Abstract：
Cell-type-specific domains are the anatomical domains in spatially resolved transcriptome (SRT) tissues where particular cell types are enriched coincidentally. It is challenging to use existing computational methods to detect specific domains with low-proportion cell types, which are partly overlapped with or even inside other cell-type-specific domains. Here, we propose De-spot, which synthesizes segmentation and deconvolution as an ensemble to generate cell-type patterns, detect low-proportion cell-type-specific domains, and display these domains intuitively. Experimental evaluation showed that De-spot enabled us to discover the co-localizations between cancer-associated fibroblasts and immune-related cells that indicate potential tumor microenvironment (TME) domains in given slices, which were obscured by previous computational methods. We further elucidated the identified domains and found that Srgn may be a critical TME marker in SRT slices. By deciphering T cell-specific domains in breast cancer tissues, De-spot also revealed that the proportions of exhausted T cells were significantly increased in invasive vs. ductal carcinoma.
摘要：
细胞类型特异性结构域是空间分辨转录组（SRT）组织中的解剖结构域，其中特定细胞类型同时富集。使用现有的计算方法来检测具有低比例细胞类型的特定域是具有挑战性的，与其他细胞类型特异性结构域部分重叠或甚至在内部。这里,我们建议去现场，它将分割和反卷积合成为一个集合来生成细胞类型的模式，检测低比例的细胞类型特异性结构域，并直观地显示这些领域。实验评估表明，De-spot使我们能够发现癌症相关成纤维细胞和免疫相关细胞之间的共定位，这表明给定切片中潜在的肿瘤微环境（TME）域，被以前的计算方法掩盖了。我们进一步阐明了鉴定的结构域，发现Srgn可能是SRT切片中的关键TME标记。通过破译乳腺癌组织中的T细胞特异性结构域，De-spot还显示，耗竭T细胞的比例在侵袭性与侵袭性之间显着增加。导管癌.
