Department of Mathematics, University of California, Irvine, Irvine, CA, USA.
Center for Machine Learning Research, Peking University, Beijing, China.
Nat Methods. 2024 Jun;21(6):1053-1062. doi: 10.1038/s41592-024-02266-x. Epub 2024 May 16.
Spatial transcriptomics and messenger RNA splicing encode extensive spatiotemporal information for cell states and transitions. The current lineage-inference methods either lack spatial dynamics for state transition or cannot capture different dynamics associated with multiple cell states and transition paths. Here we present spatial transition tensor (STT), a method that uses messenger RNA splicing and spatial transcriptomes through a multiscale dynamical model to characterize multistability in space. By learning a four-dimensional transition tensor and spatial-constrained random walk, STT reconstructs cell-state-specific dynamics and spatial state transitions via both short-time local tensor streamlines between cells and long-time transition paths among attractors. Benchmarking and applications of STT on several transcriptome datasets via multiple technologies on epithelial-mesenchymal transitions, blood development, spatially resolved mouse brain and chicken heart development, indicate STT's capability in recovering cell-state-specific dynamics and their associated genes not seen using existing methods. Overall, STT provides a consistent multiscale description of single-cell transcriptome data across multiple spatiotemporal scales.
空间转录组学和信使 RNA 剪接为细胞状态和转变提供了丰富的时空信息。目前的谱系推断方法要么缺乏状态转变的空间动态,要么无法捕捉与多个细胞状态和转变路径相关的不同动态。在这里,我们提出了空间转变张量(STT),这是一种通过多尺度动力学模型利用信使 RNA 剪接和空间转录组学来描述空间多稳定性的方法。通过学习一个四维转变张量和空间约束的随机游走,STT 通过细胞间的短时间局部张量流线和吸引子之间的长时间转变路径,重建细胞状态特异性动力学和空间状态转变。通过多种技术在上皮-间充质转变、血液发育、空间解析的小鼠大脑和鸡心脏发育等几个转录组数据集上对 STT 的基准测试和应用表明,STT 能够恢复使用现有方法无法看到的细胞状态特异性动力学及其相关基因。总的来说,STT 为单细胞转录组数据在多个时空尺度上提供了一致的多尺度描述。