School of Computer Science and Engineering, Central South University, Changsha, Hunan 410083, China.
Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC), Chongqing University Three Gorges Hospital, Chongqing University, Chongqing 404031, China.
Brief Bioinform. 2023 Nov 22;25(1). doi: 10.1093/bib/bbad500.
With the development of spatially resolved transcriptomics technologies, it is now possible to explore the gene expression profiles of single cells while preserving their spatial context. Spatial clustering plays a key role in spatial transcriptome data analysis. In the past 2 years, several graph neural network-based methods have emerged, which significantly improved the accuracy of spatial clustering. However, accurately identifying the boundaries of spatial domains remains a challenging task. In this article, we propose stAA, an adversarial variational graph autoencoder, to identify spatial domain. stAA generates cell embedding by leveraging gene expression and spatial information using graph neural networks and enforces the distribution of cell embeddings to a prior distribution through Wasserstein distance. The adversarial training process can make cell embeddings better capture spatial domain information and more robust. Moreover, stAA incorporates global graph information into cell embeddings using labels generated by pre-clustering. Our experimental results show that stAA outperforms the state-of-the-art methods and achieves better clustering results across different profiling platforms and various resolutions. We also conducted numerous biological analyses and found that stAA can identify fine-grained structures in tissues, recognize different functional subtypes within tumors and accurately identify developmental trajectories.
随着空间分辨转录组学技术的发展,现在可以在保留细胞空间背景的情况下探索单细胞的基因表达谱。空间聚类在空间转录组数据分析中起着关键作用。在过去的 2 年中,出现了几种基于图神经网络的方法,这些方法显著提高了空间聚类的准确性。然而,准确识别空间域的边界仍然是一个具有挑战性的任务。在本文中,我们提出了 stAA,一种对抗变分图自动编码器,用于识别空间域。stAA 通过图神经网络利用基因表达和空间信息生成细胞嵌入,并通过 Wasserstein 距离强制细胞嵌入的分布服从先验分布。对抗训练过程可以使细胞嵌入更好地捕获空间域信息,更具鲁棒性。此外,stAA 使用通过预聚类生成的标签将全局图信息纳入细胞嵌入。我们的实验结果表明,stAA 优于最先进的方法,并在不同的分析平台和各种分辨率下实现了更好的聚类结果。我们还进行了大量的生物学分析,发现 stAA 可以识别组织中的精细结构,识别肿瘤内的不同功能亚型,并准确识别发育轨迹。