BGI Research, Beijing, 102601, China.
BGI Research, Shenzhen, 518083, China.
Nat Commun. 2024 Sep 6;15(1):7806. doi: 10.1038/s41467-024-51935-0.
Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, existing approaches overlook either spatial information or experiment-induced distortions, leading to significant discrepancies between reconstruction results and in vivo cell locations, causing unreliable downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS). By employing innovative Distributive Constraints into the Optimization scheme, ST-GEARS retrieves anchors with exceeding precision that connect closest spots across sections in vivo. Guided by the anchors, it first rigidly aligns sections, next solves and denoises Elastic Fields to counteract distortions. Through mathematically proved Bi-sectional Fields Application, it eventually recovers the original spatial profile. Studying ST-GEARS across number of sections, sectional distances and sequencing platforms, we observed its outstanding performance on tissue, cell, and gene levels. ST-GEARS provides precise and well-explainable 'gears' between in vivo situations and in vitro analysis, powerfully fueling potential of biological discoveries.
三维空间转录组学极大地推动了我们对组织分区、器官发生和发育的理解。然而，现有的方法要么忽略了空间信息，要么忽略了实验诱导的扭曲，导致重建结果与体内细胞位置之间存在显著差异，从而导致下游分析不可靠。为了解决这些挑战，我们提出了 ST-GEARS（通过 AnchoRS 进行空间转录组学的地理空间廓线恢复系统）。通过在优化方案中采用创新的分布式约束，ST-GEARS 以超过精度的方式恢复了连接体内切片中最近点的锚点。锚点的指导下，它首先刚性地对齐切片，然后解决并去噪弹性场以抵消扭曲。通过数学证明的双剖面场应用，它最终恢复了原始的空间廓线。通过对大量切片、切片距离和测序平台进行 ST-GEARS 研究，我们观察到它在组织、细胞和基因水平上的出色性能。ST-GEARS 在体内情况和体外分析之间提供了精确且可解释的“齿轮”，有力地推动了生物学发现的潜力。
