DNAscent v2: detecting replication forks in nanopore sequencing data with deep learning.

BMC Genomics
Michael A Boemo

Abstract

Measuring DNA replication dynamics with high throughput and single-molecule resolution is critical for understanding both the basic biology behind how cells replicate their DNA and how DNA replication can be used as a therapeutic target for diseases like cancer. In recent years, the detection of base analogues in Oxford Nanopore Technologies (ONT) sequencing reads has become a promising new method to supersede existing single-molecule methods such as DNA fibre analysis: ONT sequencing yields long reads with high throughput, and sequenced molecules can be mapped to the genome using standard sequence alignment software. This paper introduces DNAscent v2, software that uses a residual neural network to achieve fast, accurate detection of the thymidine analogue BrdU with single-nucleotide resolution. DNAscent v2 also comes equipped with an autoencoder that interprets the pattern of BrdU incorporation on each ONT-sequenced molecule into replication fork direction to call the location of replication origins termination sites. DNAscent v2 surpasses previous versions of DNAscent in BrdU calling accuracy, origin calling accuracy, speed, and versatility across different experimental protocols. Unlike NanoMod, DNAscent v2 positively ident...Continue Reading

References

Jun 5, 2002·Genome Research·W James KentDavid Haussler
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Nov 29, 2011·Nucleic Acids Research·Cheuk C SiowConrad A Nieduszynski
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Apr 24, 2019·Nature Methods·Carolin A MüllerConrad A Nieduszynski
Jul 28, 2020·Nucleic Acids Research·Daniela GeorgievaDieter Egli

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Software Mentioned

NanoMod
MinKNOW
Origin
CUDA
DNAscent detect
Linux
IGV
Integrative Genomics Viewer ( IGV )
DNAscent
DNAscent forkSense

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