Nanopore based profiling of epigenetic state

项目概述：虽然一个参考人类基因组，甚至是优秀的表征， 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（> 10 kb）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。

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.