单细胞表观转录组学的统计建模实现了RNA甲基化的轨迹和调控推断。
Statistical modeling of single-cell epitranscriptomics enabled trajectory and regulatory inference of RNA methylation.
作者信息
Wang Haozhe, Wang Yue, Zhou Jingxian, Song Bowen, Tu Gang, Nguyen Anh, Su Jionglong, Coenen Frans, Wei Zhi, Rigden Daniel J, Meng Jia
机构信息
Department of Biosciences and Bioinformatics, Center for Intelligent RNA Therapeutics, Suzhou Key Laboratory of Cancer Biology and Chronic Disease, School of Science, XJTLU Entrepreneur College, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu 215123, China; Department of Computer Science, University of Liverpool, L7 8TX Liverpool, UK.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
出版信息
Cell Genom. 2025 Jan 8;5(1):100702. doi: 10.1016/j.xgen.2024.100702. Epub 2024 Dec 5.
As a fundamental mechanism for gene expression regulation, post-transcriptional RNA methylation plays versatile roles in various biological processes and disease mechanisms. Recent advances in single-cell technology have enabled simultaneous profiling of transcriptome-wide RNA methylation in thousands of cells, holding the promise to provide deeper insights into the dynamics, functions, and regulation of RNA methylation. However, it remains a major challenge to determine how to best analyze single-cell epitranscriptomics data. In this study, we developed SigRM, a computational framework for effectively mining single-cell epitranscriptomics datasets with a large cell number, such as those produced by the scDART-seq technique from the SMART-seq2 platform. SigRM not only outperforms state-of-the-art models in RNA methylation site detection on both simulated and real datasets but also provides rigorous quantification metrics of RNA methylation levels. This facilitates various downstream analyses, including trajectory inference and regulatory network reconstruction concerning the dynamics of RNA methylation.
作为基因表达调控的一种基本机制,转录后RNA甲基化在各种生物过程和疾病机制中发挥着多种作用。单细胞技术的最新进展使得能够在数千个细胞中同时对全转录组范围的RNA甲基化进行分析,有望为深入了解RNA甲基化的动态、功能和调控提供帮助。然而,如何最好地分析单细胞表观转录组学数据仍然是一个重大挑战。在本研究中,我们开发了SigRM,这是一个用于有效挖掘具有大量细胞的单细胞表观转录组学数据集的计算框架,例如由SMART-seq2平台的scDART-seq技术产生的数据集。SigRM不仅在模拟和真实数据集的RNA甲基化位点检测方面优于现有模型,还提供了严格的RNA甲基化水平定量指标。这有助于进行各种下游分析,包括关于RNA甲基化动态的轨迹推断和调控网络重建。