Structure of genomic DNA at single-nucleotide resolution

这个应用程序描述了一个项目，旨在回答这个问题，人类基因组的某些部分功能是通过它们的结构，而不是直接通过它们的核苷酸序列？为了解决这个问题，基于DNA的羟基自由基切割模式，已经产生了单核苷酸分辨率的人基因组DNA的30 Mb的ENCODE区域的结构图。构建了一个免费可用的数据库ORChID（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，并将所得数据存储在UCSC基因组浏览器中。可以搜索DNA结构数据的该数据集以寻找可能与生物功能相关的基因组DNA中的结构模式。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ORChID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性进化压力下，但确切的核苷酸序列并没有受到选择。实验数据生产和信息学管道，数据验证和确认协议，以及数据存储计划在应用程序中有详细说明。

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.