Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads

Tandemly repeated DNA is highly mutable and causes at least 31 diseases, but it is hard to detect pathogenic repeat expansions genome-wide. Here, we report robust detection of human repeat expansions from careful alignments of long but error-prone (PacBio and nanopore) reads to a reference genome. O...

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Bibliographic Details
Published inGenome Biology Vol. 20; no. 1; pp. 58 - 17
Main Authors Mitsuhashi, Satomi, Frith, Martin C, Mizuguchi, Takeshi, Miyatake, Satoko, Toyota, Tomoko, Adachi, Hiroaki, Oma, Yoko, Kino, Yoshihiro, Mitsuhashi, Hiroaki, Matsumoto, Naomichi
Format Journal Article
LanguageEnglish
Published England BioMed Central 19.03.2019
BMC
Subjects
Bioinformatics
Cell division
Deoxyribonucleic acid
Disease
DNA
Genomes
Genotypes
Localization
Long-read sequencing
Method
Methods
Mutation
Nanopore
PacBio
Proteins
Repeat diseases
Tandem repeat
Repeat diseases
Long-read sequencing
Nanopore
Tandem repeat
PacBio
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Summary:Tandemly repeated DNA is highly mutable and causes at least 31 diseases, but it is hard to detect pathogenic repeat expansions genome-wide. Here, we report robust detection of human repeat expansions from careful alignments of long but error-prone (PacBio and nanopore) reads to a reference genome. Our method is robust to systematic sequencing errors, inexact repeats with fuzzy boundaries, and low sequencing coverage. By comparing to healthy controls, we prioritize pathogenic expansions within the top 10 out of 700,000 tandem repeats in whole genome sequencing data. This may help to elucidate the many genetic diseases whose causes remain unknown.
ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-019-1667-6