Zhang Pengzhi, Chen Weiqing, Tran Tu N, Zhou Minghao, Carter Kaylee N, Kandel Ibrahem, Li Shengyu, Hoi Xen Ping, Sun Yuxing, Lai Li, Youker Keith, Song Qianqian, Yang Yu, Nikolos Fotis, Li Zejuan, Chan Keith Syson, Cooke John P, Wang Guangyu
Center for Bioinformatics and Computational Biology, Houston Methodist Research Institute, Houston, TX, USA.
Center for RNA Therapeutics, Houston Methodist Research Institute, Houston, TX, USA.
Nat Commun. 2025 Aug 5;16(1):7178. doi: 10.1038/s41467-025-62593-1.
Spatial transcriptomics links gene expression with tissue morphology, however, current tools often prioritize genomic analysis, lacking integrated image interpretation. To address this, we present Thor, a comprehensive platform for cell-level analysis of spatial transcriptomics and histological images. Thor employs an anti-shrinking Markov diffusion method to infer single-cell spatial transcriptome from spot-level data, effectively combining gene expression and cell morphology. The platform includes 10 modular tools for genomic and image-based analysis, and is paired with Mjolnir, a web-based interface for interactive exploration of gigapixel images. Thor is validated on simulated data and multiple spatial platforms (ISH, MERFISH, Xenium, Stereo-seq). Thor characterizes regenerative signatures in heart failure, screens breast cancer hallmarks, resolves fine layers in mouse olfactory bulb, and annotates fibrotic heart tissue. In high-resolution Visium HD data, it enhances spatial gene patterns aligned with histology. By bridging transcriptomic and histological analysis, Thor enables holistic tissue interpretation in spatial biology.
空间转录组学将基因表达与组织形态学联系起来，然而，当前的工具往往优先进行基因组分析，缺乏综合的图像解读。为了解决这一问题，我们推出了Thor，这是一个用于空间转录组学和组织学图像细胞水平分析的综合平台。Thor采用抗收缩马尔可夫扩散方法从斑点水平数据推断单细胞空间转录组，有效地结合了基因表达和细胞形态。该平台包括10个用于基因组和基于图像分析的模块化工具，并与Mjolnir配对，Mjolnir是一个基于网络的界面，用于交互式探索千兆像素图像。Thor在模拟数据和多个空间平台（ISH、MERFISH、Xenium、Stereo-seq）上得到了验证。Thor表征了心力衰竭中的再生特征，筛选了乳腺癌标志物，解析了小鼠嗅球中的精细层，并对纤维化心脏组织进行了注释。在高分辨率的Visium HD数据中，它增强了与组织学对齐的空间基因模式。通过桥接转录组学和组织学分析，Thor实现了空间生物学中整体组织的解读。
