Pham Tho Hoan, Satou Kenji, Ho Tu Bao
Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Tatsunokuchi, Ishikawa 923-1292, Japan.
Genome Inform. 2004;15(2):287-95.
In eukaryotes, gene expression is controlled by various transcription factors that bind to the promoter regions. Transcription factors may act positively, negatively or not at all. Different combinations of them may also activate or repress gene expression, and form regulatory networks of transcription. Uncovering such regulatory networks is a central challenge in genomic biology. In this study, we first defined a new kind of motifs in regulatory networks, transcriptional regulatory modules (TRMs), with the form factorset --> geneset, which emphasizes the combinatorial gene control of the group of factors factorset on the group of genes geneset. Second, we developed an efficient method based on a closed itemset mining technique for finding the two most informative kinds of TRMs, closed inf-TRMs and closed sup-TRMs, from factor DNA-binding sites and gene expression profiles data. The set of all closed inf-TRMs and closed sup-TRMs is often orders of magnitude smaller than the set of all TRMs but does not loss any information. When being applied to yeast data, our method produced results that are more compact, concise and comprehensive than those from previous studies to identify and interpret the transcriptional role of regulator combinations on sets of genes.
Supplementary files: http://www.jaist.ac.jp/~h-pham/regulation/.
在真核生物中,基因表达受多种与启动子区域结合的转录因子控制。转录因子可能起正向、负向作用,也可能不起任何作用。它们的不同组合还可能激活或抑制基因表达,从而形成转录调控网络。揭示此类调控网络是基因组生物学中的一项核心挑战。在本研究中,我们首先在调控网络中定义了一种新的基序,即转录调控模块(TRM),其形式为因子集 --> 基因集,它强调了因子集对基因集的组合基因控制。其次,我们基于封闭项集挖掘技术开发了一种高效方法,用于从因子DNA结合位点和基因表达谱数据中找到两种最具信息性的TRM,即封闭信息TRM和封闭支持TRM。所有封闭信息TRM和封闭支持TRM的集合通常比所有TRM的集合小几个数量级,但不会丢失任何信息。当应用于酵母数据时,我们的方法产生的结果比以往研究更紧凑、简洁且全面,能够识别和解释调控因子组合对基因集的转录作用。