Identifying spatial domains is critical for understanding breast cancer tissue heterogeneity and providing insights into tumor progression. However, dropout events introduces computational challenges and the lack of transparency in methods such as graph neural networks limits their interpretability. This study aimed to decipher disease progression-related spatial domains in breast cancer spatial transcriptomics by developing the three graph regularized non-negative matrix factorization (TGR-NMF). A unitization strategy was proposed to mitigate the impact of dropout events on the computational process, enabling utilization of the complete gene expression count data. By integrating one gene expression neighbor topology and two spatial position neighbor topologies, TGR-NMF was developed for constructing an interpretable low-dimensional representation of spatial transcriptomic data. The progressive lesion area that can reveal the progression of breast cancer was uncovered through heterogeneity analysis. Moreover, several related pathogenic genes and signal pathways on this area were identified by using gene enrichment and cell communication analysis.

Single-cell RNA sequencing (scRNA-seq) enables the resolution of cellular heterogeneity in diseases and facilitates the identification of novel cell types and subtypes. However, the grouping effects caused by cell-cell interactions are often overlooked in the development of tools for identifying subpopulations. We proposed LP_SGL which incorporates cell group structure to identify phenotype-associated subpopulations by integrating scRNA-seq, bulk expression and bulk phenotype data. Cell groups from scRNA-seq data were obtained by the Leiden algorithm, which facilitates the identification of subpopulations and improves model robustness. LP_SGL identified a higher percentage of cancer cells, T cells and tumor-associated cells than Scissor and scAB on lung adenocarcinoma diagnosis, melanoma drug response and liver cancer survival datasets, respectively. Biological analysis on three original datasets and four independent external validation sets demonstrated that the signaling genes of this cell subset can predict cancer, immunotherapy and survival.

Combination therapy has exhibited substantial potential compared to monotherapy. However, due to the explosive growth in the number of cancer drugs, the screening of synergistic drug combinations has become both expensive and time-consuming. Synergistic drug combinations refer to the concurrent use of two or more drugs to enhance treatment efficacy. Currently, numerous computational methods have been developed to predict the synergistic effects of anticancer drugs. However, there has been insufficient exploration of how to mine drug and cell line data at different granularity levels for predicting synergistic anticancer drug combinations. Therefore, this study proposes a granularity-level information fusion strategy based on the hypergraph transformer, named HypertranSynergy, to predict synergistic effects of anticancer drugs. HypertranSynergy introduces synergistic connections between cancer cell lines and drug combinations using hypergraph. Then, the Coarse-grained Information Extraction (CIE) module merges the hypergraph with a transformer for node embeddings. In the CIE module, Contranorm is a normalization layer that mitigates over-smoothing, while Gaussian noise addresses local information gaps. Additionally, the Fine-grained Information Extraction (FIE) module assesses fine-grained information's impact on predictions by employing similarity-aware matrices from drug/cell line features. Both CIE and FIE modules are integrated into HypertranSynergy. In addition, HypertranSynergy achieved the AUC of 0.93${\pm }$0.01 and the AUPR of 0.69${\pm }$0.02 in 5-fold cross-validation of classification task, and the RMSE of 13.77${\pm }$0.07 and the PCC of 0.81${\pm }$0.02 in 5-fold cross-validation of regression task. These results are better than most of the state-of-the-art models.

RNA-binding proteins (RBPs) can regulate biological functions by interacting with specific RNAs, and play an important role in many life activities. Therefore, the rapid identification of RNA-protein binding sites is crucial for functional annotation and site-directed mutagenesis. In this work, a new parallel network that integrates the multi-head attention mechanism and the expectation pooling is proposed, named MAHyNet. The left-branch network of MAHyNet hybrids convolutional neural networks (CNNs) and gated recurrent neural network (GRU) to extract the features of one-hot. The right-branch network is a two-layer CNN network to analyze physicochemical properties of RNA base. Specifically, the multi-head attention mechanism is a computational collection of multiple independent layers of attention, which can extract feature information from multiple dimensions. The expectation pooling combines probabilistic thinking with global pooling. This approach helps to reduce model parameters and enhance the model performance. The combination of CNN and GRU enables further extraction of high-level features in sequences. In addition, the study shows that appropriate hyperparameters have a positive impact on the model performance. Physicochemical properties can be used to supplement characterization information to improving model performance. The experimental results show that MAHyNet has better performance than other models.

Accurately identifying potential drug-target interactions (DTIs) is a critical step in accelerating drug discovery. Despite many studies that have been conducted over the past decades, detecting DTIs remains a highly challenging and complicated process. Therefore, we propose a novel method called SMGCN, which combines multiple similarity and multiple kernel fusion based on Graph Convolutional Network (GCN) to predict DTIs. In order to capture the features of the network structure and fully explore direct or indirect relationships between nodes, we propose the method of multiple similarity, which combines similarity fusion matrices with Random Walk with Restart (RWR) and cosine similarity. Then, we use GCN to extract multi-layer low-dimensional embedding features. Unlike traditional GCN methods, we incorporate Multiple Kernel Learning (MKL). Finally, we use the Dual Laplace Regularized Least Squares method to predict novel DTIs through combinatorial kernels in drug and target spaces. We conduct experiments on a golden standard dataset, and demonstrate the effectiveness of our proposed model in predicting DTIs through showing significant improvements in Area Under the Curve (AUC) and Area Under the Precision-Recall Curve (AUPR). In addition, our model can also discover some new DTIs, which can be verified by the KEGG BRITE Database and relevant literature.

Sparse regressions applied to cancer diagnosis suffer from noise reduction, gene grouping, and group significance evaluation. This paper presented the weighted group regularized logistic regression (WGRLR) for dealing with the above problems. Clean data was separated from noisy gene expression profile data, based on which gene grouping and model building were performed. An interpretable gene group significance evaluation criterion was proposed based on symmetrical uncertainty and module eigengene. A group-wise individual gene significance evaluation criterion was also presented. The performances of the proposed method were compared with WGGL, ASGL-CMI, SGL, GL, Elastic Net, and lasso on acute leukemia and brain cancer data. Experimental results demonstrate that the proposed method is superior to the other six methods in cancer diagnosis accuracy and gene selection.

BACKGROUND: Breast cancer is one of the most common cancers in women. It is necessary to classify breast cancer subtypes because different subtypes need specific treatment. Identifying biomarkers and classifying breast cancer subtypes is essential for developing appropriate treatment methods for patients. MiRNAs can be easily detected in tumor biopsy and play an inhibitory or promoting role in breast cancer, which are considered promising biomarkers for distinguishing subtypes. RESULTS: A new method combing ensemble regularized multinomial logistic regression and Cox regression was proposed for identifying miRNA biomarkers in breast cancer. After adopting stratified sampling and bootstrap sampling, the most suitable sample subset for miRNA feature screening was determined via ensemble 100 regularized multinomial logistic regression models. 124 miRNAs that participated in the classification of at least 3 subtypes and appeared at least 50 times in 100 integrations were screened as features. 22 miRNAs from the proposed feature set were further identified as the biomarkers for breast cancer by using Cox regression based on survival analysis. The accuracy of 5 methods on the proposed feature set was significantly higher than on the other two feature sets. The results of 7 biological analyses illustrated the rationality of the identified biomarkers. CONCLUSIONS: The screened features can better distinguish breast cancer subtypes. Notably, the genes and proteins related to the proposed 22 miRNAs were considered oncogenes or inhibitors of breast cancer. 9 of the 22 miRNAs have been proved to be markers of breast cancer. Therefore, our results can be considered in future related research.

This paper deals with the problems of cancer classification and grouped gene selection. The weighted gene co-expression network on cancer microarray data is employed to identify modules corresponding to biological pathways, based on which a strategy of dividing genes into groups is presented. Using the conditional mutual information within each divided group, an integrated criterion is proposed and the data-driven weights are constructed. They are shown with the ability to evaluate both the individual gene significance and the influence to improve correlation of all the other pairwise genes in each group. Furthermore, an adaptive sparse group lasso is proposed, by which an improved blockwise descent algorithm is developed. The results on four cancer data sets demonstrate that the proposed adaptive sparse group lasso can effectively perform classification and grouped gene selection.

This paper is concerned with the stabilization problem for a class of discrete-time networked control systems (NCSs) with bounded time delays and packet losses. The controlled plant is represented by a Takagi–Sugeno fuzzy model, and both the state feedback control and output feedback control cases are considered. By guaranteeing the decrement of Lyapunov functional at each control signal updating step, a less conservative stability condition for the state feedback NCSs is derived, and the corresponding stabilizing controller design method is also presented. Under an observer-based framework, the output feedback stabilization problem is further studied, where the main contribution is the development of the separation principle for NCSs. Illustrative examples are provided to show the advantage and effectiveness of the developed results.