情侣:重建单细胞开放色素景观用于转录因子规律映射
1School of Information Science and Technology, Northeast Normal University, Jilin, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|March 14, 2026
概括
我们开发了PAIR,这是一个概率框架,通过恢复染色体可访问性配置文件来增强单细胞ATAC-seq数据. 这种方法改善了细胞状态识别和监管程序推断,克服了数据稀疏性和噪声,以获得更好的生物洞察力.
科学领域:
- 基因组学和生物信息学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 计算生物学 计算生物学
背景情况:
- 单细胞ATAC-seq (scATAC-seq) 提供了细胞分辨率的染色质可访问性,但受到低序列深度,稀疏性和缺失数据的困扰.
- 这些局限性阻碍了准确的细胞状态分类和转录因子 (TF) 监管网络的推断.
- 现有的方法很难有效地解决scATAC-seq数据中固有的噪音和稀疏性.
研究的目的:
- 引入PAIR,一种新的概率框架,旨在恢复和归算scATAC-seq可访问性配置文件.
- 提高细胞状态划分的稳定性,并从稀疏的scATAC-seq数据推断TF监管程序.
- 提供一个计算工具,增强scATAC-seq在生物发现中的实用性.
主要方法:
- PAIR使用双分图形编码器来学习单元格和峰值的联合表示.
- 它包含一个变化的潜层,以模拟稀疏和杂测量的不确定性.
- 两个解码器 (定性和定量) 分别使用负二项式概率重建了细胞峰值发生率和可访问性计数.
主要成果:
- PAIR显著提高了聚类性能,并提高了对模拟和真实scATAC-seq数据集的差异性可访问性分析的灵敏度.
- 该框架有效地恢复了来自推动者近端和远端元素的监管信号.
- 来自PAIR的峰值嵌入方便了以位置为中心的调节性询问,揭示了结构化的调节性社区,并确定了临床相关的基因组.
结论:
- PAIR提供了一个强大的概率框架,用于赋值和增强scATAC-seq数据,克服关键的技术限制.
- 该方法明显改善了下游分析,包括细胞状态分类和监管网络推断.
- 通过scATAC-seq实验,PAIR能够对基因调节和细胞专业化进行更深入的生物学洞察.
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