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》

CLARIFY: cell-cell interaction and gene regulatory network refinement from spatially resolved transcriptomics.

Bafna M ，Li H ，Zhang X 《-》

Accurate Spatial Heterogeneity Dissection and Gene Regulation Interpretation for Spatial Transcriptomics using Dual Graph Contrastive Learning.

Recent advances in spatial transcriptomics have enabled simultaneous preservation of high-throughput gene expression profiles and the spatial context, enabling high-resolution exploration of distinct regional characterization in tissue. To effectively understand the underlying biological mechanisms within tissue microenvironments, there is a requisite for methods that can accurately capture external spatial heterogeneity and interpret internal gene regulation from spatial transcriptomics data. However, current methods for region identification often lack the simultaneous characterizing of spatial structure and gene regulation, thereby limiting the ability of spatial dissection and gene interpretation. Here, stDCL is developed, a dual graph contrastive learning method to identify spatial domains and interpret gene regulation in spatial transcriptomics data. stDCL adaptively incorporates gene expression data and spatial information via a graph embedding autoencoder, thereby preserving critical information within the latent embedding representations. In addition, dual graph contrastive learning is proposed to train the model, ensuring that the latent embedding representation closely resembles the actual spatial distribution and exhibits cluster similarity. Benchmarking stDCL against other state-of-the-art clustering methods using complex cortex datasets demonstrates its superior accuracy and effectiveness in identifying spatial domains. Our analysis of the imputation matrices generated by stDCL reveals its capability to reconstruct spatial hierarchical structures and refine differential expression assessment. Furthermore, it is demonstrated that the versatility of stDCL in interpretability of gene regulation, spatial heterogeneity at high resolution, and embryonic developmental patterns. In addition, it is also showed that stDCL can successfully annotate disease-associated astrocyte subtypes in Alzheimer's disease and unravel multiple relevant pathways and regulatory mechanisms.

Yu Z ，Yang Y ，Chen X ，Wong KC ，Zhang Z ，Zhao Y ，Li X ... -  《Advanced Science》

Edge-Centric Embeddings of Digraphs: Properties and Stability Under Sparsification.

Begga A ，Escolano Ruiz F ，Lozano MÁ 《Entropy》

Unveiling patterns in spatial transcriptomics data: a novel approach utilizing graph attention autoencoder and multiscale deep subspace clustering network.

The accurate deciphering of spatial domains, along with the identification of differentially expressed genes and the inference of cellular trajectory based on spatial transcriptomic (ST) data, holds significant potential for enhancing our understanding of tissue organization and biological functions. However, most of spatial clustering methods can neither decipher complex structures in ST data nor entirely employ features embedded in different layers. This article introduces STMSGAL, a novel framework for analyzing ST data by incorporating graph attention autoencoder and multiscale deep subspace clustering. First, STMSGAL constructs ctaSNN, a cell type-aware shared nearest neighbor graph, using Louvian clustering exclusively based on gene expression profiles. Subsequently, it integrates expression profiles and ctaSNN to generate spot latent representations using a graph attention autoencoder and multiscale deep subspace clustering. Lastly, STMSGAL implements spatial clustering, differential expression analysis, and trajectory inference, providing comprehensive capabilities for thorough data exploration and interpretation. STMSGAL was evaluated against 7 methods, including SCANPY, SEDR, CCST, DeepST, GraphST, STAGATE, and SiGra, using four 10x Genomics Visium datasets, 1 mouse visual cortex STARmap dataset, and 2 Stereo-seq mouse embryo datasets. The comparison showcased STMSGAL's remarkable performance across Davies-Bouldin, Calinski-Harabasz, S_Dbw, and ARI values. STMSGAL significantly enhanced the identification of layer structures across ST data with different spatial resolutions and accurately delineated spatial domains in 2 breast cancer tissues, adult mouse brain (FFPE), and mouse embryos. STMSGAL can serve as an essential tool for bridging the analysis of cellular spatial organization and disease pathology, offering valuable insights for researchers in the field.

Zhou L ，Peng X ，Chen M ，He X ，Tian G ，Yang J ，Peng L ... -  《GigaScience》