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通过纳米孔测序和引导式学习,通过非正规基的直接高吞吐量解卷

Mauricio Perez¹, Michiko Kimoto^2,3, Priscilla Rajakumar¹

¹Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore, Republic of Singapore.

Nature communications

|July 30, 2025

概括

研究人员使用纳米孔测序成功将合成的外核酸 (XNA) 与非正规基 (NCB) 进行了测序. 这一突破使不同应用的不同寻常的遗传材料的高通量分析成为可能.

科学领域:

生物技术是生物技术.
基因组学就是基因组学.
合成生物学合成生物学

背景情况:

非正规基 (NCB) 和合成的外核酸 (XNA) 在病毒基因组学,合成生物学和DNA存储方面具有潜力.
国家央行的高吞吐量测序一直是一个主要的限制,阻碍了它们的应用.

研究的目的:

通过使用纳米孔技术来证明含有 NCB 的 XNA 的强大高通量测序.
开发准确的AI模型来破译包含NCB的序列.

主要方法:

利用MinION纳米孔测序来分析与NCB的XNA,每个流细胞产生超过2.3x10^6的读数.
合成和测序了1,024个含有NCB的高纯度 (> 90%) 寡核酸的多样化池.
雇佣了启动模型和数据增强与拼接阅读用于AI模型培训.

主要成果:

从XNA与NCB与控制相比,实现了显著不同的信号 (中位数折叠变更>6x).
开发了可通用的人工智能模型,能够高精度 (> 80%) 和特异性 (99%) 解密包含NCB的序列.

结论:

纳米孔测序是一种多功能工具,用于与NCB询问像XNAs这样的不寻常核酸.
这一进步有可能改变遗传材料的研究,超越了正统的基础.

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