Graph neural networks (GNNs), as a branch of deep learning in non-Euclidean space, perform particularly well in various tasks that process graph structure data. With the rapid accumulation of biological network data, GNNs have also become an important tool in bioinformatics. In this research, a systematic survey of GNNs and their advances in bioinformatics is presented from multiple perspectives. We first introduce some commonly used GNN models and their basic principles. Then, three representative tasks are proposed based on the three levels of structural information that can be learned by GNNs: node classification, link prediction, and graph generation. Meanwhile, according to the specific applications for various omics data, we categorize and discuss the related studies in three aspects: disease prediction, drug discovery, and biomedical imaging. Based on the analysis, we provide an outlook on the shortcomings of current studies and point out their developing prospect. Although GNNs have achieved excellent results in many biological tasks at present, they still face challenges in terms of low-quality data processing, methodology, and interpretability and have a long road ahead. We believe that GNNs are potentially an excellent method that solves various biological problems in bioinformatics research.

A large number (n = 460) of A(H7N9) human infections have been reported in China from March 2013 through December 2014, and H7N9 outbreaks in humans became an emerging issue for China health, which have caused numerous disease outbreaks in domestic poultry and wild bird populations, and threatened human health severely. The aims of this study were to investigate the directional trend of the epidemic and to identify the significant presence of spatial-temporal clustering of influenza A(H7N9) human cases between March 2013 and December 2014. Three distinct epidemic phases of A(H7N9) human infections were identified in this study. In each phase, standard deviational ellipse analysis was conducted to examine the directional trend of disease spreading, and retrospective space-time permutation scan statistic was then used to identify the spatio-temporal cluster patterns of H7N9 outbreaks in humans. The ever-changing location and the increasing size of the three identified standard deviational ellipses showed that the epidemic moved from east to southeast coast, and hence to some central regions, with a future epidemiological trend of continue dispersing to more central regions of China, and a few new human cases might also appear in parts of the western China. Furthermore, A(H7N9) human infections were clustering in space and time in the first two phases with five significant spatio-temporal clusters (p < 0.05), but there was no significant cluster identified in phase III. There was a new epidemiologic pattern that the decrease in significant spatio-temporal cluster of A(H7N9) human infections was accompanied with an obvious spatial expansion of the outbreaks during the study period, and identification of the spatio-temporal patterns of the epidemic can provide valuable insights for better understanding the spreading dynamics of the disease in China.

In recent years, a large number of studies have shown that the subcellular localization of long non-coding RNAs (lncRNAs) can bring crucial information to the recognition of lncRNAs function. Therefore, it is of great significance to establish a computational method to accurately predict the subcellular localization of lncRNA. Previous prediction models are based on low-level sequences information and are troubled by the few samples problem. In this study, we propose a new prediction model, GM-lncLoc, which is based on the initial information extracted from the lncRNA sequence, and also combines the graph structure information to extract high level features of lncRNA. In addition, the training mode of meta-learning is introduced to obtain meta-parameters by training a series of tasks. With the meta-parameters, the final parameters of other similar tasks can be learned quickly, so as to solve the problem of few samples in lncRNA subcellular localization. Compared with the previous methods, GM-lncLoc achieved the best results with an accuracy of 93.4 and 94.2% in the benchmark datasets of 5 and 4 subcellular compartments, respectively. Furthermore, the prediction performance of GM-lncLoc was also better on the independent dataset. It shows the effectiveness and great potential of our proposed method for lncRNA subcellular localization prediction. The datasets and source code are freely available athttps://github.com/JunzheCai/GM-lncLoc.

Identifying lncRNA-disease associations is conducive to the diagnosis, treatment and prevention of diseases. Due to the expensive and time-consuming methods verified by biological experiments, prediction methods based on computational models have gradually become an important means of lncRNA-disease associations discovery. However, existing methods still have challenges to make full use of network topology information to identify potential associations between lncRNA and disease in multi-source data. In this study, we propose a novel method called HGNNLDA for lncRNA-disease association prediction. First, HGNNLDA constructs a heterogeneous network composed of lncRNA similarity network, lncRNA-disease association network and lncRNA-miRNA association network; Then, on this heterogeneous network, various types of strong correlation neighbors with fixed size are sampled for each node by restart random walk; Next, the embedding information of lncRNA and disease in each lncRNA-disease association pair is obtained by the method of type-based neighbor aggregation and all types combination though heterogeneous graph neural network, in which attention mechanism is introduced considering that different types of neighbors will make different contributions to the prediction of lncRNA-disease association. As a result, the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPR) under fivefold cross-validation (5FCV) are 0.9786 and 0.8891, respectively. Compared with five state-of-art prediction models, HGNNLDA has better prediction performance. In addition, in two types of case studies, it is further verified that our method can effectively predict the potential lncRNA-disease associations, and have ability to predict new diseases without any known lncRNAs.

There is a growing body of evidence indicating the crucial roles that long non-coding RNAs (lncRNAs) play in the development and progression of various diseases, including cancers, cardiovascular diseases, and neurological disorders. However, accurately predicting potential lncRNA-disease associations remains a challenge, as existing methods have limitations in extracting heterogeneous association information and handling sparse and unbalanced data. To address these issues, we propose a novel computational method, called HGC-GAN, which combines heterogeneous graph convolutional neural networks (GCN) and generative adversarial networks (GAN) to predict potential lncRNA-disease associations. Specifically, we construct a lncRNA-miRNA-disease heterogeneous network by integrating multiple association data and sequence information. The GCN-based generator is then employed to aggregate neighbor information of nodes and obtain node embeddings, which are used to predict lncRNA-disease associations. Meanwhile, the GAN-based discriminator is trained to distinguish between real and fake lncRNA-disease associations generated by the generator, enabling the generator to improve its ability to generate accurate lncRNA-disease associations gradually. Our experimental results demonstrate that HGC-GAN performs better in predicting potential lncRNA-disease associations, with AUC and AUPR values of 0.9591 and 0.9606, respectively, under 10-fold cross-validation. Moreover, our case study further confirms the effectiveness of HGC-GAN in predicting potential lncRNA-disease associations, even for novel lncRNAs without any known lncRNA-disease associations. Overall, our proposed method HGC-GAN provides a promising approach to predict potential lncRNA-disease associations and may have important implications for disease diagnosis, treatment, and drug development.