Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos Building, Level 3, Singapore, 138648, Singapore.
Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Nat Commun. 2023 Mar 1;14(1):1155. doi: 10.1038/s41467-023-36796-3.
Spatial transcriptomics technologies generate gene expression profiles with spatial context, requiring spatially informed analysis tools for three key tasks, spatial clustering, multisample integration, and cell-type deconvolution. We present GraphST, a graph self-supervised contrastive learning method that fully exploits spatial transcriptomics data to outperform existing methods. It combines graph neural networks with self-supervised contrastive learning to learn informative and discriminative spot representations by minimizing the embedding distance between spatially adjacent spots and vice versa. We demonstrated GraphST on multiple tissue types and technology platforms. GraphST achieved 10% higher clustering accuracy and better delineated fine-grained tissue structures in brain and embryo tissues. GraphST is also the only method that can jointly analyze multiple tissue slices in vertical or horizontal integration while correcting batch effects. Lastly, GraphST demonstrated superior cell-type deconvolution to capture spatial niches like lymph node germinal centers and exhausted tumor infiltrating T cells in breast tumor tissue.
空间转录组学技术可提供具有空间背景的基因表达谱,需要具有空间信息分析工具来完成三个关键任务,即空间聚类、多样本整合和细胞类型去卷积。我们提出了 GraphST,这是一种基于图的自监督对比学习方法,可充分利用空间转录组学数据,从而优于现有方法。它将图神经网络与自监督对比学习相结合,通过最小化空间相邻点之间的嵌入距离和反之亦然,来学习信息丰富且具有区分度的点表示。我们在多种组织类型和技术平台上对 GraphST 进行了验证。GraphST 在大脑和胚胎组织中实现了 10%更高的聚类准确性和更好的精细组织结构描绘。GraphST 也是唯一一种能够在垂直或水平整合中同时分析多个组织切片并校正批次效应的方法。最后,GraphST 在乳腺癌组织中表现出优越的细胞类型去卷积能力,可捕获淋巴结生发中心和耗尽的肿瘤浸润 T 细胞等空间生态位。