arXiv:2510.27097cs.LGq-bio.GN2025-10

用贝叶斯模型解析月经周期中子宫内膜的细胞组成与基因表达变化。

Hierarchical Bayesian Model for Gene Deconvolution and Functional Analysis in Human Endometrium Across the Menstrual Cycle

  • 构建分层贝叶斯模型,从混合样本中分解出各细胞类型的表达与比例。
  • 发现上皮、基质和免疫细胞在月经周期中比例动态变化,基质细胞在分泌期表达蜕膜化标志物。
  • 对参考数据不匹配和噪声具有鲁棒性,适合研究激素驱动的组织动态变化。

混合组织的批量RNA测序会掩盖细胞类型特异性表达。为此,我们提出一种概率分层贝叶斯模型,利用高分辨率单细胞参考数据,将批量RNA-seq数据解卷积为各细胞类型的表达谱与比例。我们将该模型应用于人类子宫内膜跨月经周期的研究,该时期以激素驱动的细胞组成剧烈变化为特征。扩展框架实现了对细胞比例及细胞特异性基因表达变化的严谨推断。通过模拟和与现有方法比较,验证了模型结构、先验设定与推断策略的有效性。结果显示,上皮、基质和免疫细胞在不同月经阶段的比例发生动态变化,并识别出与子宫内膜功能相关的细胞类型特异性差异表达基因(如分泌期基质细胞中的蜕膜化标志物)。进一步的鲁棒性测试表明,该贝叶斯方法对参考数据不匹配和噪声具有较强抗干扰能力。最后,讨论了结果的生物学意义、对生育力与子宫内膜疾病潜在的临床价值,以及未来整合空间转录组学的方向。

原文摘要 · Abstract (English)

Bulk tissue RNA sequencing of heterogeneous samples provides averaged gene expression profiles, obscuring cell type-specific dynamics. To address this, we present a probabilistic hierarchical Bayesian model that deconvolves bulk RNA-seq data into constituent cell-type expression profiles and proportions, leveraging a high-resolution single-cell reference. We apply our model to human endometrial tissue across the menstrual cycle, a context characterized by dramatic hormone-driven cellular composition changes. Our extended framework provides a principled inference of cell type proportions and cell-specific gene expression changes across cycle phases. We demonstrate the model's structure, priors, and inference strategy in detail, and we validate its performance with simulations and comparisons to existing methods. The results reveal dynamic shifts in epithelial, stromal, and immune cell fractions between menstrual phases, and identify cell-type-specific differential gene expression associated with endometrial function (e.g., decidualization markers in stromal cells during the secretory phase). We further conduct robustness tests and show that our Bayesian approach is resilient to reference mismatches and noise. Finally, we discuss the biological significance of our findings, potential clinical implications for fertility and endometrial disorders, and future directions, including integration of spatial transcriptomics.

基因解卷积贝叶斯模型子宫内膜周期分析

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