TSvelo: Comprehensive RNA velocity by modeling the cascade of gene regulation, transcription and splicing

Abstract RNA velocity approaches fit gene dynamics and infer cell fate by modeling the splicing process using single-cell RNA sequencing (scRNA-seq) data. However, due to short time scale of splicing, high noise and large complexity of data, existing RNA velocity methods often fail to precisely capture the complex velocity dynamics for individual gene and single cell, which makes its downstream analysis less reliable and less robust. We propose TSvelo, a comprehensive RNA velocity mathematics framework that can model the cascade of gene regulation, Transcription and Splicing using highly interpretable neural Ordinary Differential Equations (ODEs). TSvelo can precisely capture the transcription-unspliced-spliced 3D dynamics of all genes simultaneously, infer unified latent time shared by genes within single cell, and be applied to multi-lineage datasets. Experiments on six scRNA-seq datasets, including two multi-lineage datasets, demonstrate TSvelo’s superiority. Competing Interest Statement The authors have declared no competing interest. Footnotes Figure 2 revised. Results and discussion have been revised for better clarification.