Dataset Information

Noise-cancelling repeat finder: uncovering tandem repeats in error-prone long-read sequencing data.

ABSTRACT:

Summary

Tandem DNA repeats can be sequenced with long-read technologies, but cannot be accurately deciphered due to the lack of computational tools taking high error rates of these technologies into account. Here we introduce Noise-Cancelling Repeat Finder (NCRF) to uncover putative tandem repeats of specified motifs in noisy long reads produced by Pacific Biosciences and Oxford Nanopore sequencers. Using simulations, we validated the use of NCRF to locate tandem repeats with motifs of various lengths and demonstrated its superior performance as compared to two alternative tools. Using real human whole-genome sequencing data, NCRF identified long arrays of the (AATGG)n repeat involved in heat shock stress response.

Availability and implementation

NCRF is implemented in C, supported by several python scripts, and is available in bioconda and at https://github.com/makovalab-psu/NoiseCancellingRepeatFinder.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Harris RS

PROVIDER: S-EPMC6853708 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Noise-cancelling repeat finder: uncovering tandem repeats in error-prone long-read sequencing data.

Harris Robert S RS Cechova Monika M Makova Kateryna D KD

Bioinformatics (Oxford, England) 20191101 22

<h4>Summary</h4>Tandem DNA repeats can be sequenced with long-read technologies, but cannot be accurately deciphered due to the lack of computational tools taking high error rates of these technologies into account. Here we introduce Noise-Cancelling Repeat Finder (NCRF) to uncover putative tandem repeats of specified motifs in noisy long reads produced by Pacific Biosciences and Oxford Nanopore sequencers. Using simulations, we validated the use of NCRF to locate tandem repeats with motifs of v ...[more]

PMID: 31290946

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Project description:Disease-associated trinucleotide repeats form secondary DNA structures that interfere with replication and repair. Replication has been implicated as a mechanism that can cause repeat expansions and contractions. However, because structure-forming repeats are also replication barriers, it has been unclear whether the instability occurs due to slippage during normal replication progression through the repeat, slippage or misalignment at a replication stall caused by the repeat, or during subsequent replication of the repeat by a restarted fork that has altered properties. In this study, we have specifically addressed the fidelity of a restarted fork as it replicates through a CAG/CTG repeat tract and its effect on repeat instability. To do this, we used a well-characterized site-specific replication fork barrier (RFB) system in fission yeast that creates an inducible and highly efficient stall that is known to restart by recombination-dependent replication (RDR), in combination with long CAG repeat tracts inserted at various distances and orientations with respect to the RFB. We find that replication by the restarted fork exhibits low fidelity through repeat sequences placed 2-7 kb from the RFB, exhibiting elevated levels of Rad52- and Rad8ScRad5/HsHLTF-dependent instability. CAG expansions and contractions are not elevated to the same degree when the tract is just in front or behind the barrier, suggesting that the long-traveling Polδ-Polδ restarted fork, rather than fork reversal or initial D-loop synthesis through the repeat during stalling and restart, is the greatest source of repeat instability. The switch in replication direction that occurs due to replication from a converging fork while the stalled fork is held at the barrier is also a significant contributor to the repeat instability profile. Our results shed light on a long-standing question of how fork stalling and RDR contribute to expansions and contractions of structure-forming trinucleotide repeats, and reveal that tolerance to replication stress by fork restart comes at the cost of increased instability of repetitive sequences.

Dataset Information

Noise-cancelling repeat finder: uncovering tandem repeats in error-prone long-read sequencing data.

Summary

Availability and implementation

Supplementary information

Publications

Noise-cancelling repeat finder: uncovering tandem repeats in error-prone long-read sequencing data.

Similar Datasets

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