Spatial-MGCN: a novel multi-view graph convolutional network for identifying spatial domains with attention mechanism.

Recent advances in spatial transcriptomics technologies have enabled gene expression profiles while preserving spatial context. Accurately identifying spatial domains is crucial for downstream analysis and it requires the effective integration of gene expression profiles and spatial information. While increasingly computational methods have been developed for spatial domain detection, most of them cannot adaptively learn the complex relationship between gene expression and spatial information, leading to sub-optimal performance. To overcome these challenges, we propose a novel deep learning method named Spatial-MGCN for identifying spatial domains, which is a Multi-view Graph Convolutional Network (GCN) with attention mechanism. We first construct two neighbor graphs using gene expression profiles and spatial information, respectively. Then, a multi-view GCN encoder is designed to extract unique embeddings from both the feature and spatial graphs, as well as their shared embeddings by combining both graphs. Finally, a zero-inflated negative binomial decoder is used to reconstruct the original expression matrix by capturing the global probability distribution of gene expression profiles. Moreover, Spatial-MGCN incorporates a spatial regularization constraint into the features learning to preserve spatial neighbor information in an end-to-end manner. The experimental results show that Spatial-MGCN outperforms state-of-the-art methods consistently in several tasks, including spatial clustering and trajectory inference.

Wang B ，Luo J ，Liu Y ，Shi W ，Xiong Z ，Shen C ，Long Y ... -  《-》

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 ... -  《-》

STGNNks: Identifying cell types in spatial transcriptomics data based on graph neural network, denoising auto-encoder, and k-sums clustering.

Spatial transcriptomics technologies fully utilize spatial location information, tissue morphological features, and transcriptional profiles. Integrating these data can greatly advance our understanding about cell biology in the morphological background. We developed an innovative spatial clustering method called STGNNks by combining graph neural network, denoising auto-encoder, and k-sums clustering. First, spatial resolved transcriptomics data are preprocessed and a hybrid adjacency matrix is constructed. Next, gene expressions and spatial context are integrated to learn spots' embedding features by a deep graph infomax-based graph convolutional network. Third, the learned features are mapped to a low-dimensional space through a zero-inflated negative binomial (ZINB)-based denoising auto-encoder. Fourth, a k-sums clustering algorithm is developed to identify spatial domains by combining k-means clustering and the ratio-cut clustering algorithms. Finally, it implements spatial trajectory inference, spatially variable gene identification, and differentially expressed gene detection based on the pseudo-space-time method on six 10x Genomics Visium datasets. We compared our proposed STGNNks method with five other spatial clustering methods, CCST, Seurat, stLearn, Scanpy and SEDR. For the first time, four internal indicators in the area of machine learning, that is, silhouette coefficient, the Davies-Bouldin index, the Caliniski-Harabasz index, and the S_Dbw index, were used to measure the clustering performance of STGNNks with CCST, Seurat, stLearn, Scanpy and SEDR on five spatial transcriptomics datasets without labels (i.e., Adult Mouse Brain (FFPE), Adult Mouse Kidney (FFPE), Human Breast Cancer (Block A Section 2), Human Breast Cancer (FFPE), and Human Lymph Node). And two external indicators including adjusted Rand index (ARI) and normalized mutual information (NMI) were applied to evaluate the performance of the above six methods on Human Breast Cancer (Block A Section 1) with real labels. The comparison experiments elucidated that STGNNks obtained the smallest Davies-Bouldin and S_Dbw values and the largest Silhouette Coefficient, Caliniski-Harabasz, ARI and NMI, significantly outperforming the above five spatial transcriptomics analysis algorithms. Furthermore, we detected the top six spatially variable genes and the top five differentially expressed genes in each cluster on the above five unlabeled datasets. And the pseudo-space-time tree plot with hierarchical layout demonstrated a flow of Human Breast Cancer (Block A Section 1) progress in three clades branching from three invasive ductal carcinoma regions to multiple ductal carcinoma in situ sub-clusters. We anticipate that STGNNks can efficiently improve spatial transcriptomics data analysis and further boost the diagnosis and therapy of related diseases. The codes are publicly available at https://github.com/plhhnu/STGNNks.

Peng L ，He X ，Peng X ，Li Z ，Zhang L ... -  《-》

MAMF-GCN: Multi-scale adaptive multi-channel fusion deep graph convolutional network for predicting mental disorder.

Existing diagnoses of mental disorders rely on symptoms, patient descriptions, and scales, which are not objective enough. We attempt to explore an objective diagnostic method on fMRI data. Graph neural networks (GNN) have been paid more attention recently because of their advantages in processing unstructured relational data, especially for fMRI data. However, how to deeply embed and well-integrate with different modalities and scales on GNN is still a challenge. Instead of reaching a high degree of fusion, existing GCN methods simply combine image and non-image data. Most graph convolutional network (GCN) models use shallow structures, making it challenging to learn about potential information. Furthermore, current graph construction approaches usually use a single specific brain atlas, limiting the analysis and results. In this paper, a multi-scale adaptive multi-channel fusion deep graph convolutional network based on an attention mechanism (MAMF-GCN) is proposed to better integrate features of modalities and different atlas by exploiting multi-channel correlation. An encoder automatically combines one channel with non-imaging data to generate similarity weights between subjects using a similarity perception mechanism. Other channels generate multi-scale imaging features of fMRI data after processing in the different atlas. Multi-modal information is fused using an adaptive convolution module that applies a deep graph convolutional network (GCN) to extract information from richer hidden layers. To demonstrate the effectiveness of our approach, we evaluate the performance of the proposed method on the Autism Brain Imaging Data Exchange (ABIDE) dataset and the Major Depressive Disorder (MDD) dataset. The experimental result shows that the proposed method outperforms many state-of-the-art methods in node classification performance. An extensive group of experiments on two disease prediction tasks demonstrates that the performance of the proposed MAMF-GCN on MDD/ABIDE dataset is improved by 3.37%-39.83% and 12.59%-32.92%, respectively. Moreover, our proposed method has also shown very effective performance in real-life clinical diagnosis. The comprehensive experiments demonstrate that our method is effective for node classification with brain disorders diagnosis. The proposed MAMF-GCN method simultaneously extracts specific and common embeddings from the topology composed of multi-scale imaging features, phenotypic information, and their combinations, then learning adaptive embedding weights by attention mechanism, which can capture and fuse the multi-scale essential embeddings to improve the classification performance of brain disorder diagnosis.

Pan J ，Lin H ，Dong Y ，Wang Y ，Ji Y ... -  《-》

Integrating multi-modal information to detect spatial domains of spatial transcriptomics by graph attention network.

Recent advances in spatially resolved transcriptomic technologies have enabled unprecedented opportunities to elucidate tissue architecture and function in situ. Spatial transcriptomics can provide multimodal and complementary information simultaneously, including gene expression profiles, spatial locations, and histology images. However, most existing methods have limitations in efficiently utilizing spatial information and matched high-resolution histology images. To fully leverage the multi-modal information, we propose a SPAtially embedded Deep Attentional graph Clustering (SpaDAC) method to identify spatial domains while reconstructing denoised gene expression profiles. This method can efficiently learn the low-dimensional embeddings for spatial transcriptomics data by constructing multi-view graph modules to capture both spatial location connectives and morphological connectives. Benchmark results demonstrate that SpaDAC outperforms other algorithms on several recent spatial transcriptomics datasets. SpaDAC is a valuable tool for spatial domain detection, facilitating the comprehension of tissue architecture and cellular microenvironment. The source code of SpaDAC is freely available at Github (https://github.com/huoyuying/SpaDAC.git).

Huo Y ，Guo Y ，Wang J ，Xue H ，Feng Y ，Chen W ，Li X ... -  《Journal of Genetics and Genomics》