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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：
9895852
负责人：
Winston George Timp
金额：
$ 49.3万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-19 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9895852
关键词：
Address Adenine Algorithms Architecture Autoimmune Diseases Binding Proteins Binding Sites Biological Cell division Cells Chemical Structure Chemicals Chromatin Chromatin Structure Computing Methodologies Cytosine DNA DNA Modification Process DNA Sequence DNA Sequence Alteration DNA sequencing Data Detection Development Devices Epigenetic Process Face Frequencies Gene Expression Gene Expression Regulation Generations Genetic Genetic Transcription Genome Grant Heritability Heterogeneity Histones Human Cell Line Human Genome Label Logistics Malignant Neoplasms Measurement Measures Memory Methodology Methods Methylation Modification Mutation Normal tissue morphology Nuclear Nuclear Structure Nucleotides Organism Pathway interactions Pattern Phase Phenotype Population Post-Translational Protein Processing Proteins Reaction Role Sampling Signal Transduction Somatic Cell Statistical Methods Statistical Models Stimulus Stretching Structure Technology Time Tissues Training Translating Translations Untranslated RNA Validation Variant autism spectrum disorder base combinatorial computerized tools demethylation direct application epigenetic profiling epigenetic variation epigenome human disease human reference genome innovation methylome nanopore novel response sequencing platform single molecule stem cells

项目摘要

Project Summary: Though a reference human genome and even excellent characterization of the epigenome (ENCODE, Epigenetics Roadmap) has been generated, the significance of noncoding genetic or epigenetic changes is still far from clear. With the advent of affordable DNA- sequencing technologies, methods have been developed for examining nuclear organization, chromatin state/histone post translation modifications, chromatin accessibility and methylation state. But these methods do not directly interrogate the DNA strand, and the reads are typically too short to provide critical correlative information. We propose the development of a novel epigenetic characterization methodology, fundamentally through the practical implementation of the sequencing of modified bases using a nanopore sequencing platform. Nanopore sequencing directly probes the chemical structure of the molecule in the pore with exquisite sensitivity. Its long reads enable correlation of epigenetic state over large (>10kb) stretches of the genome; each of these reads originates from a single cell, probing the epigenetic heterogeneity of the sample.

项目摘要：尽管有参考人类基因组甚至出色的表征，表观基因组（ENCODE，表观遗传学路线图）已经产生，非编码遗传或表观遗传变化仍远不清楚。随着廉价DNA的出现测序技术，已经开发了用于检查核组织的方法，染色质状态/组蛋白翻译后修饰、染色质可及性和甲基化状态但是这些方法不直接询问DNA链，并且读数通常是太短，无法提供关键的相关信息。我们提议写一部小说表观遗传表征方法，从根本上通过实际实施，使用纳米孔测序平台对修饰的碱基进行测序。纳米孔测序以极高的灵敏度直接探测孔隙中分子的化学结构。其长读段使得表观遗传状态能够在基因组的大（> 10kb）延伸上相关;每个这些读数中的一个源自单个细胞，探测样品的表观遗传异质性。