The rapid development of spatial transcriptomics (ST) has revolutionized the study of spatial heterogeneity and increased the demand for comprehensive methods to effectively characterize spatial domains. As a prerequisite for ST data analysis, spatial domain characterization is a critical step for downstream analysis and biological interpretation. Here, we propose a deep graph contrastive learning framework (spG-CLF) for spatial transcriptomics, which leverages contrastive learning through graph convolutional networks to effectively learn features among spots, addressing the issue of poor cross-platform generalizability. By alternately performing attribute and topological denoising, our method specifically reduces noise in ST data. We demonstrate that s p GCLF is effective for spatial domain identification, trajectory inference, multi-slice integration, and type annotation.

Identifying cell types is a primary objective in single-cell RNA sequencing (scRNA-seq) analysis, and clustering is a widely used method for achieving this goal. However, the abundance of data and the presence of noise pose significant challenges for single-cell clustering. We propose a novel method called scGCNClustering, which leverages a deep graph convolution network (GCN) with attention. scGCNClustering comprises two core models. The first model is a deep GCN encoder that effectively preserves both the topological structure and feature information in scRNA-seq data, enabling accurate cell segregation. Additionally, we incorporate an attention module into the GCN encoder to capture precise global similarities between cells. The second model is a deep zero-inflated negative binomial (ZINB) decoder, which approximates the true distribution of scRNA-seq data. Extensive analysis conducted on six real scRNA-seq datasets demonstrates that scGCNClustering achieves promising performance in scRNA-seq clustering.

MicroRNAs (miRNAs) are closely related to a variety of human diseases, not only regulating gene expression, but also having an important role in human life activities and being viable targets of small molecule drugs for disease treatment. Current computational techniques to predict the potential associations between small molecule and miRNA are not that accurate. Here, we proposed a new computational method based on a deep autoencoder and a scalable tree boosting model (DAESTB), to predict associations between small molecule and miRNA. First, we constructed a high-dimensional feature matrix by integrating small molecule-small molecule similarity, miRNA-miRNA similarity and known small molecule-miRNA associations. Second, we reduced feature dimensionality on the integrated matrix using a deep autoencoder to obtain the potential feature representation of each small molecule-miRNA pair. Finally, a scalable tree boosting model is used to predict small molecule and miRNA potential associations. The experiments on two datasets demonstrated the superiority of DAESTB over various state-of-the-art methods. DAESTB achieved the best AUC value. Furthermore, in three case studies, a large number of predicted associations by DAESTB are confirmed with the public accessed literature. We envision that DAESTB could serve as a useful biological model for predicting potential small molecule-miRNA associations.

Circular RNAs (circRNAs) are a class of structurally stable endogenous noncoding RNA molecules. Increasing studies indicate that circRNAs play vital roles in human diseases. However, validating disease-related circRNAs in vivo is costly and time-consuming. A reliable and effective computational method to identify circRNA-disease associations deserves further studies. In this study, we propose a computational method called RNMFLP that combines robust nonnegative matrix factorization (RNMF) and label propagation algorithm (LP) to predict circRNA-disease associations. First, to reduce the impact of false negative data, the original circRNA-disease adjacency matrix is updated by matrix multiplication using the integrated circRNA similarity and the disease similarity information. Subsequently, the RNMF algorithm is used to obtain the restricted latent space to capture potential circRNA-disease pairs from the association matrix. Finally, the LP algorithm is utilized to predict more accurate circRNA-disease associations from the integrated circRNA similarity network and integrated disease similarity network, respectively. Fivefold cross-validation of four datasets shows that RNMFLP is superior to the state-of-the-art methods. In addition, case studies on lung cancer, hepatocellular carcinoma and colorectal cancer further demonstrate the reliability of our method to discover disease-related circRNAs.

Gene regulatory networks (GRNs) play a key role in biological processes. However, GRNs are diverse under different biological conditions. Reconstructing gene regulatory networks (GRNs) from gene expression has become an important opportunity and challenge in the past decades. Although there are a lot of existing methods to infer the topology of GRNs, such as mutual information, random forest, and partial least squares, the accuracy is still low due to the noise and high dimension of the expression data. In this paper, we introduce an ensemble Multivariate Adaptive Regression Splines (MARS) based method to reconstruct the directed GRNs from multifactorial gene expression data, called PBMarsNet. PBMarsNet incorporates part mutual information (PMI) to pre-weight the candidate regulatory genes and then uses MARS to detect the nonlinear regulatory links. Moreover, we apply bootstrap to run the MARS multiple times and average the outputs of each MARS as the final score of regulatory links. The results on DREAM4 challenge and DREAM5 challenge datasets show PBMarsNet has a superior performance and generalization over other state-of-the-art methods.

microRNAs (miRNAs) are small non-coding RNAs which modulate the stability of gene targets and their rates of translation into proteins at transcriptional level and post-transcriptional level. miRNA dysfunctions can lead to human diseases because of dysregulation of their targets. Correct miRNA target prediction will lead to better understanding of the mechanisms of human diseases and provide hints on curing them. In recent years, computational miRNA target prediction methods have been proposed according to the interaction rules between miRNAs and targets. However, these methods suffer from high false positive rates due to the complicated relationship between miRNAs and their targets. The rapidly growing number of experimentally validated miRNA targets enables predicting miRNA targets with high precision via accurate data analysis. Taking advantage of these known miRNA targets, a novel recommendation system model (miRTMC) for miRNA target prediction is established using a new matrix completion algorithm. In miRTMC, a heterogeneous network is constructed by integrating the miRNA similarity network, the gene similarity network, and the miRNA-gene interaction network. Our assumption is that the latent factors determining whether a gene is the target of miRNA or not are highly correlated, i.e., the adjacency matrix of the heterogeneous network is low-rank, which is then completed by using a nuclear norm regularized linear least squares model under non-negative constraints. Alternating direction method of multipliers (ADMM) is adopted to numerically solve the matrix completion problem. Our results show that miRTMC outperforms the competing methods in terms of various evaluation metrics. Our software package is available at https://github.com/hjiangcsu/miRTMC.

The advent of droplet-based transcriptomics platforms has enabled parallel screening over thousands or millions of cells. One of the challenging issues is to identify the rare cells from the ultra-large scRNA-seq data. Existing algorithms to find rare cells are time consuming or memory-exhausting. We propose an efficient and accurate method, Discovery of Rare Cells (DoRC). The rareness scores generated by DoRC can help biologists focus the downstream analyses only on a fraction of expression profiles within ultra-large scRNA-seq data. We also demonstrate the efficacy of DoRC in delineating human blood dendritic cell sub-types using ~68k single-cell expression profiles of human blood cells. DoRC can recover artificially planted rare cells and is sensitive to cell type identities as well.

MOTIVATION: Reconstructing gene regulatory networks (GRNs) based on gene expression profiles is still an enormous challenge in systems biology. Random forest-based methods have been proved a kind of efficient methods to evaluate the importance of gene regulations. Nevertheless, the accuracy of traditional methods can be further improved. With time-series gene expression data, exploiting inherent time information and high order time lag are promising strategies to improve the power and accuracy of GRNs inference. RESULTS: In this study, we propose a scalable, flexible approach called BiXGBoost to reconstruct GRNs. BiXGBoost is a bidirectional-based method by considering both candidate regulatory genes and target genes for a specific gene. Moreover, BiXGBoost utilizes time information efficiently and integrates XGBoost to evaluate the feature importance. Randomization and regularization are also applied in BiXGBoost to address the over-fitting problem. The results on DREAM4 and Escherichia coli datasets show the good performance of BiXGBoost on different scale of networks. AVAILABILITY AND IMPLEMENTATION: Our Python implementation of BiXGBoost is available at https://github.com/zrq0123/BiXGBoost. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.