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纳米孔测序技术科可分析短串联重复序列及其甲基化
作者:小柯机器人 发布时间:2019/11/19 14:59:47

德国马克斯·普朗克分子遗传学研究所Franz-Josef Mller研究组近日取得一项新成果。他们利用纳米孔测序实现对短串联重复序列扩增及其甲基化状态的分析技术。这一研究成果2019年11月18日在线发表在国际学术期刊《自然—生物技术》上。

研究人员报道了一种基于CRISPR–Cas的纳米孔测序富集策略,并结合了原始信号分析算法。 这一被称为STRique的短串联重复序列鉴定、定量和评估方法,将常规的纳米孔读取序列映射与原始信号比对相结合,以定位重复边界,并采用了基于隐马尔可夫模型的重复计数机制。 研究人员展示了重复数目的精确量化,以及在重复扩增和邻近区域的CpG甲基化状态的检测。这一方法能够研究以前无法获取的基因组区域及其表观遗传标记。

据介绍,短串联重复序列的扩增是已经与几种神经精神病和其他疾病有关的遗传变异,但是其利用聚合酶检测的评估方法仍然具有挑战性。

附:英文原文

Title: Analysis of short tandem repeat expansions and their methylation state with nanopore sequencing

Author: Pay Giesselmann, Bjrn Brndl, Etienne Raimondeau, Rebecca Bowen, Christian Rohrandt, Rashmi Tandon, Helene Kretzmer, Gnter Assum, Christina Galonska, Reiner Siebert, Ole Ammerpohl, Andrew Heron, Susanne A. Schneider, Julia Ladewig, Philipp Koch, Bernhard M. Schuldt, James E. Graham, Alexander Meissner, Franz-Josef Mller

Issue&Volume: 2019-11-18

Abstract: Expansions of short tandem repeats are genetic variants that have been implicated in several neuropsychiatric and other disorders, but their assessment remains challenging with current polymerase-based methods1,2,3,4. Here we introduce a CRISPR–Cas-based enrichment strategy for nanopore sequencing combined with an algorithm for raw signal analysis. Our method, termed STRique for short tandem repeat identification, quantification and evaluation, integrates conventional sequence mapping of nanopore reads with raw signal alignment for the localization of repeat boundaries and a hidden Markov model-based repeat counting mechanism. We demonstrate the precise quantification of repeat numbers in conjunction with the determination of CpG methylation states in the repeat expansion and in adjacent regions at the single-molecule level without amplification. Our method enables the study of previously inaccessible genomic regions and their epigenetic marks.

DOI: 10.1038/s41587-019-0293-x

Source: https://www.nature.com/articles/s41587-019-0293-x

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex