FICTURE: Scalable segmentation-free analysis of submicron resolution spatial transcriptomics.
FICTURE: Scalable segmentation-free analysis of submicron resolution spatial transcriptomics.
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图：亚微米分辨率空间转录组学的可扩展无分割分析。
DOI：
10.1101/2023.11.04.565621
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Kang,HyunMin
中科院分区：
文献类型：
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作者：
Si,Yichen;Lee,ChangHee;Hwang,Yongha;Yun,JeongH;Cheng,Weiqiu;Cho,Chun-Seok;Quiros,Miguel;Nusrat,Asma;Zhang,Weizhou;Jun,Goo;Zöllner,Sebastian;Lee,JunHee;Kang,HyunMin
空间转录组学（ST）技术已经发展到能够在大面积上以亚微米分辨率进行全转录组基因表达分析。然而，高分辨率ST的分析通常受到复杂组织结构的挑战，其中现有的细胞分割方法由于不规则的细胞大小和形状而难以实现，并且缺乏可扩展到全转录组分析的无分割方法。在这里，我们提出了FICTURE（超高分辨率下制图转录组的因子推断），这是一种无分割的空间因子分解方法，可以处理标记有数十亿亚微米分辨率空间坐标的转录组范围数据，并与基于测序和基于成像的ST数据兼容。FICTURE使用多层Dirichlet模型对像素级空间因子进行随机变分推断，比现有方法效率高出几个数量级。FICTURE揭示了具有挑战性的组织的微观ST结构，例如真实的数据中的血管、纤维化、肌肉和富含脂质的区域，而之前的方法都失败了。FICTURE的跨平台通用性、可扩展性和精确性使其成为探索高分辨率ST的强大工具。
Spatial transcriptomics (ST) technologies have advanced to enable transcriptome-wide gene expression analysis at submicron resolution over large areas. However, analysis of high-resolution ST is often challenged by complex tissue structure, where existing cell segmentation methods struggle due to the irregular cell sizes and shapes, and by the absence of segmentation-free methods scalable to whole-transcriptome analysis. Here we present FICTURE (Factor Inference of Cartographic Transcriptome at Ultra-high REsolution), a segmentation-free spatial factorization method that can handle transcriptome-wide data labeled with billions of submicron-resolution spatial coordinates and is compatible with both sequencing-based and imaging-based ST data. FICTURE uses the multilayered Dirichlet model for stochastic variational inference of pixel-level spatial factors, and is orders of magnitude more efficient than existing methods. FICTURE reveals the microscopic ST architecture for challenging tissues, such as vascular, fibrotic, muscular and lipid-laden areas in real data where previous methods failed. FICTURE’s cross-platform generality, scalability and precision make it a powerful tool for exploring high-resolution ST.