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在临床相关样本中进行酶和双硫酸DNA甲基化分析的全面比较

Barrett Nuttall¹, Daniel L Karl^2,3, Kathleen Burke¹

¹Early Oncology Translational Medicine, Genomics, Oncology R&D, AstraZeneca, Waltham, MA, USA.

Clinical epigenetics

|October 4, 2025

概括

酶性DNA甲基化测序为临床样本提供了比二硫酸盐转化更高的性能. 这种方法对将15型白血素甲基化变化与慢性淋巴细胞白血病的治疗反应联系起来有希望.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
基因组学就是基因组学.
分子生物学分子生物学

背景情况:

双硫酸盐转化是DNA甲基化分析的标准,但会损害DNA,并且对于临床样本来说是不理想的.
酶方法为DNA甲基化测序提供了一个替代方案.
临床样本,如甲固定,嵌和循环的自由血DNA,对二硫酸盐转化构成挑战.

研究的目的:

为了全面比较二硫酸盐和酶甲基化测序方法.
评估这些方法在临床相关的患者样本和细胞系中的性能.
报告第一个临床全基因组甲基化测序,使用慢性淋巴细胞白血病患者的酶方法.

主要方法:

商业上可用的双硫酸盐和酶甲基化测序试验的比较.
对受控参考材料和临床相关样本的分析.
首次临床全基因组甲基化测序 (WGMS) 在慢性淋巴细胞白血病 (CLL) 患者队列中.

主要成果:

酶甲基化测序显示与二硫酸盐数据的高度一致.
酶方法显示出优越的测序指标,包括更高的唯一读数,减少DNA碎片化和增加图书馆产量.
与二硫相比,酶转化产生较差的甲基化阵列数据.
酶测序的质量提高使得可靠的临床样本管道成为可能,包括在cfDNA中进行向测序.

结论:

酶甲基化测序方法有助于开发临床样本管道.
在CLL临床试验队列中发现了interleukin-15甲基化变化和acalabrutinib治疗反应之间的潜在联系.
这项研究强调了在临床环境中用于DNA甲基化分析的酶方法的优势.

关键词:

双硫酸盐序列测序双硫酸盐序列测序慢性淋巴细胞白血病慢性淋巴细胞白血病酶性甲基化测序的序列化甲基化甲基化甲基化有针对性的甲基化测序.

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