Novel approaches to map DNA replication traffic in a genome-wide scale

在全基因组范围内绘制 DNA 复制流量图的新方法

基本信息

批准号：
9923689
负责人：
Dieter Meinrad Egli
金额：
$ 20.53万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9923689
关键词：
ATAC-seq Address Affect Aging Asians Bioinformatics Biological Phenomena Biological Process Bromodeoxyuridine Cell Proliferation Cells Cellular biology ChIP-seq Communities Computer software Computing Methodologies Cultured Cells Custom DNA DNA Markers DNA Modification Process DNA Replication Timing DNA Sequence DNA analysis DNA biosynthesis DNA replication fork DNA sequencing DNA-Directed DNA Polymerase Data Detection Development Disease Drops Family Genetic Genome Genomics Goals Human Human Genome Immunoprecipitation Knowledge Link Location Malignant Neoplasms Maps Measures Methodology Methods Modeling Modification Names Nucleotides Optics Pattern Phase Physiologic pulse Positioning Attribute Price Protocols documentation Publishing Replication Initiation Reproducibility Resolution Resources Series Signal Transduction Technology Testing Time Tissues base cell type computational pipelines cost effective deep neural network electrical property epigenomics experience genome integrity genome-wide genome-wide analysis insertion/deletion mutation insight nanopore new technology novel novel strategies nucleotide analog sequencing platform single molecule stem cell differentiation tumor progression

项目摘要

PROJECT SUMMARY The overarching goal of the project is to establish novel genomics and bioinformatics approaches to model patterns of DNA replication in cells. It is known that the patterns of DNA replication are intimately linked to the cell type. These differences between cell types are relevant to the integrity of the genome during cell type transitions. For example, we recently found that damage during DNA replication is increased during the induced transition from one cell type to another. However, there is a lack of methodology to observe replication patterns in human cells. DNA replication differs between different cell types in the location of initiation, the direction of fork progression, and the timing of initiation and completion. There is currently no method that can comprehensively map the progression of DNA replication to the genome. Because of the importance of DNA replication in cell proliferation, there is need for the development of such methods. To be able to examine the progression of DNA polymerases in human cells, we will develop a novel methodology to map DNA replication genome-wide, by incorporating nucleotide analogs during DNA replication, and sequencing the resulting DNA molecules by Nanopore sequencing and recording the electrical signals. In parallel, we will develop novel bioinformatics approaches to reliably examine the electrical signals and identify bases or regions of DNA replication, for comparison between different cell types, or between healthy and diseased tissues. Successful establishment of this technology will greatly increase our knowledge of replication, genetic stability and cell proliferation, and allow the community to characterize differences in the progression of DNA replication between cell types.

项目概要该项目的总体目标是建立新的基因组学和生物信息学方法来建模细胞中 DNA 复制的模式。众所周知，DNA复制的模式与DNA复制密切相关。细胞类型。细胞类型之间的这些差异与细胞类型过程中基因组的完整性有关过渡。例如，我们最近发现 DNA 复制过程中的损伤在诱导从一种细胞类型转变为另一种细胞类型。然而，缺乏观察复制模式的方法在人体细胞中。不同细胞类型之间的DNA复制在起始位置、复制方向上有所不同分叉进程以及启动和完成的时间。目前没有方法可以全面绘制 DNA 复制进程至基因组的图谱。因为DNA的重要性在细胞增殖复制过程中，有必要开发此类方法。为了能够检查人类细胞中 DNA 聚合酶的进展，我们将开发一种新的方法来绘制 DNA 复制图谱在基因组范围内，通过在 DNA 复制过程中掺入核苷酸类似物，并对所得 DNA 进行测序分子通过纳米孔测序并记录电信号。与此同时，我们将开发新颖的可靠地检查电信号并识别 DNA 碱基或区域的生物信息学方法复制，用于不同细胞类型之间或健康组织和患病组织之间的比较。成功的这项技术的建立将大大增加我们对复制、遗传稳定性和细胞的认识。增殖，并允许社区描述 DNA 复制进程中的差异细胞类型。