查大规模毒理基因组数据库中多个生物标记基因集的表达变化，这将减少进行常规多元统计分析的时间。此外，TGP1评分可用于筛选大鼠肝脏和大鼠肝细胞之间兼容的生物标志物基因组，例如PPARalpha调节的基因组，这将使我们能够开发合适的体外系统进行体内药物安全性评估。

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