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.
Nat Commun. 2025 Aug 22;16(1):7831. doi: 10.1038/s41467-025-62784-w.
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 synthetic and experimental single-cell data, including viral-host interactome, multi-omics, and spatial genomics 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速度及相关推广方法成为从高通量快照单细胞数据中提取时间分辨信息的有力手段。然而,由于复杂的转录动力学、低表达、缺乏剪接动力学或非转录组学模态数据等原因,一些固有局限性限制了这些方法应用于不适合RNA速度推断的基因。在此,我们提出了GraphVelo,这是一种基于图的机器学习方法,它将现有方法推断出的RNA速度作为输入,并推断位于由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。对合成和实验单细胞数据的测试,包括病毒-宿主相互作用组、多组学和空间基因组学数据集,表明GraphVelo与下游广义动力学分析一起,将RNA速度扩展到多模态数据,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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