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

Arne De Roeck; Wouter De Coster; Liene Bossaerts; Rita Cacace; Tim De Pooter; Jasper Van Dongen; Svenn D'Hert; Peter De Rijk; Mojca Strazisar; Christine Van Broeckhoven; Kristel Sleegers

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

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

Authors

Arne De Roeck^{1

2}, Wouter De Coster^{1

2}, Liene Bossaerts^{1

2}, Rita Cacace^{1

2}, Tim De Pooter³, Jasper Van Dongen^{1

2}, Svenn D'Hert³, Peter De Rijk³, Mojca Strazisar³, Christine Van Broeckhoven^{1

2}, Kristel Sleegers^{4

5}

Affiliations

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. [email protected].
⁵ Biomedical Sciences, University of Antwerp, Antwerp, Belgium. [email protected].

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).

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

ATP-Binding Cassette Transporters / genetics
Algorithms
Feasibility Studies
Genome, Human*
Genomics / methods*
High-Throughput Nucleotide Sequencing*
Humans
Minisatellite Repeats
Tandem Repeat Sequences*

Substances

ABCA7 protein, human
ATP-Binding Cassette Transporters