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利用纳米孔测序的进步,用于对人类癌症模型的tRNA测序

Adva Kochavi¹, Arno Velds², Maya Suzuki³

¹Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands.

|November 5, 2025

概括

来自牛津纳米孔的新RNA测序技术 (RNA004) 准确地测量了转移RNA (tRNA) 水平和癌症中的修饰. 这一进展有助于对人类tRNAome在疾病中的理解.

科学领域:

分子生物学分子生物学
基因组学就是基因组学.
癌症研究癌症研究

背景情况:

转移RNAs (tRNAs) 调节蛋白质合成,它们的失调与癌症等人类疾病有关.
由于tRNAs的复杂结构和修改,尽管测序方面取得了进展,但人类tRNA景观仍未得到充分探索.
目前的方法在同时量化tRNA丰度和识别修改方面面临挑战.

研究的目的:

为了评估牛津纳米孔的RNA004化学与更新的多拉多基调用模型用于tRNA分析.
评估该技术在人类癌症模型中对tRNA量化和修改注释的能力.
探索这种方法在疾病背景下了解人类tRNAome的潜力.

主要方法:

使用了牛津纳米孔技术的RNA004化学和多拉多基地调用器模型.
在各种条件下将该技术应用于人类癌症细胞系.
分析了基调调用错误率,并使用多拉多的修改调用功能进行tRNA分析.

主要成果:

证明了tRNA表达变异的可重复识别,跨癌症细胞系和压力条件.
表明基调用错误率可以表明已知的tRNA修改,包括Wybutosine.
使用更新的多拉多修改调用功能,成功预测了常见的tRNA修改.

结论:

RNA004 tRNA-seq提供了一种强大的工具,用于同时分析tRNA丰度和修改.
这项技术有可能大大提高对癌症和其他疾病中人类tRNAome的理解.
确定了tRNA测序和修饰分析未来方法开发的局限性和挑战.

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