Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data.
Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data.
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DOI：
10.1093/nar/gkq149
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发表时间：
2010-06
影响因子：
14.9
通讯作者：
Demoulin JB
中科院分区：
文献类型：
--
作者：
Essaghir A;Toffalini F;Knoops L;Kallin A;van Helden J;Demoulin JB
从微阵列数据中破译转录因子网络仍然很困难。本研究提出了一种简单的方法来推断转录因子的调控从微阵列数据基于良好表征的靶基因。我们生成了一个包含与2720个靶基因和6401个实验验证的调控相关的转录因子的目录。当它是可用的，转录激活和抑制之间的区别包括每个调节。接下来，我们构建了一个工具（www.tfacts.org），将提交的基因列表与目录中的目标基因进行比较，以检测受调节的转录因子。TFactS通过各种模型中已发表的调控基因列表进行验证，并与基于计算机启动子分析的工具进行比较。接下来，我们分析了NCI60癌症微阵列数据集，并显示了SOX10、MITF和JUN在黑色素瘤中的调控作用。然后，我们进行了微阵列实验，比较了不同生长因子刺激下人成纤维细胞的基因表达反应。TFactS预测了PDGF-BB对信号转导因子和转录因子激活因子的特异性激活，实验证实了这一点。我们的研究结果表明，转录因子靶基因的表达水平构成了转录因子调控的稳健标志，可以有效地用于微阵列数据挖掘。
Deciphering transcription factor networks from microarray data remains difficult. This study presents a simple method to infer the regulation of transcription factors from microarray data based on well-characterized target genes. We generated a catalog containing transcription factors associated with 2720 target genes and 6401 experimentally validated regulations. When it was available, a distinction between transcriptional activation and inhibition was included for each regulation. Next, we built a tool (www.tfacts.org) that compares submitted gene lists with target genes in the catalog to detect regulated transcription factors. TFactS was validated with published lists of regulated genes in various models and compared to tools based on in silico promoter analysis. We next analyzed the NCI60 cancer microarray data set and showed the regulation of SOX10, MITF and JUN in melanomas. We then performed microarray experiments comparing gene expression response of human fibroblasts stimulated by different growth factors. TFactS predicted the specific activation of Signal transducer and activator of transcription factors by PDGF-BB, which was confirmed experimentally. Our results show that the expression levels of transcription factor target genes constitute a robust signature for transcription factor regulation, and can be efficiently used for microarray data mining.
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作者：
Defrance M;Touzet H
通讯作者：
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影响因子：
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影响因子：
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作者：
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