Systematic benchmarking of high-throughput subcellular spatial transcriptomics platforms across human tumors.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-17 DOI:10.1038/s41467-025-64292-3

Pengfei Ren, Rui Zhang, Yunfeng Wang, Peng Zhang, Ce Luo, Suyan Wang, Xiaohong Li, Zongxu Zhang, Yanping Zhao, Yufeng He, Haorui Zhang, Yufeng Li, Zhidong Gao, Xiuping Zhang, Yahui Zhao, Zhihua Liu, Yuanguang Meng, Zhe Zhang, Zexian Zeng

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引用次数: 0

Abstract

Recent advancements in spatial transcriptomics technologies have significantly enhanced resolution and throughput, underscoring an urgent need for systematic benchmarking. Here, we generate serial tissue sections from colon adenocarcinoma, hepatocellular carcinoma, and ovarian cancer samples for systematic evaluation. Using these uniformly processed samples, we generate spatial transcriptomics data across four high-throughput platforms with subcellular resolution: Stereo-seq v1.3, Visium HD FFPE, CosMx 6K, and Xenium 5K. To establish ground truth datasets, we profile proteins on tissue sections adjacent to all platforms using CODEX and perform single-cell RNA sequencing on the same samples. Leveraging manual nuclear segmentation and detailed annotations, we systematically assess each platform's performance across capture sensitivity, specificity, diffusion control, cell segmentation, cell annotation, spatial clustering, and concordance with adjacent CODEX. The uniformly generated and processed multi-omics dataset could advance computational method development and biological discoveries. The dataset is accessible via SPATCH, a user-friendly web server for visualization and download.

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跨人类肿瘤的高通量亚细胞空间转录组学平台的系统基准。

空间转录组学技术的最新进展显著提高了分辨率和通量，强调了系统基准测试的迫切需要。在这里，我们从结肠腺癌、肝细胞癌和卵巢癌样本中生成一系列组织切片，用于系统评估。使用这些均匀处理的样本，我们在四个高通量平台上生成空间转录组学数据，具有亚细胞分辨率：Stereo-seq v1.3, Visium HD FFPE， CosMx 6K和Xenium 5K。为了建立真实数据集，我们使用CODEX分析所有平台附近组织切片上的蛋白质，并对相同样品进行单细胞RNA测序。利用人工核分割和详细注释，我们系统地评估了每个平台的性能，包括捕获灵敏度、特异性、扩散控制、细胞分割、细胞注释、空间聚类以及与相邻CODEX的一致性。统一生成和处理的多组学数据集可以促进计算方法的发展和生物学的发现。数据集可以通过SPATCH访问，SPATCH是一个用户友好的web服务器，用于可视化和下载。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.