Mapping and phasing of structural variation in patient genomes using nanopore sequencing

By Mircea Cretu Stancu, Markus J. van Roosmalen, I. Renkens, Marleen M Nieboer, Sjors Middelkamp, J. de Ligt, Giulia Pregno, D. Giachino, G. Mandrile, J. Espejo Valle-Inclan and 7 more. Nature Communications, 2017

370 citations recorded by the source corpus.

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.

Subfields: Artificial Intelligence, Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2948751b1ef3c2ba1b39f0916be26e6a70f52384

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Citations in the corpus

From squiggle to basepair: computational approaches for improving nanopore sequencing read accuracy (2018, methodology): “This accuracy has improved over recent years to reach approximately 85% [3, 5, 11, 12] (Fig.”
Opportunities and challenges in long-read sequencing data analysis (2020, background): “Obtaining deep coverage of mammalian-sized genomes with long reads remains costly; however, modest coverage may be sufficient: 8.6 × SMRT sequencing [14] and 15–17 × nanopore sequencing [80, 81] have been shown to be effective in detecting pathogenic variants in humans.”
Structural variant calling: the long and the short of it (2019, methodology): “Due to the complexity, only few studies were able to do this so far with a success of 78.7%, even though parental genomic data was used [59].”