Structure of genomic DNA at single-nucleotide resolution

这项申请描述了一个旨在回答这个问题的项目，人类基因组的某些部分是通过它们的结构而不是直接通过它们的核苷酸序列发挥功能的？为了解决这个问题，根据DNA的羟基自由基裂解模式，制作了单核苷酸分辨率下人类基因组DNA编码区30Mb的结构图。建立了一个免费可用的数据库，兰花(OH自由基裂解强度数据库)，以存储羟基自由基裂解数据。开发了一种算法，可以高精度地预测任意DNA序列的羟基自由基裂解模式。该算法被应用于人类基因组的ENCODE区域，并将结果数据存储在UCSC基因组浏览器中。这个DNA结构数据集可以在基因组DNA中搜索可能与生物功能相关的结构模式。该项目的第一个目标是开发收集羟基自由基裂解数据的高通量方法，以增强兰花数据库的预测能力。第二个目标是定位人类基因组DNA中的结构特征，这些结构特征处于选择进化的压力下，但其确切的核苷酸序列尚未被选择。申请中详细介绍了实验数据生产和信息学管道、数据验证和确认协议以及数据存储计划。

This application describes a project that aims to answer the question, do some parts of the human genome function by virtue of their structure, and not directly by their nucleotide sequence? To address this question a structural map of the 30 Mb of the ENCODE regions of human genomic DNA, at single-nucleotide resolution, has been produced, based on hydroxyl radical cleavage patterns of DNA. A freely available database, ORChID (OH Radical Cleavage Intensity Database), was constructed to house hydroxyl radical cleavage data. An algorithm was developed to predict the hydroxyl radical cleavage pattern of any DNA sequence to high accuracy. This algorithm was applied to the ENCODE regions of the human genome, and the resulting data were deposited in the UCSC genome browser. This dataset of DNA structural data can be searched for structural patterns in genomic DNA that may be associated with biological function. The first objective of this project is to develop high-throughput methods for collecting hydroxyl radical cleavage data, to enhance the predictive power of the ORChID database. The second objective is to locate structural features in human genomic DNA that are under selective evolutionary pressure, but for which the exact nucleotide sequence is not under selection. Experimental data production and informatics pipelines, data verification and validation protocols, and plans for data deposition are detailed in the application.