Genome-wide inference of transcription kinetics from single-cell snapshot data

：张家军（中山大学）
：2023-03-20 15:00
：腾讯会议：579-922-4321（无密码）

报告人：张家军（中山大学）

时  间：2023年3月20日15：00-16：30

地  点：腾讯会议：579-922-4321（无密码）

内容摘要:

Gene expression in mammalian cells is highly variable and episodic, resulting in a series of discontinuous bursts of mRNAs. A challenge is to understand how static promoter architecture and dynamic feedback regulations dictate bursting on a genome-wide scale. Although single-cell RNA sequencing (scRNA-seq) provides an opportunity to address this challenge, effective analytical methods are scarce. We developed an interpretable and scalable inference framework, which combined experimental data with a mechanistic model to infer transcriptional burst kinetics (sizes and frequencies) and feedback regulations. Applying this framework to scRNA-seq data generated from embryonic mouse fibroblast cells, we found Simpson's paradoxes, i.e. genome-wide burst kinetics exhibit different characteristics in two cases without and with distinguishing feedback regulations. We also showed that feedbacks differently modulate burst frequencies and sizes and conceal the effects of transcription start site distributions on burst kinetics. Notably, only in the presence of positive feedback, TATA genes are expressed with high burst frequencies and enhancer–promoter interactions mainly modulate burst frequencies. The developed inference method provided a flexible and efficient way to investigate transcriptional burst kinetics and the obtained results would be helpful for understanding cell development and fate decision.

个人简介：

张家军，中山大学数学学院教授，博士生导师。2009年在中山大学数学学院获得博士学位。致力于数学与生命科学交叉研究，研究方向包括计算系统生物学、生物信息学和生物统计等。在国际重要学术期刊如PNAS、Physical Review Letters、Nucleic Acids Research、PLoS Computational Biology、Biophysical Journal和SIAM Journal on Applied Mathematics等发表论文50余篇。主持国家自然科学基金面上项目、国家自然科学青年科学基金项目、广州市珠江科技新星专项等多项科研项目，并作为骨干成员参与多项国家自然科学重点项目等科研项目。现任中国工业与应用数学学会数学生命科学专业委员会副秘书长、广东省计算数学学会副理事长、中国细胞生物学学会功能基因组信息学与系统生物学分会理事、广东省工业与应用数学学会常务理事、广东省高性能计算学会理事。获2020世界华人数学家联盟最佳论文奖（若琳奖）。

 

联系人：周达