Dissecting Spatiotemporal Structures in Spatial Transcriptomics via Diffusion-Based Adversarial Learning.

Recent advancements in spatial transcriptomics (ST) technologies offer unprecedented opportunities to unveil the spatial heterogeneity of gene expression and cell states within tissues. Despite these capabilities of the ST data, accurately dissecting spatiotemporal structures (e.g., spatial domains, temporal trajectories, and functional interactions) remains challenging. Here, we introduce a computational framework, PearlST (partial differential equation [PDE]-enhanced adversarial graph autoencoder of ST), for accurate inference of spatiotemporal structures from the ST data using PDE-enhanced adversarial graph autoencoder. PearlST employs contrastive learning to extract histological image features, integrates a PDE-based diffusion model to enhance characterization of spatial features at domain boundaries, and learns the latent low-dimensional embeddings via Wasserstein adversarial regularized graph autoencoders. Comparative analyses across multiple ST datasets with varying resolutions demonstrate that PearlST outperforms existing methods in spatial clustering, trajectory inference, and pseudotime analysis. Furthermore, PearlST elucidates functional regulations of the latent features by linking intercellular ligand-receptor interactions to most contributing genes of the low-dimensional embeddings, as illustrated in a human breast cancer dataset. Overall, PearlST proves to be a powerful tool for extracting interpretable latent features and dissecting intricate spatiotemporal structures in ST data across various biological contexts.

Wang H ，Zhao J ，Nie Q ，Zheng C ，Sun X ... -  《Research》

stAA: adversarial graph autoencoder for spatial clustering task of spatially resolved transcriptomics.

Fang Z ，Liu T ，Zheng R ，A J ，Yin M ，Li M ... -  《-》

Spatially Informed Graph Structure Learning Extracts Insights from Spatial Transcriptomics.

Embeddings derived from cell graphs hold significant potential for exploring spatial transcriptomics (ST) datasets. Nevertheless, existing methodologies rely on a graph structure defined by spatial proximity, which inadequately represents the diversity inherent in cell-cell interactions (CCIs). This study introduces STAGUE, an innovative framework that concurrently learns a cell graph structure and a low-dimensional embedding from ST data. STAGUE employs graph structure learning to parameterize and refine a cell graph adjacency matrix, enabling the generation of learnable graph views for effective contrastive learning. The derived embeddings and cell graph improve spatial clustering accuracy and facilitate the discovery of novel CCIs. Experimental benchmarks across 86 real and simulated ST datasets show that STAGUE outperforms 15 comparison methods in clustering performance. Additionally, STAGUE delineates the heterogeneity in human breast cancer tissues, revealing the activation of epithelial-to-mesenchymal transition and PI3K/AKT signaling in specific sub-regions. Furthermore, STAGUE identifies CCIs with greater alignment to established biological knowledge than those ascertained by existing graph autoencoder-based methods. STAGUE also reveals the regulatory genes that participate in these CCIs, including those enriched in neuropeptide signaling and receptor tyrosine kinase signaling pathways, thereby providing insights into the underlying biological processes.

Nie W ，Yu Y ，Wang X ，Wang R ，Li SC ... -  《Advanced Science》

Identifying spatial domains of spatially resolved transcriptomics via multi-view graph convolutional networks.

Recent advances in spatially resolved transcriptomics (ST) technologies enable the measurement of gene expression profiles while preserving cellular spatial context. Linking gene expression of cells with their spatial distribution is essential for better understanding of tissue microenvironment and biological progress. However, effectively combining gene expression data with spatial information to identify spatial domains remains challenging. To deal with the above issue, in this paper, we propose a novel unsupervised learning framework named STMGCN for identifying spatial domains using multi-view graph convolution networks (MGCNs). Specifically, to fully exploit spatial information, we first construct multiple neighbor graphs (views) with different similarity measures based on the spatial coordinates. Then, STMGCN learns multiple view-specific embeddings by combining gene expressions with each neighbor graph through graph convolution networks. Finally, to capture the importance of different graphs, we further introduce an attention mechanism to adaptively fuse view-specific embeddings and thus derive the final spot embedding. STMGCN allows for the effective utilization of spatial context to enhance the expressive power of the latent embeddings with multiple graph convolutions. We apply STMGCN on two simulation datasets and five real spatial transcriptomics datasets with different resolutions across distinct platforms. The experimental results demonstrate that STMGCN obtains competitive results in spatial domain identification compared with five state-of-the-art methods, including spatial and non-spatial alternatives. Besides, STMGCN can detect spatially variable genes with enriched expression patterns in the identified domains. Overall, STMGCN is a powerful and efficient computational framework for identifying spatial domains in spatial transcriptomics data.

Shi X ，Zhu J ，Long Y ，Liang C ... -  《-》

Latent feature extraction with a prior-based self-attention framework for spatial transcriptomics.

Rapid advances in spatial transcriptomics (ST) have revolutionized the interrogation of spatial heterogeneity and increase the demand for comprehensive methods to effectively characterize spatial domains. As a prerequisite for ST data analysis, spatial domain characterization is a crucial step for downstream analyses and biological implications. Here we propose a prior-based self-attention framework for spatial transcriptomics (PAST), a variational graph convolutional autoencoder for ST, which effectively integrates prior information via a Bayesian neural network, captures spatial patterns via a self-attention mechanism, and enables scalable application via a ripple walk sampler strategy. Through comprehensive experiments on data sets generated by different technologies, we show that PAST can effectively characterize spatial domains and facilitate various downstream analyses, including ST visualization, spatial trajectory inference and pseudotime analysis. Also, we highlight the advantages of PAST for multislice joint embedding and automatic annotation of spatial domains in newly sequenced ST data. Compared with existing methods, PAST is the first ST method that integrates reference data to analyze ST data. We anticipate that PAST will open up new avenues for researchers to decipher ST data with customized reference data, which expands the applicability of ST technology.

Li Z ，Chen X ，Zhang X ，Jiang R ，Chen S ... -  《-》