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

TL;DR

This paper introduces a hierarchical Bayesian model that deconvolves bulk RNA-seq data into cell type-specific profiles and proportions, applied to human endometrial tissue to reveal cellular dynamics across menstrual phases.

Contribution

It presents a novel probabilistic framework for cell type deconvolution using single-cell references, enabling detailed analysis of tissue composition and gene expression changes.

Findings

Identified shifts in epithelial, stromal, and immune cell proportions across menstrual phases.

Detected cell-type-specific gene expression changes related to endometrial function.

Validated model robustness against reference mismatches and noise.

Abstract

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.