通过开放的染色体足迹追踪无细胞DNA的组织起源
Lingguo Li1, Xiameizi Li1, Yongjie Li2
1College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
Communications biology
|November 25, 2025
概括
无血细胞DNA (cfDNA) 分析通过使用转录起点 (TSS) 覆盖范围来量化组织起源的新方法得到了推进. 这种组织贡献指数 (TCI) 为液体活检应用提供了具有成本效益的方法.
科学领域:
- 生物化学 生物化学
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 无血细胞DNA (cfDNA) 是用于疾病诊断和监测的液体活检的重要生物标志物.
- 目前的cfDNA组织贡献估计方法,通常使用甲基化标记物,可能会损害cfDNA并限制临床效用.
- 活跃基因的转录开始位点 (TSS) 附近减少cfDNA覆盖率与开放的染色质有关,但缺少跨组织图谱.
研究的目的:
- 开发和验证一种用于量化血cfDNA的组织特异性贡献的新方法.
- 创建一个全面的基因表达模式的跨组织地图,与cfDNA分析相关.
- 确定开发的疾病监测和结果预测方法的临床实用性.
主要方法:
- 在12个人类组织中鉴定了2549个组织特异性,高度表达的基因.
- 基于cfDNA TSS覆盖的组织贡献指数 (TCI) 的发展.
- 在cfDNA起源模型 (怀孕,移植) 中验证TCI,并在460名健康个体中建立参考间隔.
主要成果:
- 组织贡献指数 (TCI) 使用TSS覆盖率准确量化组织对血cfDNA的贡献.
- 在验证的cfDNA起源模型中,TCI表现出高准确度.
- 在一大群健康个体中建立了TCI的参考间隔.
结论:
- 已经建立了一种简单,具有成本效益的方法,用于使用TSS覆盖的cfDNA组织解卷.
- TCI方法推进了用于疾病检测和个性化医学的液体活检应用.
- TCI显示了监测组织损伤和预测患者结果的潜力.
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