Park Peter J, Butte Atul J, Kohane Isaac S
Informatics Program and Division of Endocrinology, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
Bioinformatics. 2002 Dec;18(12):1576-84. doi: 10.1093/bioinformatics/18.12.1576.
Gene regulatory elements are often predicted by seeking common sequences in the promoter regions of genes that are clustered together based on their expression profiles. We consider the problem in the opposite direction: we seek to find the genes that have similar promoter regions and determine the extent to which these genes have similar expression profiles.
We use the data sets from experiments on Saccharomyces cerevisiae. Our similarity measure for the promoter regions is based on the set of common mapped or putative transcription factor binding sites and other regulatory elements in the upstream region of the genes, as contained in the Saccharomyces cerevisiae Promoter Database. We pair up the genes with high similarity scores and compare their expression levels in time-course experiment data. We find that genes with similar promoter regions on the average have significantly higher correlation, but it can vary widely depending on the genes. This confirms that the presence of similar regulatory elements often does not correspond to similarity in expression profiles and indicates that finding transcription factor binding sites or other regulatory elements starting with the expression patterns may be limited in many cases. Regardless of the correlation, the degree to which the profiles agree under different experimental conditions can be examined to derive hypotheses concerning the role of common regulatory elements. Overall, we find that considering the relationship between the promoter regions and the expression profiles starting with the regulatory elements is a difficult but useful process that can provide valuable insights.
基因调控元件通常是通过在基于表达谱聚类在一起的基因的启动子区域中寻找共同序列来预测的。我们从相反的方向考虑这个问题：我们试图找到具有相似启动子区域的基因，并确定这些基因在多大程度上具有相似的表达谱。
我们使用了来自酿酒酵母实验的数据集。我们对启动子区域的相似性度量基于酿酒酵母启动子数据库中基因上游区域的共同映射或推定的转录因子结合位点以及其他调控元件的集合。我们将具有高相似性得分的基因配对，并在时间进程实验数据中比较它们的表达水平。我们发现，平均而言，具有相似启动子区域的基因具有显著更高的相关性，但这可能因基因而异。这证实了相似调控元件的存在通常并不对应于表达谱的相似性，并表明在许多情况下，从表达模式出发寻找转录因子结合位点或其他调控元件可能是有限的。无论相关性如何，都可以检查在不同实验条件下谱图的一致程度，以得出关于共同调控元件作用的假设。总体而言，我们发现从调控元件出发考虑启动子区域与表达谱之间的关系是一个困难但有用的过程，它可以提供有价值的见解。
