Advances in spatial omics technologies now allow multiple types of data to be acquired from the same tissue slice. To realize the full potential of such data, we need spatially informed methods for data integration. Here, we introduce SpatialGlue, a graph neural network model with a dual-attention mechanism that deciphers spatial domains by intra-omics integration of spatial location and omics measurement followed by cross-omics integration. We demonstrated SpatialGlue on data acquired from different tissue types using different technologies, including spatial epigenome–transcriptome and transcriptome–proteome modalities. Compared to other methods, SpatialGlue captured more anatomical details and more accurately resolved spatial domains such as the cortex layers of the brain. Our method also identified cell types like spleen macrophage subsets located at three different zones that were not available in the original data annotations. SpatialGlue scales well with data size and can be used to integrate three modalities. Our spatial multi-omics analysis tool combines the information from complementary omics modalities to obtain a holistic view of cellular and tissue properties.

Accumulating clinic evidences have demonstrated that the microbes residing in human bodies play a significantly important role in the formation, development and progression of various complex human diseases. Indentifying latent related microbes for disease could provide insight into human disease mechanisms and promote disease prevention, diagnosis and treatment. In this paper, we first construct a heterogeneous network by connecting the disease similarity network and the microbe similarity network through known microbe-disease association network, and then develop a novel computational model to predict human microbe-disease associations based on random walk by integrating network topological similarity (NTSHMDA). Specifically, each microbe-disease association pair is regarded as distinct relationship level and, thus, assigned different weights based on network topological similarity. The experimental results show that NTSHMDA outperforms some state-of-the-art methods with average AUCs of 0.9070, in the frameworks of Leave-one-out cross validation and 5-fold cross validation, respectively. In case studies, 9, 18, 38 and 9, 18, 45 out of top-10, 20, 50 candidate microbes are verified by recently published literatures for asthma and inflammatory bowel disease, respectively. In conclusion, NTSHMDA has potential ability to identify novel disease-microbe associations and can also provide valuable information for drug discovery and biological researches.

Graphs or networks are widely utilized to model the interactions between different entities (e.g. proteins, drugs, etc.) for biomedical applications. Predicting potential interactions/links in biomedical networks is important for understanding the pathological mechanisms of various complex human diseases, as well as screening compound targets for drug discovery. Graph neural networks (GNNs) have been utilized for link prediction in various biomedical networks, which rely on the node features extracted from different data sources, e.g. sequence, structure and network data. However, it is challenging to effectively integrate these data sources and automatically extract features for different link prediction tasks. In this article, we propose a novel Pre-Training Graph Neural Networks-based framework named PT-GNN to integrate different data sources for link prediction in biomedical networks. First, we design expressive deep learning methods [e.g. convolutional neural network and graph convolutional network (GCN)] to learn features for individual nodes from sequence and structure data. Second, we further propose a GCN-based encoder to effectively refine the node features by modelling the dependencies among nodes in the network. Third, the node features are pre-trained based on graph reconstruction tasks. The pre-trained features can be used for model initialization in downstream tasks. Extensive experiments have been conducted on two critical link prediction tasks, i.e. synthetic lethality (SL) prediction and drug–target interaction (DTI) prediction. Experimental results demonstrate PT-GNN outperforms the state-of-the-art methods for SL prediction and DTI prediction. In addition, the pre-trained features benefit improving the performance and reduce the training time of existing models. Python codes and dataset are available at: https://github.com/longyahui/PT-GNN. Supplementary data are available at Bioinformatics online.

Accurately identifying microbe-drug associations plays a critical role in drug development and precision medicine. Considering that the conventional wet-lab method is timeconsuming, labor-intensive and expensive, computational approach is an alternative choice. The increasing availability of numerous biological data provides a great opportunity to systematically understand complex interaction mechanisms between microbes and drugs. However, few computational methods have been developed for microbe drug prediction. In this work, we leverage multiple sources of biomedical data to construct a heterogeneous network for microbes and drugs, including drugdrug interactions, microbe-microbe interactions and microbedrug associations. And then we propose a novel Heterogeneous Network Embedding Representation framework for Microbe- Drug Association prediction, named (HNERMDA), by combining metapath2vec with bipartite network recommendation. In this framework, we introduce metapath2vec, a heterogeneous network representation learning method, to learn low-dimensional embedding representations for microbes and drugs. Following that, we further design a bias bipartite network projection recommendation algorithm to improve prediction accuracy. Comprehensive experiments on two datasets, named MDAD and aBiofilm, demonstrated that our model consistently outperformed five baseline methods in three types of cross-validations. Case study on two popular drugs (i.e., Ciprofloxacin and Pefloxacin) further validated the effectiveness of our HNERMDA model in inferring potential target microbes for drugs.

Synthetic lethality (SL) is a gold mine of anticancer drug targets, exposing cancer-specific dependencies of cellular survival. To complement resource-intensive experimental screening, many machine learning methods for SL prediction have emerged recently. However, a comprehensive benchmarking is lacking. This study systematically benchmarks 12 recent machine learning methods for SL prediction, assessing their performance across diverse data splitting scenarios, negative sample ratios, and negative sampling techniques, on both classification and ranking tasks. We observe that all the methods can perform significantly better by improving data quality, e.g., excluding computationally derived SLs from training and sampling negative labels based on gene expression. Among the methods, SLMGAE performs the best. Furthermore, the methods have limitations in realistic scenarios such as cold-start independent tests and context-specific SLs. These results, together with source code and datasets made freely available, provide guidance for selecting suitable methods and developing more powerful techniques for SL virtual screening.

EzSingleCell is an interactive and easy-to-use application for analysing various single-cell and spatial omics data types without requiring prior programing knowledge. It combines the best-performing publicly available methods for in-depth data analysis, integration, and interactive data visualization. ezSingleCell consists of five modules, each designed to be a comprehensive workflow for one data type or task. In addition, ezSingleCell allows crosstalk between different modules within a unified interface. Acceptable input data can be in a variety of formats while the output consists of publication ready figures and tables. In-depth manuals and video tutorials are available to guide users on the analysis workflows and parameter adjustments to suit their study aims. ezSingleCell’s streamlined interface can analyse a standard scRNA-seq dataset of 3000 cells in less than five minutes. ezSingleCell is available in two forms: an installation-free web application (https://immunesinglecell.org/ezsc/) or a software package with a shinyApp interface (https://github.com/JinmiaoChenLab/ezSingleCell2) for offline analysis.