Chen Yuhao, Zhang Yan, Gan Jiaqi, Ni Ke, Chen Ming, Bahar Ivet, Xing Jianhua
Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Res Sq. 2025 Jan 15:rs.3.rs-5613372. doi: 10.21203/rs.3.rs-5613372/v1.
RNA velocities and generalizations emerge as powerful approaches for extracting time-resolved information from high-throughput snapshot single-cell data. Yet, several inherent limitations restrict applying the approaches to genes not suitable for RNA velocity inference due to complex transcriptional dynamics, low expression, or lacking splicing dynamics, or data of non-transcriptomic modality. Here, we present GraphVelo, a graph-based machine learning procedure that uses as input the RNA velocities inferred from existing methods and infers velocity vectors lying in the tangent space of the low-dimensional manifold formed by the single cell data. GraphVelo preserves vector magnitude and direction information during transformations across different data representations. Tests on multiple synthetic and experimental scRNA-seq data including viral-host interactome and multi-omics datasets demonstrate that GraphVelo, together with downstream generalized dynamo analyses, extends RNA velocities to multi-modal data and reveals quantitative nonlinear regulation relations between genes, virus and host cells, and different layers of gene regulation.
RNA速度分析及其拓展方法已成为从高通量单细胞快照数据中提取时间分辨信息的有力手段。然而,由于复杂的转录动态、低表达或缺乏剪接动态,或者非转录组学模态的数据,一些固有的局限性限制了这些方法应用于不适合RNA速度推断的基因。在这里,我们提出了GraphVelo,这是一种基于图的机器学习方法,它以现有方法推断出的RNA速度作为输入,并推断位于单细胞数据形成的低维流形切空间中的速度向量。GraphVelo在跨不同数据表示的转换过程中保留向量大小和方向信息。对包括病毒-宿主相互作用组和多组学数据集在内的多个合成和实验性scRNA-seq数据的测试表明,GraphVelo与下游的广义动态分析一起,将RNA速度分析扩展到多模态数据,并揭示了基因、病毒和宿主细胞之间以及不同基因调控层之间的定量非线性调控关系。
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