贝斯蒂什:一种扩散近似框架,用于推断克隆血液形成中的选择和突变
bioRxiv : the preprint server for biology
|February 9, 2026
概括
克隆性造血 (CH) 涉及突变干细胞的扩张. 我们开发了BESTish,这是一个贝叶斯的方法来建模CH进化和分析变异性等位基因频率 (VAF) 动态,揭示患者特定的突变行为.
科学领域:
- 血液学 血液学 血液学
- 计算生物学 计算生物学
- 遗传学 是一个遗传学.
背景情况:
- 克隆性造血 (CH) 是由造血干细胞 (HSC) 的体性突变驱动的.
- 了解CH演变需要准确地建模变异基频率 (VAF) 动态.
- 环境因素可能会影响HSC适应性和克隆扩张.
研究的目的:
- 开发一种新的随机模型来分析CH轨迹.
- 创建一个高效和准确的贝叶斯推理方法 (BESTish) 用于CH驱动器分析.
- 量化CH中的突变适应性,速率和环境影响.
主要方法:
- 开发了野生型和突变型HSC的依赖状态的随机模型.
- 衍生平均场动力学和高斯 - 马尔科夫近似对VAF.
- 介绍了BESTish,这是一个使用VAF数据的闭式分布的贝叶斯推理方法.
主要成果:
- 平均VAF轨迹遵循一个由选择性优势影响的后勤形式.
- 环境因素影响VAF变量和自共变量,而不是平均轨迹.
- 在研究中,BESTish提供了一致的突变适应性和速率估计.
- 在突变选择和非静态环境中确定了患者特异性.
结论:
- BESTish提供了一个统一的框架来量化CH的演变.
- 该方法准确地估计了关键参数,如突变适应性和环境强度.
- 揭示患者特定的克隆动态,并确定促进生长环境中的突变.
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