报告题目：scFMA: A Flexible Random Effects Model for DNA Methylation Analysis with scBS-seq Data

主讲人：黄希芬教授（云南师范大学）

时间：2025年10月27日（周一）15:00 p.m.

地点：北院卓远楼305会议室

主办单位：统计与数学学院

摘要：Background: Single-Cell Bisulfite Sequencing (scBS) has advanced rapidly because of its ability to study DNA methylation patterns at the level of individual cells. Since DNA methylation influences gene expression, a common approach involves identifying regions of differential methylation between cells to further explore transcriptional regulatory features and intercellular heterogeneity. However, this technique faces challenges such as limited sequencing depth and coverage, difficulties in processing large numbers of missing values, and the prevalence of extreme methylation rates (0 and 1) in single-cell data. These factors complicate accurate differential methylation analysis between cells.

Results: We develop a binomial model with flexible random effects for DNA methylation analysis. By combining the discrete approximation technique with the MM algorithm for model estimation and using the bootstrap method to construct a test statistic for model testing, the proposed scFMA method identifies differentially methylated regions without restricting the form of the random-effects distribution, which solves the limitation that the existing methods are prone to model misspecification that leads to estimation bias.

Conclusion: Numerical studies have demonstrated that scFMA can identify more differentially methylated regions while maintaining low false positive rates across various distribution settings. We applied this method to investigate the mechanisms of cell methylation in early embryos. Despite the challenges posed by sparse data and small sample sizes, our model effectively captures the actual data distribution and reveals critical biological information during embryonic development.

主讲人简介：

黄希芬，云南师范大学数学学院教授，主要从事生物医学中统计模型和快速算法等方面的研究，主持国家自然科学基金项目3项，发表论文20余篇。2019年和2023年先后获得云南省“兴滇英才支持计划”青年人才和云南省社会科学奖等奖项。