1. NanoSatellite: accurate characterization of expanded tandem repeat length and sequence through whole genome long-read sequencing on PromethION
- Author
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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, and Kristel Sleegers
- Subjects
Long-read whole genome sequencing ,Dynamic time warping (DTW) ,Variable number tandem repeat (VNTR) ,ATP-binding cassette ,Sub-family A ,Member 7 (ABCA7) ,Biology (General) ,QH301-705.5 ,Genetics ,QH426-470 - Abstract
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.
- Published
- 2019
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