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Nanopore based profiling of epigenetic state

基于纳米孔的表观遗传状态分析

基本信息

批准号：
10631186
负责人：
Winston George Timp
金额：
$ 62.4万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10631186
关键词：
Address Antibodies Area Azides Bar Codes Binding Binding Proteins Binding Sites Biology Cells Chemicals Chromatin Classification Collaborations Color Complex Country Cytosine DNA DNA Modification Process DNA Sequence DNA Sequence Alteration DNA sequencing DNA-Binding Proteins DNA-Protein Interaction Data Detection Development Educational process of instructing Enhancers Enzymes Epigenetic Process Funding Gene Expression Gene Expression Regulation Generations Genetic Transcription Genome Grant Heterogeneity Human Genome Individual Label Length Malignant Neoplasms Maps Measurement Measures Methodology Methods Methylation Methyltransferase Modification Molecular Mutation Nuclear Organic Chemistry Organism Peptide Sequence Determination Phase Phenotype Population Proteins RNA Repetitive Sequence Resolution Sampling Signal Transduction Site Somatic Cell Stimulus Technology Time Tissues Training Translating Variant Work analysis pipeline base cofactor combinatorial epigenetic profiling epigenetic variation epigenome epigenomics glycosylation histone modification human disease human reference genome insight nanopore novel promoter response sequencing platform single molecule stem cells tool

项目摘要

Project Summary: Though a reference human genome and even excellent characterization of the epigenome (ENCODE, Epigenetics Roadmap, 4D Nucleome Project) has been generated, we still lack a clear understanding of how the different facets of the epigenome collaborate to control gene expression. With the advent of affordable DNA-sequencing technologies, methods have been developed for examining nuclear organization, protein-DNA interaction, chromatin accessibility, and methylation state. But these methods generally interrogate only one aspect of the epigenome at a time and reads are typically too short to provide critical correlative information. We propose the development of a novel epigenetic characterization methodology, in this round of funding focusing on protein- DNA interaction through leveraging the long reads and modified bases detectable with a nanopore sequencing platform. We will enhance the signal from subtle modifications being used to profile protein-DNA interactions. We are developing a method to insert sequence tags (nanoTUBI) near the sites of protein-DNA binding. And we will implement these methods focusing on long read sequencing, gaining insights into long correlative measurements and heretofore unexplored repetitive areas, phasing the entire epigenome. These tools and analysis pipelines will grant new insights into mechanisms of gene regulation, as well as their implications for human disease.

项目总结：通过参考人类基因组，甚至很好地描述了表观基因组(ENCODE，表观遗传学路线图，4D核基因组计划)已经产生，我们仍然缺乏明确的认识表观基因组的各个方面协同控制基因的表达。随着负担得起的DNA测序技术的出现已经开发出检测核组织、蛋白质-DNA相互作用、染色质可及性和甲基化状态。但这些方法通常只询问表观基因组和阅读通常太短，不能提供关键的相关信息。我们建议开发一种新的表观遗传学表征方法，在这一轮以蛋白质为重点的资助中通过利用纳米孔测序可检测到的长阅读和修饰碱基来实现DNA相互作用站台。我们将增强用于描述蛋白质-DNA相互作用的微妙修饰的信号。我们正在开发一种在蛋白质-DNA结合位点附近插入序列标签(NanTUBI)的方法。而我们我将实施这些方法，重点放在长阅读排序上，获得对长相关的见解测量和迄今未探索的重复区域，分阶段完成整个表观基因组。这些工具和分析管道将给予对基因调控机制的新见解，以及它们对人类疾病。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Beyond assembly: the increasing flexibility of single-molecule sequencing technology.

DOI：
10.1038/s41576-023-00600-1
发表时间：
2023-09
期刊：
Nature reviews. Genetics
影响因子：
0
作者：
Hook PW;Timp W
通讯作者：
Timp W

Single-molecule approaches for DNA damage detection and repair: A focus on Repair Assisted Damage Detection (RADD).

DOI：
10.1016/j.dnarep.2023.103533
发表时间：
2023-09
期刊：
DNA REPAIR
影响因子：
3.8
作者：
Zur, Tahir Detinis;Deek, Jasline;Ebenstein, Yuval
通讯作者：
Ebenstein, Yuval

Genome and transcriptome of a pathogenic yeast, Candida nivariensis.

DOI：
10.1093/g3journal/jkab137
发表时间：
2021-07-14
期刊：
G3 (Bethesda, Md.)
影响因子：
0
作者：
Fan Y;Gale AN;Bailey A;Barnes K;Colotti K;Mass M;Morina LB;Robertson B;Schwab R;Tselepidakis N;Timp W
通讯作者：
Timp W

PRINCESS: comprehensive detection of haplotype resolved SNVs, SVs, and methylation.

DOI：
10.1186/s13059-021-02486-w
发表时间：
2021-09-14
期刊：
Genome biology
影响因子：
12.3
作者：
Mahmoud M;Doddapaneni H;Timp W;Sedlazeck FJ
通讯作者：
Sedlazeck FJ

Dam Assisted Fluorescent Tagging of Chromatin Accessibility (DAFCA) for Optical Genome Mapping in Nanochannel Arrays.

DOI：
10.1021/acsnano.2c12755
发表时间：
2023-05-23
期刊：
ACS NANO
影响因子：
17.1
作者：
Nifker, Gil;Grunwald, Assaf;Margalit, Sapir;Tulpova, Zuzana;Michaeli, Yael;Har-Gil, Hagai;Maimon, Noy;Roichman, Elad;Schuetz, Leonie;Weinhold, Elmar;Ebenstein, Yuval
通讯作者：
Ebenstein, Yuval