Halmos Peter, Liu Xinhao, Gold Julian, Chen Feng, Ding Li, Raphael Benjamin J
Department of Computer Science, Princeton University, 35 Olden St, Princeton, NJ 08544.
Center for Statistics and Machine Learning, Princeton University, 26 Prospect Ave, Princeton, NJ 08544.
bioRxiv. 2024 Mar 10:2024.03.05.583575. doi: 10.1101/2024.03.05.583575.
Spatially resolved transcriptomics (SRT) measures mRNA transcripts at thousands of locations within a tissue slice, revealing spatial variations in gene expression and distribution of cell types. In recent studies, SRT has been applied to tissue slices from multiple timepoints during the development of an organism. Alignment of this transcriptomics data can provide insights into the gene expression programs governing the growth and differentiation of cells over space and time. We introduce DeST-OT (velopmental patioemporal ptimal ransport), a method to align SRT slices from pairs of developmental timepoints using the framework of optimal transport (OT). DeST-OT uses optimal transport to precisely model cellular growth, death, and differentiation processes that are not well-modeled by existing alignment methods. We demonstrate the advantage of DeST-OT on simulated slices. We further introduce two metrics to quantify the plausibility of a spatiotemporal alignment: a which quantifies the discrepancy between the inferred and the true cell type growth rates, and a which quantifies the distance traveled between ancestor and descendant cells. DeST-OT outperforms existing methods on these metrics in the alignment of spatiotemporal transcriptomics data from the development of axolotl brain.
空间分辨转录组学(SRT)可在组织切片内数千个位置测量mRNA转录本,揭示基因表达的空间变化以及细胞类型的分布。在最近的研究中,SRT已应用于生物体发育过程中多个时间点的组织切片。这种转录组学数据的比对能够为支配细胞在空间和时间上生长与分化的基因表达程序提供见解。我们引入了DeST-OT(发育时空最优传输),这是一种利用最优传输(OT)框架来比对来自发育时间点对的SRT切片的方法。DeST-OT使用最优传输来精确模拟现有比对方法难以很好模拟的细胞生长、死亡和分化过程。我们在模拟切片上展示了DeST-OT的优势。我们还引入了两个指标来量化时空比对的合理性:一个指标量化推断的和真实的细胞类型生长速率之间的差异,另一个指标量化祖先细胞和后代细胞之间的移动距离。在蝾螈脑发育的时空转录组学数据比对中,DeST-OT在这些指标上优于现有方法。