Sources of variation in baseline gene expression levels from toxicogenomics study control animals across multiple laboratories.
Sources of variation in baseline gene expression levels from toxicogenomics study control animals across multiple laboratories.
复制标题
来自毒理基因组学研究基因基因表达水平的变化来源研究动物跨多个实验室。
DOI：
10.1186/1471-2164-9-285
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发表时间：
2008-06-12
期刊：
影响因子：
4.4
通讯作者：
Thompson KL
中科院分区：
文献类型：
--
作者：
Boedigheimer MJ;Wolfinger RD;Bass MB;Bushel PR;Chou JW;Cooper M;Corton JC;Fostel J;Hester S;Lee JS;Liu F;Liu J;Qian HR;Quackenbush J;Pettit S;Thompson KL
通过更好地描述个体、环境和技术因素引起的差异，将加强基因表达谱在临床和实验室环境中的使用。在毒素基因组学研究的对照部门内，对未经处理或使用载体处理的动物的微阵列数据进行荟萃分析，可以产生关于基因表达基线波动的有用信息，尽管对照动物的数据尚未大规模获得，也没有最适合数据挖掘的形式。健康与环境科学研究所基因组学在基于机制的风险评估中的应用技术委员会的一个工作组收集了对照动物微阵列表达数据的数据集，以便为评估基线基因表达的变异性提供公共资源。来自16个不同机构的500多个来自对照大鼠肝和肾的Affymetrix芯片的数据被收集。每只动物获得了35个生物和技术因素，描述了广泛的研究特征，并使用多变量统计和图形技术详细评估了其中一个子集对总变异性的贡献。作为变异性的关键来源出现的研究因素包括性别、器官切片、压力和禁食状态。这些和其他研究因素被确定为关键描述符，应包括在由独立来源解释结果所需的关于毒素基因组学研究的最低信息中。变异最大和变化最小的、性别选择性的或因禁食而改变的基因也被识别并进行了功能分类。更好地表征对照动物的基因表达变异性将有助于毒理基因组学研究的设计和对其结果的解释。
The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies could yield useful information on baseline fluctuations in gene expression, although control animal data has not been available on a scale and in a form best served for data-mining. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selective, or altered by fasting were also identified and functionally categorized. Better characterization of gene expression variability in control animals will aid in the design of toxicogenomics studies and in the interpretation of their results.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
2
作者：
Tamura, Kotaro;Ono, Atsushi;Urushidani, Tetsuro
通讯作者：
Urushidani, Tetsuro
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP
影响因子：
4.6
作者：
Bauer, M;Hamm, AC;Katzenberger, JD
通讯作者：
Katzenberger, JD
影响因子：
--
作者：
Stahlberg, Nina;Merino, Roxana;Flores-Morales, Amilcar
通讯作者：
Flores-Morales, Amilcar