Promoter Prediction Using the Opening Profile of DNA

使用 DNA 开放谱预测启动子

基本信息

批准号：
7053303
负责人：
ANNY A USHEVA-SIMIDJIYSKA
金额：
$ 29.11万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-01 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7053303
关键词：
DNA footprinting DNA replication origin HeLa cells biotechnology complementary DNA computational biology computer simulation eukaryote gene expression profiling genetic library genetic markers genetic promoter element genetic transcription mathematical model method development molecular dynamics nucleic acid quantitation /detection

项目摘要

The field of promoter prediction holds almost limitless potential, but has had very limited success. Instead of analyzing DMA sequence homology, we propose a novel method of eucaryotic promoter prediction based on the physical properties of DNA which arise from the local sequence. Using computer simulations with a nonlinear mathematical model, we predict the localized opening profile of a region of DNA. For several sample eucaryotic promoters, we have demonstrated that the dominant preferential opening positions predicted by the model (and verified by S1 nuclease digestion assays) correlate well with the experimentally-determined transcriptional start sites or major regulatory sites of the gene promoters. We hypothesize that these opening profiles can be applied more generally in seeking out novel gene promoters and transcriptionally significant sites in genomic DNA. Here we propose to further validate the use of nonlinear mathematical models to predict opening profiles as indicators for eukaryotic promoter prediction using known gene core promoters with experimentally-determined transcriptional start sites. We will also seek to apply the computational promoter prediction method in proof-of-concept studies on genes with unidentified promoters and transcriptional start sites. Finally, we plan to develop numerical techniques that allow application of our promoter prediction model on a genomic scale. The simulation-based analysis of DNA opening profiles shows great potential in the prediction of human gene promoters. This method is superior to previous prediction models in that it examines sequence-derived physical properties of DNA rather than sequence homology, however, further investigation is necessary to evaluate and expand the limits of applicability of this method. One of the strongest advantages of the computational model is that it can be used to evaluate opening profiles for any sequence of eukaryotic DNA with very little cost.

启动子预测领域几乎具有无限的潜力，但成功的成功非常有限。我们没有分析DMA序列同源性，而是基于局部序列引起的DNA的物理特性提出了一种新型的桉树启动子预测方法。使用与非线性数学模型的计算机模拟，我们预测了DNA区域的局部开放曲线。对于几个样品嗜酸性启动子，我们已经证明了模型预测的主要优先开放位置（并由S1核酸酶消化分析验证）与实验确定的基因启动子的转录起始位点或主要调节位点。我们假设这一点这些开放曲线可以更普遍地用于寻找新型的基因启动子和基因组DNA中具有转录意义的位点。在这里，我们建议进一步验证非线性数学模型的使用，以预测使用已知的基因核心启动子和实验确定的转录起始位点，以预测真核启动子预测的指标。我们还将寻求将计算启动子预测方法应用于具有未识别启动子和转录起始位点的基因的概念验证研究。最后，我们计划开发数值技术，以允许在基因组规模上应用我们的启动子预测模型。基于模拟的DNA开放曲线分析在人类基因启动子的预测中显示出巨大的潜力。该方法优于先前的预测模型，因为它检查了DNA的序列衍生的物理特性，而不是序列同源性，但是，对于评估和扩大该方法的适用性限制是必要的进一步研究。计算模型最强的优点之一是它可用于评估任何真核DNA序列的开放曲线几乎没有成本。