Structure of genomic DNA at single-nucleotide resolution

本申请描述了一个旨在回答以下问题的项目：人类基因组的某些部分是否通过其结构而不是直接通过其核苷酸序列发挥功能？为了解决这个问题，基于DNA的羟基自由基切割模式，在单核苷酸分辨率下绘制了人类基因组DNA的30 Mb ENCODE区域的结构图。建立了一个免费的数据库ORChID （OH Radical Cleavage Intensity database）来存储羟基自由基裂解数据。开发了一种算法来预测任何DNA序列的羟基自由基切割模式，以达到高精度。将该算法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结构数据集可以搜索基因组DNA中可能与生物学功能相关的结构模式。该项目的第一个目标是开发高通量的方法来收集羟基自由基裂解数据，以提高兰花数据库的预测能力。第二个目标是定位人类基因组DNA中处于选择性进化压力下的结构特征，但其确切的核苷酸序列没有经过选择。在应用程序中详细介绍了实验数据产生和信息学管道，数据验证和验证协议以及数据沉积计划。

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.