The gene regulatory network (GRN) plays a vital role in understanding the structure and dynamics of cellular systems, revealing complex regulatory relationships, and exploring disease mechanisms. Recently, deep learning (DL)–based methods have been proposed to infer GRNs from single-cell transcriptomic data and achieved impressive performance. However, these methods do not fully utilize graph topological information and high-order neighbor information from multiple receptive fields. To overcome those limitations, we propose a novel model based on multiview graph attention network, namely, scMGATGRN, to infer GRNs. scMGATGRN mainly consists of GAT, multiview, and view-level attention mechanism. GAT can extract essential features of the gene regulatory network. The multiview model can simultaneously utilize local feature information and high-order neighbor feature information of nodes in the gene regulatory network. The view-level attention mechanism dynamically adjusts the relative importance of node embedding representations and efficiently aggregates node embedding representations from two views. To verify the effectiveness of scMGATGRN, we compared its performance with 10 methods (five shallow learning algorithms and five state-of-the-art DL-based methods) on seven benchmark single-cell RNA sequencing (scRNA-seq) datasets from five cell lines (two in human and three in mouse) with four different kinds of ground-truth networks. The experimental results not only show that scMGATGRN outperforms competing methods but also demonstrate the potential of this model in inferring GRNs. The code and data of scMGATGRN are made freely available on GitHub (https://github.com/nathanyl/scMGATGRN).

Underlying a cancer phenotype is a specific gene regulatory network that represents the complex regulatory relationships between genes. It remains, however, a challenge to find cancer-related gene regulatory network because of insufficient sample sizes and complex regulatory mechanisms in which gene is influenced by not only other genes but also other biological factors. With the development of high-throughput technologies and the unprecedented wealth of multi-omics data it gives us a new opportunity to design machine learning method to investigate underlying gene regulatory network. In this paper, we propose an approach, which use Biweight Midcorrelation to measure the correlation between factors and make use of Nonconvex Penalty based sparse regression for Gene Regulatory Network inference (BMNPGRN). BMNCGRN incorporates multi-omics data (including DNA methylation and copy number variation) and their interactions in gene regulatory network model. The experimental results on synthetic datasets show that BMNPGRN outperforms popular and state-of-the-art methods (including DCGRN, ARACNE, and CLR) under false positive control. Furthermore, we applied BMNPGRN on breast cancer (BRCA) data from The Cancer Genome Atlas database and provided gene regulatory network.

Cell type annotation is a critical step in analyzing single-cell RNA sequencing (scRNA-seq) data. A large number of deep learning (DL)–based methods have been proposed to annotate cell types of scRNA-seq data and have achieved impressive results. However, there are several limitations to these methods. First, they do not fully exploit cell-to-cell differential features. Second, they are developed based on shallow features and lack of flexibility in integrating high-order features in the data. Finally, the low-dimensional gene features may lead to overfitting in neural networks. To overcome those limitations, we propose a novel DL-based model, cell type annotation of single-cell RNA-seq data using residual graph convolutional neural network with contrastive learning (scRGCL), based on residual graph convolutional neural network and contrastive learning for cell type annotation of single-cell RNA-seq data. scRGCL mainly consists of a residual graph convolutional neural network, contrastive learning, and weight freezing. A residual graph convolutional neural network is utilized to extract complex high-order features from data. Contrastive learning can help the model learn meaningful cell-to-cell differential features. Weight freezing can avoid overfitting and help the model discover the impact of specific gene expression on cell type annotation. To verify the effectiveness of scRGCL, we compared its performance with six methods (three shallow learning algorithms and three state-of-the-art DL-based methods) on eight single-cell benchmark datasets from two species (seven in human and one in mouse). Experimental results not only show that scRGCL outperforms competing methods but also demonstrate the generalizability of scRGCL for cell type annotation. scRGCL is available at https://github.com/nathanyl/scRGCL.

Background: LncRNAs (Long non-coding RNAs) are a type of non-coding RNA molecule with transcript length longer than 200 nucleotides. LncRNA has been novel candidate biomarkers in cancer diagnosis and prognosis. However, it is difficult to discover the true association mechanism between lncRNAs and complex diseases. The unprecedented enrichment of multi-omics data and the rapid development of machine learning technology provide us with the opportunity to design a machine learning framework to study the relationship between lncRNAs and complex diseases. Results: In this article, we proposed a new machine learning approach, namely LGDLDA (LncRNA-Gene-Disease association networks based LncRNA-Disease Association prediction), for disease-related lncRNAs association prediction based multi-omics data, machine learning methods and neural network neighborhood information aggregation. Firstly, LGDLDA calculates the similarity matrix of lncRNA, gene and disease respectively, and it calculates the similarity between lncRNAs through the lncRNA expression profile matrix, lncRNA-miRNA interaction matrix and lncRNA-protein interaction matrix. We obtain gene similarity matrix by calculating the lncRNA-gene association matrix and the gene-disease association matrix, and we obtain disease similarity matrix by calculating the disease ontology, the disease-miRNA association matrix, and Gaussian interaction profile kernel similarity. Secondly, LGDLDA integrates the neighborhood information in similarity matrices by using nonlinear feature learning of neural network. Thirdly, LGDLDA uses embedded node representations to approximate the observed matrices. Finally, LGDLDA ranks candidate lncRNA-disease pairs and then selects potential disease-related lncRNAs. Conclusions: Compared with lncRNA-disease prediction methods, our proposed method takes into account more critical information and obtains the performance improvement cancer-related lncRNA predictions. Randomly split data experiment results show that the stability of LGDLDA is better than IDHI-MIRW, NCPLDA, LncDisAP and NCPHLDA. The results on different simulation data sets show that LGDLDA can accurately and effectively predict the disease-related lncRNAs. Furthermore, we applied the method to three real cancer data including gastric cancer, colorectal cancer and breast cancer to predict potential cancer-related lncRNAs.

The epistasis is prevalent in the SNP interactions. Some of the existing methods are focused on constructing models for two SNPs. Other methods only find the SNPs in consideration of one-objective function. In this paper, we present a unified fast framework integrating adaptive ant colony optimization algorithm with multiobjective functions for detecting SNP epistasis in GWAS datasets. We compared our method with other existing methods using synthetic datasets and applied the proposed method to Late-Onset Alzheimer’s Disease dataset. Our experimental results show that the proposed method outperforms other methods in epistasis detection, and the result of real dataset contributes to the research of mechanism underlying the disease.

Accumulating evidence suggests that circRNAs play crucial roles in human diseases. CircRNA-disease association prediction is extremely helpful in understanding pathogenesis, diagnosis, and prevention, as well as identifying relevant biomarkers. During the past few years, a large number of deep learning (DL) based methods have been proposed for predicting circRNA-disease association and achieved impressive prediction performance. However, there are two main drawbacks to these methods. The first is these methods underutilize biometric information in the data. Second, the features extracted by these methods are not outstanding to represent association characteristics between circRNAs and diseases. In this study, we developed a novel deep learning model, named iCircDA-NEAE, to predict circRNA-disease associations. In particular, we use disease semantic similarity, Gaussian interaction profile kernel, circRNA expression profile similarity, and Jaccard similarity simultaneously for the first time, and extract hidden features based on accelerated attribute network embedding (AANE) and dynamic convolutional autoencoder (DCAE). Experimental results on the circR2Disease dataset show that iCircDA-NEAE outperforms other competing methods significantly. Besides, 16 of the top 20 circRNA-disease pairs with the highest prediction scores were validated by relevant literature. Furthermore, we observe that iCircDA-NEAE can effectively predict new potential circRNA-disease associations.