DNAscent v2: detecting replication forks in nanopore sequencing data with deep learning.
DNAscent v2: detecting replication forks in nanopore sequencing data with deep learning.
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DOI：
10.1186/s12864-021-07736-6
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发表时间：
2021-06-09
期刊：
影响因子：
4.4
通讯作者：
Boemo MA
中科院分区：
文献类型：
--
作者：
Boemo MA
以高通量和单分子分辨率测量 DNA 复制动态对于了解细胞如何复制 DNA 背后的基础生物学以及 DNA 复制如何用作癌症等疾病的治疗靶标至关重要。近年来，牛津纳米孔技术（ONT）测序读数中碱基类似物的检测已成为取代现有单分子方法（例如DNA纤维分析）的一种有前景的新方法：ONT测序产生高通量的长读数，并且可以使用标准序列比对软件将已测序的分子映射到基因组。本文介绍了 DNAscent v2 软件，该软件使用残差神经网络以单核苷酸分辨率实现胸苷类似物 BrdU 的快速、准确检测。 DNAscent v2 还配备了自动编码器，可将每个 ONT 测序分子上的 BrdU 掺入模式解释为复制叉方向，以调用复制起点终止位点的位置。 DNAscent v2 在 BrdU 识别准确度、来源识别准确度、速度以及跨不同实验方案的多功能性方面超越了 DNAscent 的早期版本。与 NanoMod 不同，DNAscent v2 无需对未修饰的 DNA 进行测序即可准确识别 BrdU。与 RepNano 不同，DNAscent v2 以单核苷酸分辨率调用 BrdU，并从相同的测序数据中检测到比 RepNano 更多的起源。 DNAscent v2 是开源的，可从 https://github.com/MBoemo/DNAscent 获取。本文表明 DNAscent v2 是复制叉动力学高通量、单分子检测领域最先进的技术。 DNAscent v2 的这些改进标志着以单分子分辨率测量大型基因组中 DNA 复制动态的重要一步。展望未来，单核苷酸分辨率 BrdU 识别准确性的提高也将使 DNAscent v2 扩展到基因组稳定性研究的其他领域，特别是 DNA 修复的检测。在线版本包含可在 (10.1186/s12864-021-07736-6) 获取的补充材料。
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 identifies BrdU without the need for sequencing unmodified DNA. Unlike RepNano, DNAscent v2 calls BrdU with single-nucleotide resolution and detects more origins than RepNano from the same sequencing data. DNAscent v2 is open-source and available at https://github.com/MBoemo/DNAscent. This paper shows that DNAscent v2 is the new state-of-the-art in the high-throughput, single-molecule detection of replication fork dynamics. These improvements in DNAscent v2 mark an important step towards measuring DNA replication dynamics in large genomes with single-molecule resolution. Looking forward, the increase in accuracy in single-nucleotide resolution BrdU calls will also allow DNAscent v2 to branch out into other areas of genome stability research, particularly the detection of DNA repair. The online version contains supplementary material available at (10.1186/s12864-021-07736-6).
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