CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai Institutes for Biological Sciences, 320 Yue Yang Road, 200031, Shanghai, China.
BMC Bioinformatics. 2010 May 20;11:267. doi: 10.1186/1471-2105-11-267.
Observed co-expression of a group of genes is frequently attributed to co-regulation by shared transcription factors. This assumption has led to the hypothesis that promoters of co-expressed genes should share common regulatory motifs, which forms the basis for numerous computational tools that search for these motifs. While frequently explored for yeast, the validity of the underlying hypothesis has not been assessed systematically in mammals. This demonstrates the need for a systematic and quantitative evaluation to what degree co-expressed genes share over-represented motifs for mammals.
We identified 33 experiments for human and mouse in the ArrayExpress Database where transcription factors were manipulated and which exhibited a significant number of differentially expressed genes. We checked for over-representation of transcription factor binding sites in up- or down-regulated genes using the over-representation analysis tool oPOSSUM. In 25 out of 33 experiments, this procedure identified the binding matrices of the affected transcription factors. We also carried out de novo prediction of regulatory motifs shared by differentially expressed genes. Again, the detected motifs shared significant similarity with the matrices of the affected transcription factors.
Our results support the claim that functional regulatory motifs are over-represented in sets of differentially expressed genes and that they can be detected with computational methods.
观察到一组基因的共表达通常归因于共同转录因子的共调控。这一假设导致了这样的假设：共表达基因的启动子应该共享共同的调节基序，这是许多用于搜索这些基序的计算工具的基础。虽然在酵母中经常被探索，但该假设的有效性在哺乳动物中尚未得到系统评估。这表明需要对哺乳动物共表达基因共享过度表达基序的程度进行系统和定量评估。
我们在 ArrayExpress 数据库中确定了 33 项人类和小鼠的实验，其中转录因子被操纵，并显示出大量差异表达的基因。我们使用过度表达分析工具 oPOSSUM 检查上调或下调基因中转录因子结合位点的过度表达。在 33 项实验中的 25 项中，该程序确定了受影响转录因子的结合矩阵。我们还进行了差异表达基因共享调控基序的从头预测。同样，检测到的基序与受影响转录因子的矩阵具有显著的相似性。
我们的结果支持这样的观点，即功能调节基序在差异表达基因集中过度表达，可以通过计算方法检测到。
