Finding motifs in promoter regions
Finding motifs in promoter regions
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DOI：
10.1089/cmb.2005.12.314
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发表时间：
2005-04-01
影响因子：
1.7
通讯作者：
Domany, E
中科院分区：
文献类型：
--
作者：
Hertzberg, L;Zuk, O;Domany, E
分子生物学的一个中心问题是理解控制基因表达的调节机制。全基因组序列的可用性为计算方法寻找转录调控中的关键元件开辟了道路。这些包括用于发现DNA结合蛋白（如转录因子）的结合位点的方法。转录因子结合位点的常见表示是位置特异性得分矩阵（PSSM）。我们开发了一种概率的方法来寻找假定的结合位点。给定启动子序列和PSSM，我们扫描启动子并找到具有最大得分的位置。然后我们计算在随机启动子上获得如此最大或更高分数的概率。这是推定结合位点的p值。以这种方式，我们在酿酒酵母的上游序列中搜索推定的结合位点，其中一些结合位点是已知的（根据酿酒酵母启动子数据库，SCPD）。我们的方法产生精确的p值，或者比其他方法更好的估计，这改善了搜索的结果。对于每一个基因，我们发现其统计上显着的推定结合位点。通过与已知结合位点的比较，我们测量了真阳性率，并且还将我们的结果与MatInspector的结果进行了比较，MatInspector是一种商业上可获得的软件，其根据PSSM在DNA序列中寻找推定的结合位点。我们的结果明显更好。与我们相比，MatInspector并不计算其结果的确切统计显著性。
A central issue in molecular biology is understanding the regulatory mechanisms that control gene expression. The availability of whole genome sequences opens the way for computational methods to search for the key elements in transcription regulation. These include methods for discovering the binding sites of DNA-binding proteins, such as transcription factors. A common representation of transcription factor binding sites is a position specific score matrix (PSSM). We developed a probabilistic approach for searching for putative binding sites. Given a promoter sequence and a PSSM, we scan the promoter and find the position with the maximal score. Then we calculate the probability to get such a maximal score or higher on a random promoter. This is the p-value of the putative binding site. In this way, we searched for putative binding sites in the upstream sequences of Saccharomyces cerevisiae, where some binding sites are known ( according to the Saccharomyces cerevisiae Promoters Database, SCPD). Our method produces either exact p-values, or a better estimate for them than other methods, and this improves the results of the search. For each gene we found its statistically significant putative binding sites. We measured the rates of true positives, by a comparison to the known binding sites, and also compared our results to these of MatInspector, a commercially available software that looks for putative binding sites in DNA sequences according to PSSMs. Our results were significantly better. In contrast with us, MatInspector doesn't calculate the exact statistical significance of its results.