小柯机器人

德国欧洲分子生物学实验室Jan O. Korbel和德国萨尔大学Tobias Marschall研究组合作通过三通道处理，对单细胞的结构变化和复杂的重排进行了分析。这一研究成果在线发表在2019年12月23日出版的国际学术期刊《自然—生物技术》上。

研究人员建立了单细胞三通道处理（scTRIP）系统，这是一种将读取深度、模板链和单倍体相整合以全面发现单个细胞中结构变异（SV）的计算网络。研究人员测量了565个单细胞SV图谱，其中包括转化上皮细胞和患者来源的白血病样本，用于探索包括倒位、易位和复杂的DNA重排在内的丰富SV种类。白血病样本的分析显示，体细胞SV比细胞遗传核型分析、亚显微拷贝数改变、致癌拷贝中性重排和亚克隆性嗜铬菌病多四倍。与目前已有方法相比，单细胞三通道处理可以直接测量单个细胞中SV突变的过程，例如断裂-融合-桥环循环、克隆进化的研究、遗传嵌合体和SV形成机制的研究，这些都可以在精准医学上促进对疾病的分类。

据介绍，包括DNA片段缺失、重复、倒置和易位在内的SV是体细胞遗传变异的主要来源，并且会异常调控与癌症相关的途径。然而，在单细胞水平难以观察体细胞SV，因为拷贝数中性和复杂变体通常难以检测到。

附：英文原文

Title: Single-cell analysis of structural variations and complex rearrangements with tri-channel processing

Author: Ashley D. Sanders, Sascha Meiers, Maryam Ghareghani, David Porubsky, Hyobin Jeong, M. Alexandra C. C. van Vliet, Tobias Rausch, Paulina Richter-Pechaska, Joachim B. Kunz, Silvia Jenni, Davide Bolognini, Gabriel M. C. Longo, Benjamin Raeder, Venla Kinanen, Jrgen Zimmermann, Vladimir Benes, Martin Schrappe, Balca R. Mardin, Andreas E. Kulozik, Beat Bornhauser, Jean-Pierre Bourquin, Tobias Marschall, Jan O. Korbel

Issue&Volume: 2019-12-23

Abstract: Structural variation (SV), involving deletions, duplications, inversions and translocations of DNA segments, is a major source of genetic variability in somatic cells and can dysregulate cancer-related pathways. However, discovering somatic SVs in single cells has been challenging, with copy-number-neutral and complex variants typically escaping detection. Here we describe single-cell tri-channel processing (scTRIP), a computational framework that integrates read depth, template strand and haplotype phase to comprehensively discover SVs in individual cells. We surveyed SV landscapes of 565 single cells, including transformed epithelial cells and patient-derived leukemic samples, to discover abundant SV classes, including inversions, translocations and complex DNA rearrangements. Analysis of the leukemic samples revealed four times more somatic SVs than cytogenetic karyotyping, submicroscopic copy-number alterations, oncogenic copy-neutral rearrangements and a subclonal chromothripsis event. Advancing current methods, single-cell tri-channel processing can directly measure SV mutational processes in individual cells, such as breakage–fusion–bridge cycles, facilitating studies of clonal evolution, genetic mosaicism and SV formation mechanisms, which could improve disease classification for precision medicine.

DOI: 10.1038/s41587-019-0366-x

Source: https://www.nature.com/articles/s41587-019-0366-x

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：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex