将过度表达的上游基序与基因表达相关联：真核生物调控元件发现的计算方法
Correlating overrepresented upstream motifs to gene expression: a computational approach to regulatory element discovery in eukaryotes
摘要：
真核生物中的基因调控主要通过转录因子与通常位于编码区上游的相当短的识别基序结合来实现。我们提出了一种新的计算方法来确定在真核基因的上游区域的调控元件。这些基因被分组在集合中，在它们的上游序列中共享一个过度表达的短基序。对于每个集合，确定来自微阵列实验的平均表达水平：如果该水平显著高于或低于整个基因组的平均水平，则集合中基因共享的过度表达基序可能在其调节中发挥作用。该方法进行了测试，通过将其应用到酿酒酵母的基因组，使用公开的结果的DNA微阵列实验，其中几乎所有的基因的表达水平进行了测量期间的二次发酵转换到呼吸。正确鉴定了几个已知的基序，并确定了一个新的候选调控序列。
英文摘要：
Gene regulation in eukaryotes is mainly effected through transcription factors binding to rather short recognition motifs generally located upstream of the coding region. We present a novel computational method to identify regulatory elements in the upstream region of eukaryotic genes. The genes are grouped in sets sharing an overrepresented short motif in their upstream sequence. For each set, the average expression level from a microarray experiment is determined: If this level is significantly higher or lower than the average taken over the whole genome, then the overerpresented motif shared by the genes in the set is likely to play a role in their regulation. The method was tested by applying it to the genome of Saccharomyces cerevisiae, using the publicly available results of a DNA microarray experiment, in which expression levels for virtually all the genes were measured during the diauxic shift from fermentation to respiration. Several known motifs were correctly identified, and a new candidate regulatory sequence was determined.
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