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Genome Biol. 2019 Nov 14;20(1):239. doi: 10.1186/s13059-019-1856-3.

NanoSatellite: accurate characterization of expanded tandem repeat length and sequence through whole genome long-read sequencing on PromethION.

Author information

1
Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, University of Antwerp-CDE, Universiteitsplein 1, B-2610, Antwerp, Belgium.
2
Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
3
Neuromics Support Facility, Center for Molecular Neurology, VIB - University of Antwerp, Antwerp, Belgium.
4
Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, University of Antwerp-CDE, Universiteitsplein 1, B-2610, Antwerp, Belgium. kristel.sleegers@uantwerpen.vib.be.
5
Biomedical Sciences, University of Antwerp, Antwerp, Belgium. kristel.sleegers@uantwerpen.vib.be.

Abstract

Technological limitations have hindered the large-scale genetic investigation of tandem repeats in disease. We show that long-read sequencing with a single Oxford Nanopore Technologies PromethION flow cell per individual achieves 30× human genome coverage and enables accurate assessment of tandem repeats including the 10,000-bp Alzheimer's disease-associated ABCA7 VNTR. The Guppy "flip-flop" base caller and tandem-genotypes tandem repeat caller are efficient for large-scale tandem repeat assessment, but base calling and alignment challenges persist. We present NanoSatellite, which analyzes tandem repeats directly on electric current data and improves calling of GC-rich tandem repeats, expanded alleles, and motif interruptions.

KEYWORDS:

ATP-binding cassette; Alzheimer’s disease; Dynamic time warping (DTW); Long-read whole genome sequencing; Member 7 (ABCA7); Sub-family A; Variable number tandem repeat (VNTR)

PMID:
31727106
PMCID:
PMC6857246
DOI:
10.1186/s13059-019-1856-3
[Indexed for MEDLINE]
Free PMC Article

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