Mapping and phasing of structural variation in patient genomes using nanopore sequencing.
Mapping and phasing of structural variation in patient genomes using nanopore sequencing.
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DOI：
10.1038/s41467-017-01343-4
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发表时间：
2017-11-06
影响因子：
16.6
通讯作者：
Kloosterman WP
中科院分区：
文献类型：
--
作者：
Cretu Stancu M;van Roosmalen MJ;Renkens I;Nieboer MM;Middelkamp S;de Ligt J;Pregno G;Giachino D;Mandrile G;Espejo Valle-Inclan J;Korzelius J;de Bruijn E;Cuppen E;Talkowski ME;Marschall T;de Ridder J;Kloosterman WP
尽管基因组学技术有所改进，但从短读数测序中检测结构变异(SVS)仍然面临挑战，特别是对于复杂的变异。在这里，我们使用Minion纳米孔测序仪和一种新的计算流水线-NanoSV分析了两名先天性异常患者的基因组。我们证明，在检测从头染色质重排方面，纳米孔长读数优于短读数。长的读数还可以有效地对遗传变异进行阶段划分，我们利用这一点来确定所有从头开始的染色质断裂点的亲本来源，并解决这些复杂重排的结构。此外，对遗传SVS的全基因组监测揭示了短读数据集中遗漏的新变异，其中很大一部分是反转录转座子插入。我们提供了使用纳米孔测序仪对患者基因组测序的第一次探索，并展示了长读测序在临床和研究应用中绘制和分阶段SVS的价值。短读测序技术很难检测到结构变异，特别是当变异高度复杂的时候。在这里，作者使用Minion纳米孔测序仪分析了两个患者的基因组，并开发了NanoSV来定位已知的和新的结构变异在长阅读数据中。
Despite improvements in genomics technology, the detection of structural variants (SVs) from short-read sequencing still poses challenges, particularly for complex variation. Here we analyse the genomes of two patients with congenital abnormalities using the MinION nanopore sequencer and a novel computational pipeline—NanoSV. We demonstrate that nanopore long reads are superior to short reads with regard to detection of de novo chromothripsis rearrangements. The long reads also enable efficient phasing of genetic variations, which we leveraged to determine the parental origin of all de novo chromothripsis breakpoints and to resolve the structure of these complex rearrangements. Additionally, genome-wide surveillance of inherited SVs reveals novel variants, missed in short-read data sets, a large proportion of which are retrotransposon insertions. We provide a first exploration of patient genome sequencing with a nanopore sequencer and demonstrate the value of long-read sequencing in mapping and phasing of SVs for both clinical and research applications. The detection of structural variants can be difficult with short-read sequencing technology, especially when variants are highly complex. Here, the authors use a MinION nanopore sequencer to analyse two patient genomes and develop NanoSV to map known and novel structural variants in long read data.