Since genomics was proposed, the exploration of genes has been the focus of research. The emergence of single-cell RNA sequencing (scRNA-seq) technology makes it possible to explore gene expression at the single-cell level. Due to the limitations of sequencing technology, the data contains a lot of noise. At the same time, it also has the characteristics of high-dimensional and sparse. Clustering is a common method of analyzing scRNA-seq data. This paper proposes a novel single-cell clustering method called Robust Manifold Nonnegative Low-Rank Representation with Adaptive Total-Variation Regularization (MLRR-ATV). The Adaptive Total-Variation (ATV) regularization is introduced into Low-Rank Representation (LRR) model to reduce the influence of noise through gradient learning. Then, the linear and nonlinear manifold structures in the data are learned through Euclidean distance and cosine similarity, and more valuable information is retained. Because the model is non-convex, we use the Alternating Direction Method of Multipliers (ADMM) to optimize the model. We tested the performance of the MLRR-ATV model on eight real scRNA-seq datasets and selected nine state-of-the-art methods as comparison methods. The experimental results show that the performance of the MLRR-ATV model is better than the other nine methods.

Drug-drug interactions (DDIs) refer to the change in efficacy when two or more drugs taken at the same time. Reasonable DDI can enhance efficacy or reduce adverse drug reactions; otherwise, it may lead to adverse events. The recent DDI prediction methods, which use different graph neural networks to extract the drug substructures, convert the DDI prediction into the prediction of the relationship between the two drug substructures, and achieve good performance. However, these methods do not pay attention to the relationship between drug substructures extracted from the same drug. Therefore, we propose MSHGCL to constrain the relationship between drug substructures by multi-scale hierarchical graph contrastive learning module. Specifically, the intra-layer contrastive learning module constrains the relationship between drug substructures of the same scale, and the inter-layer contrastive learning module further constrains the relationship between drug substructures of adjacent layers. We evaluate MSHGCL on two real-world datasets. Experimental results show that the proposed MSHGCL method outperforms the most advanced DDI prediction method.

Predicting drug-disease associations is a crucial step in drug repositioning, especially with computational methods that quickly locate potential drug-disease pairs. Heterogenous network is a common tool for introducing multiple type relation information about drugs and diseases. However, the diversity of relations is ignored in most of existing methods, which makes them difficult to explore type semantic information with structure properties. Therefore, we propose a relation-centric GNN framework to encode critical association patterns. Firstly, we utilize a relation-centric graph, line graph, to represent the context of a drug-disease pair identified as the center node. The prediction problem is modeled to learn the embedding vector of the center node. Secondly, a multi-grained line graph neural network (MGLGNN) is designed to excavate fine-grained features that encapsulate local graph structures. We theoretically define a handful of typical nodes that can be regarded as high-order abstractions of relations in each type. Then, MGLGNN distills the local information and passes it to typical nodes from a global perspective. With learned multi-grained features, the center node automatically captures heterogenous relation semantics and structure patterns. Thirdly, a hierarchical contrastive learning (HCL) mechanism is proposed to ensure the quality of multi-grained features in an unsupervised way. Extensive experiments show the great potential of our model in mining drug-disease associations.

Biological studies have demonstrated that understanding the association between miRNAs and disease is critical for disease prevention, assessment, and therapy. However, traditional experimental methods for inferring these connections are not only costly but also inefficient. Hence, there is a pressing need to develop novel methods to improve the accuracy and efficiency of forecasting. Currently, graph convolutional networks (GCNs) techniques are one of the mainstream methods for predicting disease correlations. Nevertheless, traditional GCNs suffer from gradient vanishing and gradient explosion problems when dealing with long-range dependencies. To overcome these problems, we suggest a new approach called HGCMMDA, which relies on HyperGCN and combines a cosine annealing algorithm and a multi-head self-attention mechanism. In HGCMMDA, similarity networks for miRNAs and diseases are constructed, and GCN is used for feature extraction. A heterogeneity hypergraph is then built via HyperGCN for improved information propagation. Multi-head self-attention captures diverse node relations, while cosine annealing adjusts the learning rate. A combined BCE-Dice loss ensures accurate prediction. To evaluate the effectiveness of the proposed method, a comprehensive set of experiments was conducted using the Human microRNA Disease Database (HMDD v3.2). The method achieved a peak area under the receiver operating characteristic curve (AUC) of 0.9515, along with competitive performance in other evaluation metrics. The experimental findings indicate that HGCMMDA achieves notable enhancements over previously established approaches. These results strongly support the assertion that HGCMMDA serves as a dependable and effective framework for comprehensively exploring the intricate associations between microRNAs and human diseases.

Single-cell RNA sequencing (scRNA-seq) is a key technology for studying cellular heterogeneity. However, the high levels of sparsity and noise in scRNA-seq data present challenges for accurate cell clustering. To address this, we propose Graph-based ZINB Deep Clustering for Single-cell RNA-seq Data (scGZDC), a novel framework that operates within a variational autoencoder (VAE). The encoder of scGZDC employs a Graph Convolutional Network (GCN) to learn low-dimensional representations by leveraging both a preprocessed gene expression matrix and the cell-cell similarity graph. The decoder, in turn, employs a Graph Attention Network (GAT) to reconstruct gene expression counts via a Zero-Inflated Negative Binomial (ZINB) distribution, a distribution particularly well-suited for scRNA-seq data. To achieve end-to-end optimization, a Deep Embedding for Clustering (DEC) objective is integrated into the framework. Extensive experiments on public datasets demonstrate that scGZDC consistently outperforms existing methods. Our results show that unifying graph structural information with a suitable probabilistic model in an end-to-end clustering framework is an effective strategy for improving single-cell analysis.

Nowadays, technological advancements enable the simultaneous profiling of the epigenome, transcriptome, and proteome at the single-cell level, and an urgent need for tools to integrate such complex tri-modal data is demanded. In this paper, we propose a novel method named scHCHF, a scalable and unified Hierarchical Coarsening Hypergraph Framework. scHCHF first employs a hierarchical coarsening process to groups cells into hypervertices. A unified multiomics hypergraph is then constructed upon these hypervertices, which substantially reduces computational complexity and memory footprint. Subsequently, a hypergraph attention network captures high-order relationships and learns discriminative cell representations, guided by a weakly supervised prototypical contrastive loss. Building upon the pre-trained network, scHCHF further employs a fine-tuning paradigm to achieve accurate cell type annotation using a minimal number of labeled cells. Experiments on real tri-modal datasets demonstrate that scHCHF outperforms other state-of-the-art methods in both cell clustering and cell type annotation tasks.

Spatial transcriptomics provides a novel perspective for comprehending the intricate relationship between tissue structure and function, as well as for discovering new cell types and subtypes. However, it remains a significant challenge to accurately identify spatial domains with similar gene expression, which requires efficient combination of gene expression data , histology image information, and spatial location. To address this challenge, a novel dual denoising autoencoder with attention mechanism (STDDAE) is proposed. STDDAE integrates gene expression data, histology image information and spatial location, and the decoder consists of a master decoder and a follower decoder, which are jointly optimized to generate low-dimensional latent embeddings for precise spatial domain identification. The performance of STDDAE was evaluated across four datasets with varying resolutions and platforms. The experimental findings validated that STDDAE outperformed other cutting-edg methods in spatial domain identification, trajectory inference, and data denoising. Additionally, STDDAE successfully detected differentially expressed genes within identified spatial domains, which may be valuable in disease diagnosis, prognostic assessment, and treatment selection.

Numerous studies have demonstrated the regulatory role of circular RNA (circRNA) in various diseases, emphasizing the importance of identifying disease-related circRNAs. Although several computational models have been developed to predict circRNA-disease associations, the limited number of experimentally validated associations has resulted in the sparse association network. Therefore, there is a need for continuously improving circRNA-disease prediction models. In this study, we propose RPMVCDA, a computational model based on random perturbation and multi-view graph convolutional networks (GCNs), to predict circRNA-disease associations. Specifically, RPMVCDA first constructs multiple similarity networks of circRNAs and diseases, applying multi-view GCNs to obtain embedding representations. Second, to enable message passing between circRNA-disease samples, RPMVCDA constructs the feature similarity association network. Third, RPMVCDA introduces a random perturbation association network to further explore the potential associations, which is the highlight of the RPMVCDA. Finally, based on these three association networks, RPMVCDA utilizes the self-attention mechanism to generate high-quality features for circRNAs and diseases, which are used to calculate association scores. To evaluate the performance of RPMVCDA, five-fold cross-validation and case studies on the CircR2Disease dataset are performed, results of which shows that RPMVCDA outperforms the compared models, implying that it might be an alternative for predicting circRNA-disease associations.

The dysfunction of biological systems caused by disease-related genes is one of the inducements of complex diseases. To understand molecular mechanisms of complex diseases, the identification of disease-related gene modules in biological networks through community detection is emerging as a promising approach. However, most community detection methods are not suitable for biological networks because their topological structures are complex and the scale of biologically relevant modules are small. In this paper, a novel community detection method called MPSO-CD was proposed based on multi-objective particle swarm optimization, in which negative ratio association and ratio cut were employed as objective functions. Highlights of MPSO-CD are a mutation strategy based on clustering coefficient and the procedure of disease module screening referring to the internal connection density and functional similarity. Experimental results of social and synthetic complex networks indicate that MPSO-CD is comparable and often superior to four compared methods. Eventually, MPSO-CD is applied to the asthma gene co-expression network for identifying potential disease modules that provide the molecular mechanism information about asthma. Most of the captured modules have been proven to be associated with asthma through Gene Ontology and pathway enrichment analysis.

Drug repositioning (DR) has emerged as an effective method of identifying new indications for existing drugs. Many DR methods have demonstrated superior performance. However, most of them utilize a limited number of biological entities, ignoring the critical role of other entities in addressing data sparsity as well as improving model generalization capabilities. In addition, fully capturing high-order information of biological data still needs to be fully explored. To address above issues, a model based on transformer and enhanced multi-view contrastive learning (TEMCL) is proposed for predicting drug-disease associations (DDAs). Firstly, transformer is employed to obtain high-order features of nodes from similarity information. Secondly, based on similarity matrices and association matrices of nodes, two different types of views are constructed, i.e., homogeneous hypergraphs and heterogeneous association graphs. Among them, to alleviate sparsity problem existing in heterogeneous graphs, protein nodes as well as meta-path enhancement strategy are introduced. Thirdly, hypergraph convolutional network and heterogeneous graph transformer are used to extract node features on above two types of views, respectively. Contrastive learning is applied to obtain more representative features. Finally, multilayer perceptron (MLP) is used for predicting DDAs. Experiments show that TEMCL outperforms existing methods on DR task, exhibiting superior performance. In addition, case studies further demonstrate the effectiveness of this model. TEMCL provides new insights for identifying novel DDAs.

Cell type annotation refers to the process of categorizing and labeling cells to identify their specific cell types, which is crucial for understanding cell functions and biological processes. Although many methods have been developed for automated cell type annotation, they often encounter challenges such as batch effects due to variations in data distribution across platforms and species, thereby compromising their performance. To address batch effects, in this study, a pre-trained domain adaptation model based on structural similarity, named pscAdapt, is proposed for cell type annotation. Specifically, a pre-trained strategy is employed to initialize model parameters to learn the data distribution of source domain. This strategy is also combined with an adversarial learning strategy to train the domain adaptation network for achieving domain level alignment and reducing domain discrepancy. Furthermore, to better distinguish different types of cells, a structural similarity loss is designed, aiming to shorten distances between cells of the same type and increase distances between cells of different types in feature space, thus achieving cell level alignment and enhancing the discriminability of cell types. Comprehensive experiments were conducted on simulated datasets, cross-platforms datasets and cross-species datasets to validate the effectiveness of pscAdapt, results of which demonstrate that pscAdapt outperforms several popular cell type annotation methods.

Alzheimer's disease (AD) is a highly inheritable neurological disorder, and brain imaging genetics (BIG) has become a rapidly advancing field for comprehensive understanding its pathogenesis. However, most of the existing approaches underestimate the complexity of the interactions among factors that cause AD. To take full appreciate of these complexity interactions, we propose BIGFormer, a graph Transformer with local structural awareness, for AD diagnosis and identification of pathogenic mechanisms. Specifically, the factors interaction graph is constructed with lesion brain regions and risk genes as nodes, where the connection between nodes intuitively represents the interaction between nodes. After that, a perception with local structure awareness is built to extract local structure around nodes, which is then injected into node representation. Then, the global reliance inference component assembles the local structure into higher-order structure, and multi-level interaction structures are jointly aggregated into a classification projection head for disease state prediction. Experimental results show that BIGFormer demonstrated superiority in four classification tasks on the AD neuroimaging initiative dataset and proved to identify biomarkers closely intimately related to AD.

Community detection has attracted growing interest, with multi-objective evolutionary algorithms proving to be highly competitive in this area. In this paper, a community detection method based on a multi-objective neighborhood coevolution genetic algorithm, NCMOGA, is proposed. To improve the computational efficiency in large-scale networks, NCMOGA introduces a network processing strategy to simplify the network before and during evolution. A neighborhood coevolution strategy is proposed, in which the corresponding subpopulation is formed according to the neighborhood of each individual. A series of operations such as crossover, mutation and update are performed in the subpopulation, emphasizing the synergy between individuals and their neighbors. Mating selection and crossover operations are performed based on the center selection idea of density peak clustering, and the most important nodes are selected to generate offspring. The effectiveness of NCMOGA is verified on synthetic networks and real-world networks. In addition, the results in guiding the classification of disease and healthy samples demonstrate the high quality of the modules detected by NCMOGA.

Recent developments in spatial transcriptomics technologies have made it possible to obtain gene expression profiles while maintaining spatial context. Precisely identifying spatial domains is essential for downstream analysis, requiring the effective integration of gene expression profiles with spatial information. To overcome the challenge of low accuracy in spatial domain identification, this paper proposed a deep learning model called LGAGCN based on local and global information. It used graph convolutional network to learn the features of local and global views and employed an attention mechanism to integrate embeddings from different views. Moreover, experiments were conducted on the human dorsolateral prefrontal cortex (DLPFC) dataset and the human breast cancer (HBC) dataset to evaluate the effectiveness of the model. The experimental results showed that LGAGCN outperformed state-of-the-art methods in spatial clustering task.

In diagnosing Alzheimer’s Disease (AD), structural Magnetic Resonance Imaging (sMRI) is crucial, providing axial, coronal, and sagittal views for a comprehensive analysis of brain structures and pathological changes. Region of Interest (ROI) techniques in neuroimaging further allow detailed examination of structural and functional changes linked to AD. Additionally, certain SNPs have been identified as significant genetic markers for AD risk. Given the capabilities of Convolutional Neural Networks (CNNs) and Transformer models in handling multimodal data, this study introduces a novel hybrid network, DAResNet-ViT, for AD diagnosis. The model utilizes 24 key sMRI slices from each view per participant, combined with ROI features and genetic data, for classifying subjects. Data from two Alzheimer’s Disease Neuroimaging Initiative (ADNI) datasets were preprocessed and used to train and validate DAResNet-ViT. The model was evaluated through experiments focusing on AD diagnosis and the prediction of Mild Cognitive Impairment (MCI) conversion, with its effectiveness demonstrated in ablation studies and comparative experiments.

Exploring new therapeutic applications for existing drugs can effectively reduce drug development costs. However, current drug-disease association (DDA) prediction methods often fail to effectively integrate multi-domain information. The lack of multi-domain information integration causes these methods to heavily rely on prior knowledge, thereby limiting their generalization ability. To address this issue, we developed a Multi-Domain Graph Collaborative Contrastive Learning (MNGCCL) model for DDA prediction. In the MNGCCL framework, a feature extraction module is designed to effectively extract both single-domain and multi-domain features. The single-domain and multi-domain feature extraction components in this module run in parallel, extracting key features of drugs and diseases from different latent spaces (e.g., homogeneous and heterogeneous networks). MNGCCL employs graph collaborative contrastive learning to integrate these features and enhances information interaction by designing new node scoring for negative sample sampling. This significantly enriches the semantic features of drugs and diseases. In DDA prediction, MNGCCL outperforms other state-of-the-art models across various datasets and partitioning methods. Notably, MNGCCL excels in drug repositioning for Parkinson’s disease and Alzheimer’s disease, as well as handling data sparsity. These findings highlight its tremendous potential for drug repositioning and DDA prediction, especially in the context of sparse omics data.

The majority of studies on seizure prediction have concentrated on temporal and frequency features, which may result in inconsistencies when evaluating the accuracy of pre-dictions. To address this issue, we propose an innovative seizure prediction model that incorporates channel features as one of the key component. The model effectively integrates time, frequency and channel features by combining three convolutional neural networks (CNNs) and three transformer encoders. We validated our method on the CHB-MIT dataset, obtaining 99.00% accuracy, 99.10% sensitivity and 0.011/h false prediction rate (FPR). The experimental results demonstrate the efficient performance of our method in EEG signal classification and prediction, or comparable to state-of-the-art models.

Magnetic resonance imaging (MRI) technology shows significant potential in predicting early pathological changes associated with Alzheimer's disease (AD). However, the complexity of MRI and their multidimensional characteristics pose challenges in model classification tasks, and single-scale features often fail to capture subtle changes in lesion areas effectively. To improve the accuracy of AD predictions, we propose a network model based on multi-scale features and a dual self-attention mechanism (MSDA). This model integrates depthwise separable convolutions with an improved self-attention mechanism, thereby enhancing the classification ability for AD. First, MRI undergo head motion correction, image alignment, and skull stripping to enhance the model's capability to extract features related to AD lesions. Second, we designed a multi-scale convolutional network structure that utilizes depthwise separable convolution kernels of varying sizes, allowing the network to effectively capture multi-scale feature information from MRI and accurately identify lesion areas. Finally, we introduced a dual self-attention module, which includes channel self-attention and spatial self-attention, further augmenting the model's ability to extract lesion features by learning the differences in features across different categories of MRI in both channel and spatial dimensions. Experimental results indicate that the MSDA network model demonstrates exceptional performance in classifying normal controls (NC) and AD within the ADNI dataset, outperforming existing models in classification accuracy, performance, and generalization capability. The accuracy, sensitivity, and specificity of the model reached 97.8%, 96.3%, and 99.4%, respectively.

The advent and development of single-cell RNA sequencing (scRNA-seq) have provided new avenues for exploring cellular heterogeneity. Although many researchers have designed and developed efficient models to address cell heterogeneity and diversity by clustering cells into several groups, the performance of these methods may need improvement due to the characteristics of scRNA-seq data, such as high dimensionality, sparsity, and high dropout rates. In this paper, we propose a new method that couples low-rank representation (LRR) and concept factorization (CF) to learn a better clustering assignment matrix from both global and local perspectives, named SLRRGCF. Specifically, the LRR with similarity constraints based on tired random walk (TRW) can reduce the dimensionality of high-dimensional data while capturing more comprehensive global structure. At the same time, hypergraph regularization and CF are utilized to capture the local structure of the data further and directly obtain the clustering assignment matrix. We evaluated the performance of SLRRGCF on several real datasets, and comparisons with other competitive methods validated the effectiveness of our approach.

Single nucleotide polymorphism (SNPs) data have become abundant thanks to the quick advancement of high-throughput sequencing technology, which provides convenience for genome-wide association studies. Single SNPs have been proven to be the cause of some diseases, and the emergence of complex diseases is often thought to be the result of the interaction of multiple SNPs. However, the possible interaction of millions of SNPs imposes a heavy computational burden for uncovering complex disease mechanisms. The existing SNP-SNP interaction detection algorithms frequently have flaws including high computation complexity and poor optimization effectiveness. In this study, a particle swarm optimization algorithm based on multi-population mutual learning (PSOMPML) is proposed to detect SNP-SNP interactions. In this algorithm, the mutual learning strategy is introduced to deal with different particles in different sub-populations to facilitate knowledge exchange. In addition, the elite preservation mechanism is incorporated into PSOMPML, to better preserve the good SNPs in the elite particles. The promising region local search strategy searches the optimal solution along the target solution and its near space to increase the convergence speed of the proposed algorithm. Experiments on simulated data sets and real data also demonstrate the effectiveness of the proposed algorithm.

Alzheimer's disease (AD) is a neurodegenerative disorder that progresses in a slow and irreversible manner. Although many computer-aided methods have been used to diagnose AD, the issue of underutilization of detailed information and features persists. In this study, we propose a new AD diagnostic network (FPRes-Net) that can fully learn the rich information of 3D MRI slices by extracting multi-scale features and feature fusion. Firstly, in order to fully extract multi-scale information, a network structure combining ResNet-50 with feature pyramids was designed. Next, a feature fusion method was designed to reduce noise and increase the importance of important features. Finally, a visually interpretable method called Gradient-weighted Class Activation Mapping (Grad-CAM) was introduced to visualize important feature regions in AD diagnosis. Experimental analysis was conducted on the publicly accessible ADNI-1 dataset, and our proposed FPRes-Net model performed better than other advanced research methods, with an accuracy rate of 99.5%. Our proposed model can be effectively used for clinical diagnosis of AD.

Although the density peak clustering (DPC) algorithm can effectively distribute samples and quickly identify noise points, it lacks adaptability and cannot consider the local data structure. In addition, clustering algorithms generally suffer from high time complexity. Prior research suggests that clustering algorithms grounded in P systems can mitigate time complexity concerns. Within the realm of membrane systems (P systems), spiking neural P systems (SN P systems), inspired by biological nervous systems, are third-generation neural networks that possess intricate structures and offer substantial parallelism advantages. Thus, this study first improved the DPC by introducing the maximum nearest neighbor distance and K-nearest neighbors (KNN). Moreover, a method based on delayed spiking neural P systems (DSN P systems) was proposed to improve the performance of the algorithm. Subsequently, the DSNP-ANDPC algorithm was proposed. The effectiveness of DSNP-ANDPC was evaluated through comprehensive evaluations across four synthetic datasets and 10 real-world datasets. The proposed method outperformed the other comparison methods in most cases.

Neonatal epilepsy is a common emergency phenomenon in neonatal intensive care units (NICUs), which requires timely attention, early identification, and treatment. Traditional detection methods mostly use supervised learning with enormous labeled data. Hence, this study offers a semi-supervised hybrid architecture for detecting seizures, which combines the extracted electroencephalogram (EEG) feature dataset and convolutional autoencoder, called Fd-CAE. First, various features in the time domain and entropy domain are extracted to characterize the EEG signal, which helps distinguish epileptic seizures subsequently. Then, the unlabeled EEG features are fed into the convolutional autoencoder (CAE) for training, which effectively represents EEG features by optimizing the loss between the input and output features. This unsupervised feature learning process can better combine and optimize EEG features from unlabeled data. After that, the pre-trained encoder part of the model is used for further feature learning of labeled data to obtain its low-dimensional feature representation and achieve classification. This model is performed on the neonatal EEG dataset collected at the University of Helsinki Hospital, which has a high discriminative ability to detect seizures, with an accuracy of 92.34%, precision of 93.61%, recall rate of 98.74%, and F1-score of 95.77%, respectively. The results show that unsupervised learning by CAE is beneficial to the characterization of EEG signals, and the proposed Fd-CAE method significantly improves classification performance.

Recent advancements in spatially transcriptomics (ST) technologies have enabled the comprehensive measurement of gene expression profiles while preserving the spatial information of cells. Combining gene expression profiles and spatial information has been the most commonly used method to identify spatial functional domains and genes. However, most existing spatial domain decipherer methods are more focused on spatially neighboring structures and fail to take into account balancing the self-characteristics and the spatial structure dependency of spots. Therefore, we propose a novel model called SpaGCAC, which recognizes spatial domains with the help of an adaptive feature-spatial balanced graph convolutional network named AFSBGCN. The AFSBGCN can dynamically learn the relationship between spatial local topology structures and the self-characteristics of spots by adaptively increasing or declining the weight on the self-characteristics during message aggregation. Moreover, to better capture the local structures of spots, SpaGCAC exploits a local topology structure contrastive learning strategy. Meanwhile, SpaGCAC utilizes a probability distribution contrastive learning strategy to increase the similarity of probability distributions for points belonging to the same category. We validate the performance of SpaGCAC for spatial domain identification on four spatial transcriptomic datasets. In comparison with seven spatial domain recognition methods, SpaGCAC achieved the highest NMI median of 0.683 and the second highest ARI median of 0.559 on the multi-slice DLPFC dataset. SpaGCAC achieved the best results on all three other single-slice datasets. The above-mentioned results show that SpaGCAC outperforms most existing methods, providing enhanced insights into tissue heterogeneity.

The advent of single-cell RNA sequencing (scRNA-seq) technology offers the opportunity to conduct biological research at the cellular level. Single-cell type identification based on unsupervised clustering is one of the fundamental tasks of scRNA-seq data analysis. Although many single-cell clustering methods have been developed recently, few can fully exploit the deep potential relationships between cells, resulting in suboptimal clustering. In this paper, we propose scGAMF, a graph autoencoder-based multi-level kernel subspace fusion framework for scRNA-seq data analysis. Based on multiple top feature sets, scGAMF unifies deep feature embedding and kernel space analysis into a single framework to learn an accurate clustering affinity matrix. First, we construct multiple top feature sets to avoid the high variability caused by single feature set learning. Second, scGAMF uses a graph autoencoder (GAEs) to extract deep information embedded in the data, and learn embeddings including gene expression patterns and cell-cell relationships. Third, to fully explore the deep potential relationships between cells, we design a multi-level kernel space fusion strategy. This strategy uses a kernel expression model with adaptive similarity preservation to learn a self-expression matrix shared by all embedding spaces of a given feature set, and a consensus affinity matrix across multiple top feature sets. Finally, the consensus affinity matrix is used for spectral clustering, visualization, and identification of gene markers. Extensive validation on real datasets shows that scGAMF achieves higher clustering accuracy than many popular single-cell analysis methods.

Advances in high-throughput single-cell RNA sequencing (scRNA-seq) technology have provided more comprehensive biological information on cell expression. Clustering analysis is a critical step in scRNA-seq research and provides clear knowledge of the cell identity. Unfortunately, the characteristics of scRNA-seq data and the limitations of existing technologies make clustering encounter a considerable challenge. Meanwhile, some existing methods treat different features equally and ignore differences in feature contributions, which leads to a loss of information. To overcome limitations, we introduce a weighted distance constraint into the construction of the similarity graph and combine the similarity constraint. We propose the Joint Automatic Weighting Similarity Graph and Low-rank Representation (JAGLRR) clustering method. Evaluating the contributions of each feature and assigning various weight values can increase the significance of valuable features while decreasing the interference of redundant features. The similarity constraint allows the model to generate a more symmetric affinity matrix. Benefitting from that affinity matrix, JAGLRR recovers the original linear relationship of the data more accurately and obtains more discriminative information. The results on simulated datasets and 8 real datasets show that JAGLRR outperforms 11 existing comparison methods in clustering experiments, with higher clustering accuracy and stability.

Machine learning techniques have become increasingly important in analyzing single-cell RNA and identifying cell types, providing valuable insights into cellular development and disease mechanisms. However, the presence of batch effects poses major challenges in scRNA-seq analysis due to data distribution variation across batches. Although several batch effect mitigation algorithms have been proposed, most of them focus only on the correlation of local structure embeddings, ignoring global distribution matching and discriminative feature representation in batch correction. In this paper, we proposed the discriminative domain adaption network (D2AN) for joint batch effects correction and type annotation with single-cell RNA-seq. Specifically, we first captured the global low-dimensional embeddings of samples from the source and target domains by adversarial domain adaption strategy. Second, a contrastive loss is developed to preliminarily align the source domain samples. Moreover, the semantic alignment of class centroids in the source and target domains is achieved for further local alignment. Finally, a self-paced learning mechanism based on inter-domain loss is adopted to gradually select samples with high similarity to the target domain for training, which is used to improve the robustness of the model. Experimental results demonstrated that the proposed method on multiple real datasets outperforms several state-of-the-art methods.

The roles of brain region activities and genotypic functions in the pathogenesis of Alzheimer's disease (AD) remain unclear. Meanwhile, current imaging genetics methods are difficult to identify potential pathogenetic markers by correlation analysis between brain network and genetic variation. To discover disease-related brain connectome from the specific brain structure and the fine-grained level, based on the Automated Anatomical Labeling (AAL) and human Brainnetome atlases, the functional brain network is first constructed for each subject. Specifically, the upper triangle elements of the functional connectivity matrix are extracted as connectivity features. The clustering coefficient and the average weighted node degree are developed to assess the significance of every brain area. Since the constructed brain network and genetic data are characterized by non-linearity, high-dimensionality, and few subjects, the deep subspace clustering algorithm is proposed to reconstruct the original data. Our multilayer neural network helps capture the non-linear manifolds, and subspace clustering learns pairwise affinities between samples. Moreover, most approaches in neuroimaging genetics are unsupervised learning, neglecting the diagnostic information related to diseases. We presented a label constraint with diagnostic status to instruct the imaging genetics correlation analysis. To this end, a diagnosis-guided deep subspace clustering association (DDSCA) method is developed to discover brain connectome and risk genetic factors by integrating genotypes with functional network phenotypes. Extensive experiments prove that DDSCA achieves superior performance to most association methods and effectively selects disease-relevant genetic markers and brain connectome at the coarse-grained and fine-grained levels.

Accumulating evidence indicates that microRNAs (miRNAs) can control and coordinate various biological processes. Consequently, abnormal expressions of miRNAs have been linked to various complex diseases. Recognizable proof of miRNA-disease associations (MDAs) will contribute to the diagnosis and treatment of human diseases. Nevertheless, traditional experimental verification of MDAs is laborious and limited to small-scale. Therefore, it is necessary to develop reliable and effective computational methods to predict novel MDAs. In this work, a multi-kernel graph attention deep autoencoder (MGADAE) method is proposed to predict potential MDAs. In detail, MGADAE first employs the multiple kernel learning (MKL) algorithm to construct an integrated miRNA similarity and disease similarity, providing more biological information for further feature learning. Second, MGADAE combines the known MDAs, disease similarity, and miRNA similarity into a heterogeneous network, then learns the representations of miRNAs and diseases through graph convolution operation. After that, an attention mechanism is introduced into MGADAE to integrate the representations from multiple graph convolutional network (GCN) layers. Lastly, the integrated representations of miRNAs and diseases are input into the bilinear decoder to obtain the final predicted association scores. Corresponding experiments prove that the proposed method outperforms existing advanced approaches in MDA prediction. Furthermore, case studies related to two human cancers provide further confirmation of the reliability of MGADAE in practice.

CircRNA has been proved to play an important role in the diseases diagnosis and treatment. Considering that the wet-lab is time-consuming and expensive, computational methods are viable alternative in these years. However, the number of circRNA-disease associations (CDAs) that can be verified is relatively few, and some methods do not take full advantage of dependencies between attributes. To solve these problems, this paper proposes a novel method based on Kernel Fusion and Deep Auto-encoder (KFDAE) to predict the potential associations between circRNAs and diseases. Firstly, KFDAE uses a non-linear method to fuse the circRNA similarity kernels and disease similarity kernels. Then the vectors are connected to make the positive and negative sample sets, and these data are send to deep auto-encoder to reduce dimension and extract features. Finally, three-layer deep feedforward neural network is used to learn features and gain the prediction score. The experimental results show that compared with existing methods, KFDAE achieves the best performance. In addition, the results of case studies prove the effectiveness and practical significance of KFDAE, which means KFDAE is able to capture more comprehensive information and generate credible candidate for subsequent wet-lab.

Circular RNAs (circRNAs) have emerged as a novel class of non-coding RNAs with regulatory roles in disease pathogenesis. Computational models aimed at predicting circRNA-disease associations offer valuable insights into disease mechanisms, thereby enabling the development of innovative diagnostic and therapeutic approaches while reducing the reliance on costly wet experiments. In this study, SGFCCDA is proposed for predicting potential circRNA-disease associations based on scale graph convolutional networks and feature convolution. Specifically, SGFCCDA integrates multiple measures of circRNA and disease similarity and combines known association information to construct a heterogeneous network. This network is then explored by scale graph convolutional networks to capture both topological and attribute information. Additionally, convolutional neural networks are employed to further learn the features and obtain higher-order feature representations containing richer information about nodes. The Hadamard product is utilized to effectively combine circRNA features with disease features, and a multilayer perceptron is applied to predict the association between each pair of circRNA and disease. Five-fold cross validation experiments conducted on the CircR2Disease dataset demonstrate the accurate prediction capabilities of SGFCCDA in identifying potential circRNA-disease associations. Furthermore, case studies provide further confirmation of SGFCCDA's ability to identify disease-associated circRNAs.

Numerous scientific studies have found a link between diverse microorganisms in the human body and complex human diseases. Because traditional experimental approaches are time-consuming and expensive, using computational methods to identify microbes correlated with diseases is critical. In this paper, a new microbe-disease association prediction model is proposed that combines a multi-view multi-modal network and a multi-scale feature fusion mechanism, called M3HOGAT. Firstly, a microbe-disease association network and multiple similarity views are constructed based on multi-source information. Then, consider that neighbor information from disparate orders might be more adept at learning node representations. Consequently, the higher-order graph attention network (HOGAT) is devised to aggregate neighbor information from disparate orders to extract microbe and disease features from different networks and views. Given that the embedding features of microbe and disease from different views possess varying importance, a multi-scale feature fusion mechanism is employed to learn their interaction information, thereby generating the final feature of microbes and diseases. Finally, an inner product decoder is used to reconstruct the microbe-disease association matrix. Compared with five state-of-the-art methods on the HMDAD and Disbiome datasets, the results of 5-fold cross-validations show that M3HOGAT achieves the best performance. Furthermore, case studies on asthma and obesity confirm the effectiveness of M3HOGAT in identifying potential disease-related microbes.

The pathogenesis of Alzheimer's disease (AD) is extremely intricate, which makes AD patients almost incurable. Recent studies have demonstrated that analyzing multi-modal data can offer a comprehensive perspective on the different stages of AD progression, which is beneficial for early diagnosis of AD. In this paper, we propose a deep self-reconstruction fusion similarity hashing (DS-FSH) method to effectively capture the AD-related biomarkers from the multi-modal data and leverage them to diagnose AD. Given that most existing methods ignore the topological structure of the data, a deep self-reconstruction model based on random walk graph regularization is designed to reconstruct the multi-modal data, thereby learning the nonlinear relationship between samples. Additionally, a fused similarity hash based on anchor graph is proposed to generate discriminative binary hash codes for multi-modal reconstructed data. This allows sample fused similarity to be effectively modeled by a fusion similarity matrix based on anchor graph while modal correlation can be approximated by Hamming distance. Especially, extracted features from the multi-modal data are classified using deep sparse autoencoders classifier. Finally, experiments conduct on the AD Neuroimaging Initiative database show that DS-FSH outperforms comparable methods of AD classification. To conclude, DS-FSH identifies multi-modal features closely associated with AD, which are expected to contribute significantly to understanding of the pathogenesis of AD.

Feature selection is a critical component of data mining and has garnered significant attention in recent years. However, feature selection methods based on information entropy often introduce complex mutual information forms to measure features, leading to increased redundancy and potential errors. To address this issue, we propose FSCME, a feature selection method combining Copula correlation (Ccor) and the maximum information coefficient (MIC) by entropy weights. The FSCME takes into consideration the relevance between features and labels, as well as the redundancy among candidate features and selected features. Therefore, the FSCME utilizes Ccor to measure the redundancy between features, while also estimating the relevance between features and labels. Meanwhile, the FSCME employs MIC to enhance the credibility of the correlation between features and labels. Moreover, this study employs the Entropy Weight Method (EWM) to evaluate and assign weights to the Ccor and MIC. The experimental results demonstrate that FSCME yields a more effective feature subset for subsequent clustering processes, significantly improving the classification performance compared to the other six feature selection methods.

Increasing microRNAs (miRNAs) have been confirmed to be inextricably linked to various diseases, and the discovery of their associations has become a routine way of treating diseases. To overcome the time-consuming and laborious shortcoming of traditional experiments in verifying the associations of miRNAs and diseases (MDAs), a variety of computational methods have emerged. However, these methods still have many shortcomings in terms of predictive performance and accuracy. In this study, a model based on multiple graph convolutional networks and random forest (MGCNRF) was proposed for the prediction MDAs. Specifically, MGCNRF first mapped miRNA functional similarity and sequence similarity, disease semantic similarity and target similarity, and the known MDAs into four different two-layer heterogeneous networks. Second, MGCNRF applied four heterogeneous networks into four different layered attention graph convolutional networks (GCNs), respectively, to extract MDA embeddings. Finally, MGCNRF integrated the embeddings of every MDA into the features of the miRNA-disease pair and predicted potential MDAs through the random forest (RF). Fivefold cross-validation was applied to verify the prediction performance of MGCNRF, which outperforms the other seven state-of-the-art methods by area under curve. Furthermore, the accuracy and the case studies of different diseases further demonstrate the scientific rationale of MGCNRF. In conclusion, MGCNRF can serve as a scientific tool for predicting potential MDAs.

Single-cell RNA sequencing (scRNA-seq) technology is famous for providing a microscopic view to help capture cellular heterogeneity. This characteristic has advanced the field of genomics by enabling the delicate differentiation of cell types. However, the properties of single-cell datasets, such as high dropout events, noise, and high dimensionality, are still a research challenge in the single-cell field. To utilize single-cell data more efficiently and to better explore the heterogeneity among cells, a new graph autoencoder (GAE)-based consensus-guided model (scGAC) is proposed in this article. The data are preprocessed into multiple top-level feature datasets. Then, feature learning is performed by using GAEs to generate new feature matrices, followed by similarity learning based on distance fusion methods. The learned similarity matrices are fed back to the GAEs to guide their feature learning process. Finally, the abovementioned steps are iterated continuously to integrate the final consistent similarity matrix and perform other related downstream analyses. The scGAC model can accurately identify critical features and effectively preserve the internal structure of the data. This can further improve the accuracy of cell type identification.

CircRNA as a biomarker has been shown to have an essential effect on the occurrence and prognosis of a wide range of human diseases. Because of the high cost of wet experiments, computational methods are widely used to explore circRNA. However, the performance and robustness of the computational models still need to be further improved. To solve these problems, this paper proposes a novel method based on graph random propagation network and multi-head dynamic graph attention network (GRPGAT) to predict the potential associations between circRNAs and diseases. Firstly, GRPGAT uses centered kernel alignment method to fuse the circRNA similarity kernels and disease similarity kernels. Then the integrated vectors build a heterogeneous graph and are sent to a graph random propagation network. The remaining nodes are fed into a multi-head dynamic attention network for feature extraction. Finally, a four-layer Multilayer Perceptron is used to learn features and gain the prediction scores. Experiments are supported by cirR2Disease, and achieve Area Under Curve (AUC) scores of 0.9636 in 5-fold cross validation. In comparison with the state-of-the-art models, GRPGAT also shows superior performance.

Identification of disease-associated long non-coding RNAs (lncRNAs) facilitates the understanding of the pathogenesis of complex diseases. Many different types of computational models have been proposed. Although some of them have achieved encouraging results in predicting disease-associated lncRNAs, how to obtain stable results is still a challenge. In this paper, we propose a computational model based on an ensemble learning framework via the adaptive random forests, in short, idenLD-AREL. The idenLD-AREL integrates multiple random forest predictors and adaptive strategies to predict the scores of potential lncRNA-disease associations (LDAs), which ensure the stability and accuracy of the prediction results. In addition, there are a large number of false negative samples in the association datasets. For this reason, the resampling strategy is applied to idenLD-AREL to balance the samples. The idenLD-AREL is assessed by five-fold cross-validation in both the benchmark dataset and independent test set, showing excellent performance. Besides, the experimental results of the case study further demonstrate the effectiveness of the idenLD-AREL in predicting potential LDAs. The demo codes of the iLncDA-RSN are available online at https://github.com/CDMBlab/idenLD-AREL.

As science and technology continue to advance, more and more studies show that there are so many miRNA-disease associations (MDAs). Known MDAs will help us prevent and treat certain diseases. However, traditional wet experiments greatly consume manpower and time. Therefore, it is critical that a few reliable methods for predicting MDAs are developed. In this study, we have come up with a machine-learning method for quadratic prediction MDAs (MLQP). MLQP is an improvement method on the traditional least squares method. In this method, MDAs information can be used more by using Weight K Nearest Known Neighbors (WKNKN) method and neighborhood similarity processing (NSP). Gaussian interaction profile (GIP) kernel similarity is applied to improve the accuracy of prediction results. The regularization least squares method is also utilized to generate the prediction scores. AUC value of MLQP under five-fold cross-validation is 0.957. MLQP outperforms other methods in predicting MDAs, as demonstrated by the final experimental results. Finally, the efficacy and practicality of the MLQP will be further verified in the study of four specific diseases.

Microbes play a crucial role within the human body and are closely associated with the occurrence and development of numerous diseases. Studies have shown that disruptions in the composition and functionality of microbes can lead to immune system imbalances, inflammatory responses, and subsequently impact human health. Therefore, developing computational models to discover the potential connections between microbes and diseases is currently a hot topic. In this paper, a computational framework based on the multiple kernel fusion of graph embedding with sampling and aggregation (GraphSAGE) and dual Laplace regularized least squares called MKGSAGE is proposed for predicting potential links between microbe and disease. First, multiple layers embedding features of microbe and disease are learned from the initial input features by GraphSAGE. The kernel matrices are then calculated separately for each layer based on the Gaussian interaction profile (GIP). Furthermore, the multiple kernel fusion method is proposed for fusing kernel matrices of each layer and the initial similarity matrix. Dual Laplacian regularized least squares are finally applied for potential microbe-disease association prediction. Compared with six state-of-the-art methods on the HMDAD dataset, 5-fold cross-validations show that MKGSAGE performs best. In addition, case studies on asthma and inflammatory bowel disease further validate the effectiveness of MKGSAGE on discovering novel microbe-disease associations.

Single-cell RNA sequencing (scRNA-seq) data are collected at an unheard-of rate thanks to the advancement of high-throughput sequencing technologies. However, due to the limitations of current technology, scRNA-seq is sometimes unable to capture the expressed genes, resulting in a large number of zero counts (also known as dropout events) in the data. These dropout events can cause data loss in the gene expression matrix and severely hampers the accuracy of downstream analysis. To address this problem, in this paper, we propose a new imputation method called scNMF-impute. The scNMF-impute method imputes the dropout events and performs dimensionality reduction under the framework of nonnegative matrix factorization (NMF). To effectively identify the location of the dropout and recover the value of the dropout, we explicitly model the dropout events as a matrix. Therefore, the gene expression matrix without dropout is represented as the sum of the original data matrix and the dropout matrix. In addition, to reduce the influence of dropout on factorization, we introduce the similarity information between genes into the NMF model. The introduction of gene similarity information can ensure the accurate recovery of data structures obscured by dropout events in the gene expression matrix. We conducted extensive experiments on simulated datasets and real scRNA-seq datasets to verify the effectiveness of scNMF-impute and other state-of-the-art methods. The results show that scNMF-impute can accurately calculate missing data and restore true gene expression, thus improving the accuracy of existing clustering methods and obtaining more accurate cell clustering results.

BACKGROUND: Constructing molecular interaction networks from microarray data and then identifying disease module biomarkers can provide insight into the underlying pathogenic mechanisms of non-small cell lung cancer. A promising approach for identifying disease modules in the network is community detection. RESULTS: In order to identify disease modules from gene co-expression networks, a community detection method is proposed based on multi-objective optimization genetic algorithm with decomposition. The method is named DM-MOGA and possesses two highlights. First, the boundary correction strategy is designed for the modules obtained in the process of local module detection and pre-simplification. Second, during the evolution, we introduce Davies-Bouldin index and clustering coefficient as fitness functions which are improved and migrated to weighted networks. In order to identify modules that are more relevant to diseases, the above strategies are designed to consider the network topology of genes and the strength of connections with other genes at the same time. Experimental results of different gene expression datasets of non-small cell lung cancer demonstrate that the core modules obtained by DM-MOGA are more effective than those obtained by several other advanced module identification methods. CONCLUSIONS: The proposed method identifies disease-relevant modules by optimizing two novel fitness functions to simultaneously consider the local topology of each gene and its connection strength with other genes. The association of the identified core modules with lung cancer has been confirmed by pathway and gene ontology enrichment analysis.

Biclustering algorithms are essential for processing gene expression data. However, to process the dataset, most biclustering algorithms require preprocessing the data matrix into a binary matrix. Regrettably, this type of preprocessing may introduce noise or cause information loss in the binary matrix, which would reduce the biclustering algorithm's ability to effectively obtain the optimal biclusters. In this paper, we propose a new preprocessing method named Mean-Standard Deviation (MSD) to resolve the problem. Additionally, we introduce a new biclustering algorithm called Weight Adjacency Difference Matrix Binary Biclustering (W-AMBB) to effectively process datasets containing overlapping biclusters. The basic idea is to create a weighted adjacency difference matrix by applying weights to a binary matrix that is derived from the data matrix. This allows us to identify genes with significant associations in sample data by efficiently identifying similar genes that respond to specific conditions. Furthermore, the performance of the W-AMBB algorithm was tested on both synthetic and real datasets and compared with other classical biclustering methods. The experiment results demonstrate that the W-AMBB algorithm is significantly more robust than the compared biclustering methods on the synthetic dataset. Additionally, the results of the GO enrichment analysis show that the W-AMBB method possesses biological significance on real datasets.

An Increase in microbial activity is shown to be intimately connected with the pathogenesis of diseases. Considering the expense of traditional verification methods, researchers are working to develop high-efficiency methods for detecting potential disease-related microbes. In this article, a new prediction method, MSF-LRR, is established, which uses Low-Rank Representation (LRR) to perform multi-similarity information fusion to predict disease-related microbes. Considering that most existing methods only use one class of similarity, three classes of microbe and disease similarity are added. Then, LRR is used to obtain low-rank structural similarity information. Additionally, the method adaptively extracts the local low-rank structure of the data from a global perspective, to make the information used for the prediction more effective. Finally, a neighbor-based prediction method that utilizes the concept of collaborative filtering is applied to predict unknown microbe-disease pairs. As a result, the AUC value of MSF-LRR is superior to other existing algorithms under 5-fold cross-validation. Furthermore, in case studies, excluding originally known associations, 16 and 19 of the top 20 microbes associated with Bacterial Vaginosis and Irritable Bowel Syndrome, respectively, have been confirmed by the recent literature. In summary, MSF-LRR is a good predictor of potential microbe-disease associations and can contribute to drug discovery and biological research.

Single-cell RNA sequencing (scRNA-Seq) technology has emerged as a powerful tool to investigate cellular heterogeneity within tissues, organs, and organisms. One fundamental question pertaining to single-cell gene expression data analysis revolves around the identification of cell types, which constitutes a critical step within the data processing workflow. However, existing methods for cell type identification through learning low-dimensional latent embeddings often overlook the intercellular structural relationships. In this paper, we present a novel non-negative low-rank similarity correction model (NLRSIM) that leverages subspace clustering to preserve the global structure among cells. This model introduces a novel manifold learning process to address the issue of imbalanced neighbourhood spatial density in cells, thereby effectively preserving local geometric structures. This procedure utilizes a position-sensitive hashing algorithm to construct the graph structure of the data. The experimental results demonstrate that the NLRSIM surpasses other advanced models in terms of clustering effects and visualization experiments. The validated effectiveness of gene expression information after calibration by the NLRSIM model has been duly ascertained in the realm of relevant biological studies. The NLRSIM model offers unprecedented insights into gene expression, states, and structures at the individual cellular level, thereby contributing novel perspectives to the field.

With the development of bioinformatics, the important role played by lncRNAs in various intractable diseases has aroused the interest of many experts. In recent studies, researchers have found that several human diseases are related to lncRANs. Moreover, it is very difficult and expensive to explore the unknown lncRNA-disease associations (LDAs), so only a few associations have been confirmed. It is vital to find a more accurate and effective method to identify potential LDAs. In this study, a method of collaborative matrix factorization based on correntropy (LDCMFC) is proposed for the identification of potential LDAs. To improve the robustness of the algorithm, the traditional minimization of the Euclidean distance is replaced with the maximized correntropy. In addition, the weighted K nearest known neighbor (WKNKN) method is used to rebuild the adjacency matrix. Finally, the performance of LDCMFC is tested by 5-fold cross-validation. Compared with other traditional methods, LDACMFC obtains a higher AUC of 0.8628. In different types of studies of three important cancer cases, most of the potentially relevant lncRNAs derived from the experiments have been validated in the databases. The final result shows that LDCMFC is a feasible method to predict LDAs.

MicroRNAs (miRNAs) are single-stranded small RNAs. An increasing number of studies have shown that miRNAs play a vital role in many important biological processes. However, some experimental methods to predict unknown miRNA-disease associations (MDAs) are time-consuming and costly. Only a small percentage of MDAs are verified by researchers. Therefore, there is a great need for high-speed and efficient methods to predict novel MDAs. In this paper, a new computational method based on Dual-Network Information Fusion (DNIF) is developed to predict potential MDAs. Specifically, on the one hand, two enhanced sub-models are integrated to reconstruct an effective prediction framework; on the other hand, the prediction performance of the algorithm is improved by fully fusing multiple omics data information, including validated miRNA-disease associations network, miRNA functional similarity, disease semantic similarity and Gaussian interaction profile (GIP) kernel network associations. As a result, DNIF achieves the excellent performance under situation of 5-fold cross validation (average AUC of 0.9571). In the cases study of three important human diseases, our model has achieved satisfactory performance in predicting potential miRNAs for certain diseases. The reliable experimental results demonstrate that DNIF could serve as an effective calculation method to accelerate the identification of MDAs.

Advances in omics technology have enriched the understanding of the biological mechanisms of diseases, which has provided a new approach for cancer research. Multi-omics data contain different levels of cancer information, and comprehensive analysis of them has attracted wide attention. However, limited by the dimensionality of matrix models, traditional methods cannot fully use the key high-dimensional global structure of multi-omics data. Moreover, besides global information, local features within each omics are also critical. It is necessary to consider the potential local information together with the high-dimensional global information, ensuring that the shared and complementary features of the omics data are comprehensively observed. In view of the above, this article proposes a new tensor integrative framework called the strong complementarity tensor decomposition model (BioSTD) for cancer multi-omics data. It is used to identify cancer subtype specific genes and cluster subtype samples. Different from the matrix framework, BioSTD utilizes multi-view tensors to coordinate each omics to maximize high-dimensional spatial relationships, which jointly considers the different characteristics of different omics data. Meanwhile, we propose the concept of strong complementarity constraint applicable to omics data and introduce it into BioSTD. Strong complementarity is used to explore the potential local information, which can enhance the separability of different subtypes, allowing consistency and complementarity in the omics data to be fully represented. Experimental results on real cancer datasets show that our model outperforms other advanced models, which confirms its validity.

Single-cell RNA sequencing (scRNA-seq) technology can provide expression profile of single cells, which propels biological research into a new chapter. Clustering individual cells based on their transcriptome is a critical objective of scRNA-seq data analysis. However, the high-dimensional, sparse and noisy nature of scRNA-seq data pose a challenge to single-cell clustering. Therefore, it is urgent to develop a clustering method targeting scRNA-seq data characteristics. Due to its powerful subspace learning capability and robustness to noise, the subspace segmentation method based on low-rank representation (LRR) is broadly used in clustering researches and achieves satisfactory results. In view of this, we propose a personalized low-rank subspace clustering method, namely PLRLS, to learn more accurate subspace structures from both global and local perspectives. Specifically, we first introduce the local structure constraint to capture the local structure information of the data, while helping our method to obtain better inter-cluster separability and intra-cluster compactness. Then, in order to retain the important similarity information that is ignored by the LRR model, we utilize the fractional function to extract similarity information between cells, and introduce this information as the similarity constraint into the LRR framework. The fractional function is an efficient similarity measure designed for scRNA-seq data, which has theoretical and practical implications. In the end, based on the LRR matrix learned from PLRLS, we perform downstream analyses on real scRNA-seq datasets, including spectral clustering, visualization and marker gene identification. Comparative experiments show that the proposed method achieves superior clustering accuracy and robustness.

In this study, we proposed a novel method called the graph capsule convolutional network (GCCN) to predict the progression from mild cognitive impairment to dementia and identify its pathogenesis. First, we proposed a novel risk gene discovery component to indirectly target genes with higher interactions with others. These risk genes and brain regions were collected as nodes to construct heterogeneous pathogenic information association graphs. Second, the graph capsules were established by projecting heterogeneous pathogenic information into a set of disentangled latent components. The orientation and length of capsules are representations of the format and intensity of pathogenic information. Third, graph capsule convolution network was used to model the information flows among pathogenic factors and elaborates the convergence of primary capsules to advanced capsules. The advanced capsule is a concept that organizes pathogenic information based on its consistency, and the synergistic effects of advanced capsules directed the development of the disease. Finally, discriminative pathogenic information flows were captured by a straightforward built-in interpretation mechanism, i.e., the dynamic routing mechanism, and applied to the identification of pathogenesis. GCCN has been experimentally shown to be significantly advanced on public datasets. Further experiments have shown that the pathogenic factors identified by GCCN are evidential and closely related to progressive mild cognitive impairment.

Identifying drug-disease associations (DDAs) is critical to the development of drugs. Traditional methods to determine DDAs are expensive and inefficient. Therefore, it is imperative to develop more accurate and effective methods for DDAs prediction. Most current DDAs prediction methods utilize original DDAs matrix directly. However, the original DDAs matrix is sparse, which greatly affects the prediction consequences. Hence, a prediction method based on multi-similarities graph convolutional autoencoder (MSGCA) is proposed for DDAs prediction. First, MSGCA integrates multiple drug similarities and disease similarities using centered kernel alignment-based multiple kernel learning (CKA-MKL) algorithm to form new drug similarity and disease similarity, respectively. Second, the new drug and disease similarities are improved by linear neighborhood, and the DDAs matrix is reconstructed by weighted K nearest neighbor profiles. Next, the reconstructed DDAs and the improved drug and disease similarities are integrated into a heterogeneous network. Finally, the graph convolutional autoencoder with attention mechanism is utilized to predict DDAs. Compared with extant methods, MSGCA shows superior results on three datasets. Furthermore, case studies further demonstrate the reliability of MSGCA.

The development of single-cell RNA sequencing (scRNA-seq) technology has opened up a new perspective for us to study disease mechanisms at the single cell level. Cell clustering reveals the natural grouping of cells, which is a vital step in scRNA-seq data analysis. However, the high noise and dropout of single-cell data pose numerous challenges to cell clustering. In this study, we propose a novel matrix factorization method named NLRRC for single-cell type identification. NLRRC joins non-negative low-rank representation (LRR) and random walk graph regularized NMF (RWNMFC) to accurately reveal the natural grouping of cells. Specifically, we find the lowest rank representation of single-cell samples by non-negative LRR to reduce the difficulty of analyzing high-dimensional samples and capture the global information of the samples. Meanwhile, by using random walk graph regularization (RWGR) and NMF, RWNMFC captures manifold structure and cluster information before generating a cluster allocation matrix. The cluster assignment matrix contains cluster labels, which can be used directly to get the clustering results. The performance of NLRRC is validated on simulated and real single-cell datasets. The results of the experiments illustrate that NLRRC has a significant advantage in single-cell type identification.

Studies have revealed that microbes have an important effect on numerous physiological processes, and further research on the links between diseases and microbes is significant. Given that laboratory methods are expensive and not optimized, computational models are increasingly used for discovering disease-related microbes. Here, a new neighbor approach based on two-tier Bi-Random Walk is proposed for potential disease-related microbes, known as NTBiRW. In this method, the first step is to construct multiple microbe similarities and disease similarities. Then, three kinds of microbe/disease similarity are integrated through two-tier Bi-Random Walk to obtain the final integrated microbe/disease similarity network with different weights. Finally, Weighted K Nearest Known Neighbors (WKNKN) is used for prediction based on the final similarity network. In addition, leave-one-out cross-validation (LOOCV) and 5-fold cross-validation (5-fold CV) are applied for evaluating the performance of NTBiRW. Multiple evaluating indicators are taken to show the performance from multiple perspectives. And most of the evaluation index values of NTBiRW are better than those of the compared methods. Moreover, in case studies on atopic dermatitis and psoriasis, most of the first 10 candidates in the final result can be proven. This also demonstrates the capability of NTBiRW for discovering new associations. Therefore, this method can contribute to the discovery of disease-related microbes and thus offer new thoughts for further understanding the pathogenesis of diseases.

Automatic seizure detection could facilitate early detection, improve treatment planning, and reduce medical workload. This study describes a novel Logarithmic Euclidean-Gaussian Mixture Models (LE-GMMs) and an improved Deep Forest learning algorithm for epileptic seizure detection. The LE-GMMs could map the Riemannian manifold structure of Gaussian models to linear Euclidean space, which fully exploits the ability of GMMs to distinguish non-seizure and seizure EEG signals. The Multi-Pooling and error Screening Forest (MPSForest) learning method based on Deep Forest uses multi-pooling and out-of-bagging (OOB) error screening to reduce memory load and random tree construction. Firstly, variational modal decomposition (VMD) is applied to decompose electroencephalogram (EEG) signals into five layers, and the first three layers are chosen to construct EEG time-frequency distribution. Then Gaussian Mixture Models are estimated, and the LE-GMMs are constructed to extract valid EEG features. These features are input into the MPSForest model to classify seizure and non-seizure samples. After that, the outputs are subjected to post-processing to get the final seizure detection results, including moving average filtering and the adaptive collar technique. The proposed method achieves average sensitivity of 98.22% and specificity of 98.99% on the UPenn and Mayo Clinic dataset, and for the long-term Freiburg EEG dataset with 21 patients, the sensitivity of 98.47% and specificity of 98.57% are yielded respectively with the false detection rate of 0.24/h. The experimental results show that this proposed method has excellent accuracy in distinguishing non-seizure and seizure EEG signals and holds great potential for clinical research and diagnostics.

Determining microRNA (miRNA)-disease associations (MDAs) is an integral part in the prevention, diagnosis, and treatment of complex diseases. However, wet experiments to discern MDAs are inefficient and expensive. Hence, the development of reliable and efficient data integrative models for predicting MDAs is of significant meaning. In the present work, a novel deep learning method for predicting MDAs through deep autoencoder with multiple kernel learning (DAEMKL) is presented. Above all, DAEMKL applies multiple kernel learning (MKL) in miRNA space and disease space to construct miRNA similarity network and disease similarity network, respectively. Then, for each disease or miRNA, its feature representation is learned from the miRNA similarity network and disease similarity network via the regression model. After that, the integrated miRNA feature representation and disease feature representation are input into deep autoencoder (DAE). Furthermore, the novel MDAs are predicted through reconstruction error. Ultimately, the AUC results show that DAEMKL achieves outstanding performance. In addition, case studies of three complex diseases further prove that DAEMKL has excellent predictive performance and can discover a large number of underlying MDAs. On the whole, our method DAEMKL is an effective method to identify MDAs.

Neuroimaging genetics is a powerful technique for discovering the relationships between genotype and imaging phenotype. However, many univariate or multivariate regression approaches have only focused on imaging quantitative traits (QTs) that are relevant to some genetic markers on distinct pathways and might not be disease specific. In addition, there are complex relations between subjects of distinct modalities and diagnosis labels, which contain useful information for the treatment of Alzheimer’s disease (AD). Here, a novel probability connectivity-based penalty is developed for incorporating the prior information to explore relations among different subjects with disease status. Specifically, the Pearson’s correlation coefficient (PCC) is used to construct a similarity matrix in a probability graph, first to express the connectivity weights between subjects, which can reflect the different correlations among subjects within the same class. Second, a diagnosis-aligned probability connectivity-based multimodal regression (DPCMR) method is employed to find the relations among modalities of distinct subjects. It also mines associations between genetic markers and imaging phenotypes. The AD risk single nucleotide polymorphism (SNP) APOE rs429358 and three modalities of neuroimaging data are used to verify the performance of all of the methods. The experimental results reveal that DPCMR has better performance and identifies some brain regions across multiple modalities related to diseases.

Ensemble learning is to train and combine multiple learners to complete the corresponding learning tasks. It can improve the stability of the overall model, and a good ensemble method can further improve the accuracy of the model. At the same time, as one of the outstanding representatives of machine learning, Extreme Learning Machine has attracted the continuous attention of experts and scholars. to get a better representation of the feature space, we extend the Gaussian kernel in the kernel risk-sensitive loss and propose a Kernel Risk-Sensitive Loss of q-Gaussian kernel and Hyper-graph Regularized Extreme Learning Machine method. Since the contingency in the ELM training process cannot be completely avoided, the stability of most ELM methods is affected to some extent. What’s more, we introduce the voting mechanism and a new ELM classification model named Kernel Risk-Sensitive Loss of q-Gaussian kernel and Hyper-graph Regularized Integrated Extreme Learning Machine based on Voting Mechanism is proposed. It improves the stability of the model through the idea of ensemble learning. We apply the new model on six real data sets, and through observation and analysis of experimental results, we find that the new model has certain competitiveness, especially in classification accuracy and stability.

In the genome-wide association studies (GWAS), epistasis detection is of great significance to study the pathogenesis of complex diseases. Epistasis refers to the effect of interactions between multiple single nucleotide polymorphisms (SNPs) on complex diseases. In this paper, an artificial bee colony algorithm based on self-adjusting random grouping (ABC-SRG) is proposed for high-order epistasis detection. ABC-SRG adopts a new self-adjusting random grouping strategy, which realizes the division of the original data according to the fitness value of each grouping. In addition, a variance-based adaptive iteration strategy is proposed, which implements the adaptive iteration through the variance of the fitness value of each iteration of the algorithm. To demonstrate the effectiveness of the algorithm, the experiments on simulated data and real data were conducted. In the simulation experiments, ABC-SRG was compared with the other five methods for second-order and third-order SNP interaction detection. Age-related macular degeneration (AMD) data were selected for the real data experiment, and most of the SNP interactions detected in the experiment have been confirmed to be related to the AMD disease. Therefore, ABC-SRG is an effective method to detect high-order epistasis.

Individuals with the Alzheimer’s disease (AD) go through multiple stages from health to illness. The pathogenesis of AD remains uncertain, and there may be different biomarkers in different diagnostic groups. In the field of brain imaging genetics, it has become a significance challenge to utilize the brain genotype-phenotype correlations to probe the pathogenesis of AD. To solve these problems, a novel approach named bi-multitask regularized sparse canonical correlation analysis and logistic regression (BRSCCALR) is proposed, which can identify AD related biomarkers and classify subjects. Specifically, multitask sparse canonical correlation analysis focuses on learning genotype-phenotype associations. Yet the newly constructed multitask regularized logistic regression that prevents overfitting is responsible for identifying diagnosis-specific biomarkers. In addition, the connectivity-based penalty term is also introduced to enrich the prior information and enhance the biological significance of the method. Under the five-fold cross-validation experiment, the proposed method is compared with several state-of-the-art methods on a real brain imaging genetic dataset. The canonical correlation coefficients demonstrate that BRSCCALR method achieves outstanding performance. Finally, the learned biomarkers are applied to the classification experiment, and results show that the biomarkers are valid.

It is well known that the study of the lncRNA-disease associations (LDAs) is of great value for the diagnosis and cure of many complex diseases. However, exploring unknown LDAs is extremely difficult and expensive. Therefore, it is essential to find a more accurate and effective calculation method to predict the potential LDAs. However, most previous studies focused on designing complex similarity-based methods to predict the potential interaction between lncRNAs and diseases. In this research, combining the three biological networks of lncRNA-disease, miRNA-lncRNA and miRNA-disease, a new computing model based on heterogeneous networks and stacked autoencoder (SAE) is proposed, called HSAELDA. Then, the SAE is used to extract the comprehensive features of the lncRNA-disease pairs, the LightGBM classifier is used for training. At the same time, five-fold cross-validation (CV) is used to compare our model with some existing prediction methods. The final comparison results showed HSAELDA obtained the highest AUC value of 0.978. In conclusion, the overall prediction performance of HSAELDA has been greatly improved compared to the state-of-art models. Experimental results and case study results show that HSAELDA is an effective method for predicting potential LDAs.

Accurate identification of cancer driver modules or pathways is important for controlling disease progression and timely treatment. In recent years, most approaches have been based on mutation data combined with gene interaction networks to identify cancer driver modules, but cancer-related genes tend to interact with each other, and the mutations they experience disruption their neighbors. Therefore, we propose a framework that combines network function and topological information to quantify the extent to which mutated genes disrupt their neighbors. Firstly, similarity in protein-protein interaction networks binds to high coverage and high mutual exclusivity of mutant genes, which are used to obtain the impact of the interaction between two mutant genes on biological function. Secondly, we quantified the degree of gene disruption by mutant genes in their neighborhood using an adaptive spread strength measure to obtain the gene spread strength network (GSSN). Finally, the module is extended using CFinder strategy to obtain the optimal driving module. We apply our method to 12 cancer datasets, and the experimental results show that our method outperforms the other three methods on most datasets. At the same time, we also analyze common and low-frequency driver modules in cancer.

The mining and analysis of genomics data provides a new idea for exploring the pathogenesis of human disease. Since these data often have the features of small samples, high-dimensional, and high redundancy, the traditional matrix decomposition method cannot fully mine the spatial structure and multiple perspective information of cancer genomics data. Inspired by the recently proposed robust tensor completion method, a tensor robust PCA method (TTTD) was proposed based on U-product and transformed tensor singular value decomposition (t-SVD) to explore the integrated cancer genomics data in this paper. Specifically, the unitary transform matrix is employed to replace the discrete Fourier transform matrix in t-SVD, which contributes to recover a lower tubal rank tensor to a certain extent. Meanwhile, the $\mathrm{L}_{2,1}-$norm is employed to learn the sparse term, and the row sparse constraint generated by it can better detect the abnormal value of the real tensor. In addition, the alternating direction method of the multiplier algorithm is used to optimize the TTTD method. Experimental results on the three integrated cancer multi-omics datasets show that the TTTD method achieves the better performance.

With the development of research on the complex aetiology of many diseases, computational drug repositioning methodology has proven to be a shortcut to costly and inefficient traditional methods. Therefore, developing more promising computational methods is indispensable for finding new candidate diseases to treat with existing drugs. In this paper, a model integrating a new variant of message passing neural network and a novel-gated fusion mechanism called GLGMPNN is proposed for drug-disease association prediction. First, a light-gated message passing neural network (LGMPNN), including message passing, aggregation and updating, is proposed to separately extract multiple pieces of information from the similarity networks and the association network. Then, a gated fusion mechanism consisting of a forget gate and an output gate is applied to integrate the multiple pieces of information to extent. The forget gate calculated by the multiple embeddings is built to integrate the association information into the similarity information. Furthermore, the final node representations are controlled by the output gate, which fuses the topology information of the networks and the initial similarity information. Finally, a bilinear decoder is adopted to reconstruct an adjacency matrix for drug-disease associations. Evaluated by 10-fold cross-validations, GLGMPNN achieves excellent performance compared with the current models. The following studies show that our model can effectively discover novel drug-disease associations.

Biclustering algorithm is an effective tool for processing gene expression datasets. There are two kinds of data matrices, binary data and non-binary data, which are processed by biclustering method. A binary matrix is usually converted from pre-processed gene expression data, which can effectively reduce the interference from noise and abnormal data, and is then processed using a biclustering algorithm. However, biclustering algorithms of dealing with binary data have a poor balance between running time and performance. In this paper, we propose a new biclustering algorithm called the Adjacency Difference Matrix Binary Biclustering algorithm (AMBB) for dealing with binary data to address the drawback. The AMBB algorithm constructs the adjacency matrix based on the adjacency difference values, and the submatrix obtained by continuously updating the adjacency difference matrix is called a bicluster. The adjacency matrix allows for clustering of gene that undergo similar reactions under different conditions into clusters, which is important for subsequent genes analysis. Meanwhile, experiments on synthetic and real datasets visually demonstrate that the AMBB algorithm has high practicability.

Extracting genes involved in cancer lesions from gene expression data is critical for cancer research and drug development. The method of feature selection has attracted much attention in the field of bioinformatics. Principal Component Analysis (PCA) is a widely used method for learning low-dimensional representation. Some variants of PCA have been proposed to improve the robustness and sparsity of the algorithm. However, the existing methods ignore the high-order relationships between data. In this paper, a new model named Robust Principal Component Analysis via Hypergraph Regularization (HRPCA) is proposed. In detail, HRPCA utilizes L2,1-norm to reduce the effect of outliers and make data sufficiently row-sparse. And the hypergraph regularization is introduced to consider the complex relationship among data. Important information hidden in the data are mined, and this method ensures the accuracy of the resulting data relationship information. Extensive experiments on multi-view biological data demonstrate that the feasible and effective of the proposed approach.

The rapid development of single-cell RNA sequencing (scRNA-seq)technology reveals the gene expression status and gene structure of individual cells, reflecting the heterogeneity and diversity of cells. The traditional methods of scRNA-seq data analysis treat data as the same subspace, and hide structural information in other subspaces. In this paper, we propose a low-rank subspace ensemble clustering framework (LRSEC)to analyze scRNA-seq data. Assuming that the scRNA-seq data exist in multiple subspaces, the low-rank model is used to find the lowest rank representation of the data in the subspace. It is worth noting that the penalty factor of the low-rank kernel function is uncertain, and different penalty factors correspond to different low-rank structures. Moreover, the single cluster model is difficult to find the cellular structure of all datasets. To strengthen the correlation between model solutions, we construct a new ensemble clustering framework LRSEC by using the low-rank model as the basic learner. The LRSEC framework captures the global structure of data through low-rank subspaces, which has better clustering performance than a single clustering model. We validate the performance of the LRSEC framework on seven small datasets and one large dataset and obtain satisfactory results.

A growing number of clinical studies have provided substantial evidence of a close relationship between the microbe and the disease. Thus, it is necessary to infer potential microbe-disease associations. But traditional approaches use experiments to validate these associations that often spend a lot of materials and time. Hence, more reliable computational methods are expected to be applied to predict disease-associated microbes. In this article, an innovative mean for predicting microbe-disease associations is proposed, which is based on network consistency projection and label propagation (NCPLP). Given that most existing algorithms use the Gaussian interaction profile (GIP) kernel similarity as the similarity criterion between microbe pairs and disease pairs, in this model, Medical Subject Headings descriptors are considered to calculate disease semantic similarity. In addition, 16S rRNA gene sequences are borrowed for the calculation of microbe functional similarity. In view of the gene-based sequence information, we use two conventional methods (BLAST+ and MEGA7) to assess the similarity between each pair of microbes from different perspectives. Especially, network consistency projection is added to obtain network projection scores from the microbe space and the disease space. Ultimately, label propagation is utilized to reliably predict microbes related to diseases. NCPLP achieves better performance in various evaluation indicators and discovers a greater number of potential associations between microbes and diseases. Also, case studies further confirm the reliable prediction performance of NCPLP. To conclude, our algorithm NCPLP has the ability to discover these underlying microbe-disease associations and can provide help for biological study.

Cancer genome data generally consists of multiple views from different sources. These views provide different levels of information about gene activity, as well as more comprehensive cancer information. The low-rank representation (LRR) method, as a powerful subspace clustering method, has been extended and applied in cancer data research. Although the multi-view learning methods based on low rank representation have achieved good results in cancer multi-omics analysis because they fully consider the consistency and complementarity between views, these methods have some shortcomings in mining the potential local geometry of data. In view of this, this paper proposes a new method named Multi-view Random-walk Graph regularization Low-Rank Representation (MRGLRR) to comprehensively analyze multi-view genomics data. This method uses multi-view model to find the common centroid of view. By constructing a joint affinity matrix to learn the low-rank subspace representation of multiple sets of data, the hidden information of each view is fully obtained. In addition, this method introduces random walk graph regularization constraint to obtain more accurate similarity between samples. Different from the traditional graph regularization constraint, after constructing the KNN graph, we use the random walk algorithm to obtain the weight matrix. The random walk algorithm can retain more local geometric information and better learn the topological structure of the data. What's more, a feature gene selection strategy suitable for multi-view model is proposed to find more differentially expressed genes with research value. Experimental results show that our method is better than other representative methods in terms of clustering and feature gene selection for cancer multi-omics data.

The exploration of single cell RNA-sequencing (scRNA-seq) technology generates a new perspective to analyze biological problems. One of the major applications of scRNA-seq data is to discover subtypes of cells by cell clustering. Nevertheless, it is challengeable for traditional methods to handle scRNA-seq data with high level of technical noise and notorious dropouts. To better analyze single cell data, a novel scRNA-seq data analysis model called Maximum correntropy criterion based Non-negative and Low Rank Representation (MccNLRR) is introduced. Specifically, the maximum correntropy criterion, as an effective loss function, is more robust to the high noise and large outliers existed in the data. Moreover, the low rank representation is proven to be a powerful tool for capturing the global and local structures of data. Therefore, some important information, such as the similarity of cells in the subspace, is also extracted by it. Then, an iterative algorithm on the basis of the half-quadratic optimization and alternating direction method is developed to settle the complex optimization problem. Before the experiment, we also analyze the convergence and robustness of MccNLRR. At last, the results of cell clustering, visualization analysis, and gene markers selection on scRNA-seq data reveal that MccNLRR method can distinguish cell subtypes accurately and robustly.

The development of single-cell RNA sequencing (scRNA-seq) technology has made it possible to measure gene expression levels at the resolution of a single cell, which further reveals the complex growth processes of cells such as mutation and differentiation. Recognizing cell heterogeneity is one of the most critical tasks in scRNA-seq research. To solve it, we propose a non-negative matrix factorization framework based on multi-subspace cell similarity learning for unsupervised scRNA-seq data analysis (MscNMF). MscNMF includes three parts: data decomposition, similarity learning, and similarity fusion. The three work together to complete the data similarity learning task. MscNMF can learn the gene features and cell features of different subspaces, and the correlation and heterogeneity between cells will be more prominent in multi-subspaces. The redundant information and noise in each low-dimensional feature space are eliminated, and its gene weight information can be further analyzed to calculate the optimal number of subpopulations. The final cell similarity learning will be more satisfactory due to the fusion of cell similarity information in different subspaces. The advantage of MscNMF is that it can calculate the number of cell types and the rank of Non-negative matrix factorization (NMF) reasonably. Experiments on eight real scRNA-seq datasets show that MscNMF can effectively perform clustering tasks and extract useful genetic markers. To verify its clustering performance, the framework is compared with other latest clustering algorithms and satisfactory results are obtained. The code of MscNMF is free available for academic (https://github.com/wangchuanyuan1/project-MscNMF).

Single-cell clustering is a crucial task of scRNA-seq analysis, which reveals the natural grouping of cells. However, due to the high noise and high dimension in scRNA-seq data, how to effectively and accurately identify cell types from a great quantity of cell mixtures is still a challenge. Considering this, in this paper, we propose a novel subspace clustering algorithm termed SLRRSC. This method is developed based on the low-rank representation model, and it aims to capture the global and local properties inherent in data. In order to make the LRR matrix describe the spatial relationship of samples more accurately, we introduce the manifold-based graph regularization and similarity constraint into the LRR-based method SLRRSC. The graph regularization can preserve the local geometric structure of the data in low-rank decomposition, so that the low-rank representation matrix contains more local structure information. By imposing similarity constraint on the low-rank matrix, the similarity information between sample pairs is further introduced into the SLRRSC model to improve the learning ability of low-rank method for global structure. At the same time, the similarity constraint makes the low-rank representation matrix symmetric, which makes it better interpretable in clustering application. We compare the effectiveness of the SLRRSC algorithm with other single-cell clustering methods on simulated data and real single-cell datasets. The results show that this method can obtain more accurate sample similarity matrix and effectively solve the problem of cell type recognition.

Non-negative Matrix Factorization (NMF) as a powerful dimension reduction tool, which is widely used in the bioinformatics field. However, the loss function of conventional NMF is sensitive to non-Gaussian noise and outliers. In addition, NMF-based algorithm overlooks the geometric structure of high dimensional data. To improve the robustness of NMF, we propose a novel method called Sparse Hyper-graph regularized Non-negative Matrix Factorization by Maximizing Correntropy (SHNMF-MCC) in this paper. Specifically, the maximum correntropy criterion replaces the Euclidean distance in the loss term of SHNMF-MCC, which can filter out the noise with large outliers. Moreover, the high-order geometric structure in more sample points is completely preserved in the low-dimensional manifold through the hyper-graph regularization. Meanwhile, the sparse constraint is applied to the loss function to reduce matrix complexity and analysis difficulty. Then, the complex optimization problem can be solved by a half-quadratic (HQ) optimization approach. Before carrying out experiments, we analyze the convergence of SHNMF-MCC. Sample clustering experiments on The Cancer Genome Atlas (TCGA) data and single cell RNA-sequencing (scRNA-seq) data verify that the proposed method is more robust and effective than other similar robust approaches.

The analysis of biological sequencing data can provide significant support for researchers to unravel the mysteries of life further. This paper proposes a robust tensor data analysis method based on correntropy and tensor singular value decomposition (t-SVD) (CoTD) to analyze high-dimensional and multi-way cancer genomics data. CoTD uses the maximum correntropy criterion to increase the sparsity of the sparse tensor and fully exploits the vital information of the tensor data. It can effectively suppress outliers in the process of recovering low-rank and separating sparse data. In addition, through t-SVD, the internal spatial structure of the original tensor data can be well preserved. In this way, essential information can be retained in the low-rank part, which increases the clustering effect. The CoTD model is optimized by the half-quadratic technique and alternating direction method of multipliers (ADMM). Sample clustering and differentially expressed gene (DEG) extraction experiments are carried out on cancer genomics datasets. CoTD model is compared with four similar methods, which proves that the CoTD model has good performance.

An important purpose of single-cell RNA sequencing (scRNA-seq) data research is to explain the complex and diverse heterogeneity information between cells, which can further deepen human understanding of the mechanisms of life and the organization of organisms. However, the high dimensionality and noise are two major factors that hinder the development of scRNA-seq data mining. Therefore, in this paper, an adaptive total-variant joint learning model (JL-ATV) is proposed to overcome these two drawbacks of scRNA-seq data mining. On the one hand, in this model, dimensionality reduction learning and segmentation reconstruction subspace methods is combined to obtain effective features descriptions of the scRNAseq data and improve the interpretability and accuracy of cell identification. On the other hand, a gradient-based learning approach, namely adaptive total variation (ATV), is applied to scRNA-seq data to preserve the internal structure and overcome the interference of noise. Finally, experiments on multiple datasets show that the JL-ATV model can obtain a set of effective features and further improve the accuracy of identifying cell types.

MOTIVATION: For network-assisted analysis, which has become a popular method of data mining, network construction is a crucial task. Network construction relies on the accurate quantification of direct associations among variables. The existence of multiscale associations among variables presents several quantification challenges, especially when quantifying nonlinear direct interactions. RESULTS: In this study, the multiscale part mutual information (MPMI), based on part mutual information (PMI) and nonlinear partial association (NPA), was developed for effectively quantifying nonlinear direct associations among variables in networks with multiscale associations. First, we defined the MPMI in theory and derived its five important properties. Second, an experiment in a three-node network was carried out to numerically estimate its quantification ability under two cases of strong associations. Third, experiments of the MPMI and comparisons with the PMI, NPA and conditional mutual information were performed on simulated datasets and on datasets from DREAM challenge project. Finally, the MPMI was applied to real datasets of glioblastoma and lung adenocarcinoma to validate its effectiveness. Results showed that the MPMI is an effective alternative measure for quantifying nonlinear direct associations in networks, especially those with multiscale associations. AVAILABILITY AND IMPLEMENTATION: The source code of MPMI is available online at https://github.com/CDMB-lab/MPMI. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: In the development of science and technology, there are increasing evidences that there are some associations between lncRNAs and human diseases. Therefore, finding these associations between them will have a huge impact on our treatment and prevention of some diseases. However, the process of finding the associations between them is very difficult and requires a lot of time and effort. Therefore, it is particularly important to find some good methods for predicting lncRNA-disease associations (LDAs). RESULTS: -norm is added in our method. At the same time, Gaussian interaction profile kernel is added to our method, which increase the network similarity between lncRNA and disease. Finally, the AUC value obtained by the experiment is used to evaluate the quality of our method, and the AUC value is obtained by the ten-fold cross-validation method. CONCLUSIONS: The AUC value obtained by the DSCMF method is 0.8523. At the end of the paper, simulation experiment is carried out, and the experimental results of prostate cancer, breast cancer, ovarian cancer and colorectal cancer are analyzed in detail. The DSCMF method is expected to bring some help to lncRNA-disease associations research. The code can access the https://github.com/Ming-0113/DSCMF website.

BACKGROUND: With the rapid development of various advanced biotechnologies, researchers in related fields have realized that microRNAs (miRNAs) play critical roles in many serious human diseases. However, experimental identification of new miRNA-disease associations (MDAs) is expensive and time-consuming. Practitioners have shown growing interest in methods for predicting potential MDAs. In recent years, an increasing number of computational methods for predicting novel MDAs have been developed, making a huge contribution to the research of human diseases and saving considerable time. In this paper, we proposed an efficient computational method, named bipartite graph-based collaborative matrix factorization (BGCMF), which is highly advantageous for predicting novel MDAs. RESULTS: By combining two improved recommendation methods, a new model for predicting MDAs is generated. Based on the idea that some new miRNAs and diseases do not have any associations, we adopt the bipartite graph based on the collaborative matrix factorization method to complete the prediction. The BGCMF achieves a desirable result, with AUC of up to 0.9514 ± (0.0007) in the five-fold cross-validation experiments. CONCLUSIONS: Five-fold cross-validation is used to evaluate the capabilities of our method. Simulation experiments are implemented to predict new MDAs. More importantly, the AUC value of our method is higher than those of some state-of-the-art methods. Finally, many associations between new miRNAs and new diseases are successfully predicted by performing simulation experiments, indicating that BGCMF is a useful method to predict more potential miRNAs with roles in various diseases.

BACKGROUND: Identifying lncRNA-disease associations not only helps to better comprehend the underlying mechanisms of various human diseases at the lncRNA level but also speeds up the identification of potential biomarkers for disease diagnoses, treatments, prognoses, and drug response predictions. However, as the amount of archived biological data continues to grow, it has become increasingly difficult to detect potential human lncRNA-disease associations from these enormous biological datasets using traditional biological experimental methods. Consequently, developing new and effective computational methods to predict potential human lncRNA diseases is essential. RESULTS: Using a combination of incremental principal component analysis (IPCA) and random forest (RF) algorithms and by integrating multiple similarity matrices, we propose a new algorithm (IPCARF) based on integrated machine learning technology for predicting lncRNA-disease associations. First, we used two different models to compute a semantic similarity matrix of diseases from a directed acyclic graph of diseases. Second, a characteristic vector for each lncRNA-disease pair is obtained by integrating disease similarity, lncRNA similarity, and Gaussian nuclear similarity. Then, the best feature subspace is obtained by applying IPCA to decrease the dimension of the original feature set. Finally, we train an RF model to predict potential lncRNA-disease associations. The experimental results show that the IPCARF algorithm effectively improves the AUC metric when predicting potential lncRNA-disease associations. Before the parameter optimization procedure, the AUC value predicted by the IPCARF algorithm under 10-fold cross-validation reached 0.8529; after selecting the optimal parameters using the grid search algorithm, the predicted AUC of the IPCARF algorithm reached 0.8611. CONCLUSIONS: We compared IPCARF with the existing LRLSLDA, LRLSLDA-LNCSIM, TPGLDA, NPCMF, and ncPred prediction methods, which have shown excellent performance in predicting lncRNA-disease associations. The compared results of 10-fold cross-validation procedures show that the predictions of the IPCARF method are better than those of the other compared methods.

Electroencephalogram (EEG) plays an important role in recording brain activity to diagnose epilepsy. However, it is not only laborious, but also not very cost effective for medical experts to manually identify the features on EEG. Therefore, automatic seizure detection in accordance with the EEG recordings is significant for the diagnosis and treatment of epilepsy. Here, a new method for detecting seizures using tensor distance (TD) is proposed. First, the time-frequency characteristics of EEG signals are obtained by wavelet transformation, and the tensor representation of EEG signals is then obtained. Tucker decomposition is used to obtain the principal components of the EEG tensor. After, the distances between different categories of EEG tensors are calculated as the EEG features. Finally, the TD features are classified through the Bayesian Linear Discriminant Analysis (Bayesian LDA) classifier. The performance of this method is measured by the sensitivity, specificity, and recognition accuracy. Results indicate 95.12% sensitivity, 97.60% specificity, 97.60% recognition accuracy, and a false detection rate of 0.76 per hour in the invasive EEG dataset, which included 566.57[Formula: see text]h of EEG recording data from 21 patients. Taken together, the results show that TD has a good detection effect for seizure classification and that this method has high computational speed and great potential for real-time diagnosis.

The identification of differentially expressed genes plays an increasingly important role biologically. Therefore, the feature selection approach has attracted much attention in the field of bioinformatics. The most popular method of principal component analysis studies two-dimensional data without considering the spatial geometric structure of the data. The recently proposed tensor robust principal component analysis method performs sparse and low-rank decomposition on three-dimensional tensors and effectively preserves the spatial structure. Based on this approach, the$L_{2,1}$- norm regularization term is introduced into the DSTPCA (Double-Sparse Constrained Tensor Principal Component Analysis) method. The DSTPCA method removes the redundant noise by double sparse constraints on the objective function to obtain sufficiently sparse results. After the regularization norm is introduced into the model, the ADMM (alternating direction method of multipliers) algorithm is used to solve the optimal problem. In the experiment of feature selection, while the more redundant genes were filtered out, the more genes closely associated with disease were screened. Experimental results using different datasets indicate that our method outperforms other methods.

Non-negative matrix factorization (NMF) is a dimensionality reduction technique based on high-dimensional mapping. It can learn part-based representations effectively. In this paper, we propose a method called Dual Hyper-graph Regularized Supervised Non-negative Matrix Factorization (HSNMF). To encode the geometric information of the data, the hyper-graph is introduced into the model as a regularization term. The advantage of hyper-graph learning is to find higher order data relationship to enhance data relevance. This method constructs the data hyper-graph and the feature hyper-graph to find the data manifold and the feature manifold simultaneously. The application of hyper-graph theory in cancer datasets can effectively find pathogenic genes. The discrimination information is further introduced into the objective function to obtain more information about the data. Supervised learning with label information greatly improves the classification effect. Furthermore, the real datasets of cancer usually contain sparse noise, so the$L_{2,1}$-norm is applied to enhance the robustness of HSNMF algorithm. Experiments under The Cancer Genome Atlas (TCGA) datasets verify the feasibility of the HSNMF method.

Protein fold recognition is one of the most essential steps for protein structure prediction, aiming to classify proteins into known protein folds. There are two main computational approaches: one is the template-based method based on the alignment scores between query-template protein pairs and the other is the machine learning method based on the feature representation and classifier. These two approaches have their own advantages and disadvantages. Can we combine these methods to establish more accurate predictors for protein fold recognition? In this study, we made an initial attempt and proposed two novel algorithms: TSVM-fold and ESVM-fold. TSVM-fold was based on the Support Vector Machines (SVMs), which utilizes a set of pairwise sequence similarity scores generated by three complementary template-based methods, including HHblits, SPARKS-X, and DeepFR. These scores measured the global relationships between query sequences and templates. The comprehensive features of the attributes of the sequences were fed into the SVMs for the prediction. Then the TSVM-fold was further combined with the HHblits algorithm so as to improve its generalization ability. The combined method is called ESVM-fold. Experimental results in two rigorous benchmark datasets (LE and YK datasets) showed that the proposed methods outperform some state-of-the-art methods, indicating that the TSVM-fold and ESVM-fold are efficient predictors for protein fold recognition.

As is known to all, constructing experiments to predict unknown miRNA-disease association is time-consuming, laborious and costly. Accordingly, new prediction model should be conducted to predict novel miRNA-disease associations. What's more, the performance of this method should be high and reliable. In this paper, a new computation model Logistic Weighted Profile-based Collaborative Matrix Factorization (LWPCMF) is put forward. In this method, weighted profile (WP) is combined with collaborative matrix factorization (CMF) to increase the performance of this model. And, the neighbor information is considered. In addition, logistic function is applied to miRNA functional similarity matrix and disease semantic similarity matrix to extract valuable information. At the same time, by adding WP and logistic function, the known correlation can be protected. And, Gaussian Interaction Profile (GIP) kernels of miRNAs and diseases are added to miRNA functional similarity network and disease semantic similarity network to augment kernel similarities. Then, a five-fold cross validation is implemented to evaluate the predictive ability of this method. Besides, case studies are conducted to view the experimental results. The final result contains not only known associations but also newly predicted ones. And, the result proves that our method is better than other existing methods. This model is able to predict potential miRNA-disease associations.

Non-negative matrix factorization (NMF) has become one of the most powerful methods for clustering and feature selection. However, the performance of the traditional NMF method severely degrades when the data contain noises and outliers or the manifold structure of the data is not taken into account. In this article, a novel method called correntropy-based hypergraph regularized NMF (CHNMF) is proposed to solve the above problem. Specifically, we use the correntropy instead of the Euclidean norm in the loss term of CHNMF, which will improve the robustness of the algorithm. And the hypergraph regularization term is also applied to the objective function, which can explore the high-order geometric information in more sample points. Then, the half-quadratic (HQ) optimization technique is adopted to solve the complex optimization problem of CHNMF. Finally, extensive experimental results on multi-cancer integrated data indicate that the proposed CHNMF method is superior to other state-of-the-art methods for clustering and feature selection.

As we all know, science and technology are developing faster and faster. Many experts and scholars have demonstrated that human diseases are related to lncRNA, but only a few associations have been confirmed, and many unknown associations need to be found. In the process of finding associations, it takes a lot of time, so finding an efficient way to predict the associations between lncRNAs and diseases is particularly important. In this paper, we propose a multi-label fusion collaborative matrix factorization (MLFCMF) approach for predicting lncRNA-disease associations (LDAs). Firstly, the lncRNA space and disease space are optimized by multi-label to enhance the intrinsic link between lncRNA and disease and to tap potential information. Multi-label learning can encode a variety of data information from the sample space. Secondly, to learn multi-label information in the data space, the fusion method is used to handle the relationship between multiple labels. More comprehensive information will be obtained by weighing the effects of different labels. The addition of Gaussian interaction profile (GIP) kernel can increase the network similarity. Finally, the lncRNA-disease associations are predicted by the method of collaborative matrix factorization. The ten-fold cross-validation method is used to evaluate the MLFCMF method, and our method finally obtains an AUC value of 0.8612. Detailed analysis of ovarian cancer, colorectal cancer, and lung cancer in the simulation experiment results. So it can be seen that our method MLFCMF is an effective model for predicting lncRNA-disease associations.

In recent years, many human diseases have been determined to be associated with certain lncRNAs. Only a small percentage of all lncRNA-disease associations (LDAs) have been discovered by researchers. Predicting novel LDAs is time-consuming and costly. It is crucial to propose a method that can effectively identify potential LDAs to solve this problem based on the available datasets. Although some current methods can effectively predict potential LDAs, the prediction accuracy needs to be improved, and there are few known associations. Moreover, there are notable errors in the method of constructing the network and the bipartite graph, which interfere with the final results. A weighted graph regularized collaborative matrix factorization (WGRCMF) method is proposed to predict novel LDAs. We introduce the graph regularization terms into the collaborative matrix factorization. Considering that manifold learning can recover low-dimensional manifold structures from high-dimensional sampled data, we can find low-dimensional manifolds in high-dimensional space. In addition, a weight matrix is also introduced into the method, the significance of which is to prevent unknown associations from contributing to the final prediction matrix. Finally, the prediction accuracy of this method is better than those of other methods. In several cancer cases, we implemented the corresponding simulation experiments. According to the experimental results, the proposed method is feasible and effective.

In recent years, single-cell RNA sequencing (scRNA-seq) technology has made significant progress in many fields and become an important means to study cell dynamics. How to effectively mine valuable biological information from these sequencing data is a topic worthy of researching. In this paper, two new methods based on traditional principal component analysis (PCA) are proposed and used to scRNA-seq data. The first method named dual graph regularized PCA (DGPPCA) is based on Frobenius-norm and L2,p-norm constraints, and the method named the dual graph-regularization PCA (DG2PPCA) is based on the nonconvex proximal Lp-norm ( 02,p-norm constraints. We apply these two new methods to five scRNA-seq datasets, and perform bi-clustering on genes and samples at the same time. Extensive experiments are conducted to explore the influence of the combination of different norm constraints in the two optimization models.

The rapid development of single cell RNA sequencing (scRNA-seq) has made it possible to study the association between cells and genes at molecular resolution. When the follow-up analysis is carried out, it is often difficult to extract the cell information in high-dimensional space because of the high gene dimension in single-cell sequencing, which leads to inaccurate results in the follow-up analysis. To solve the problem, we propose a method called locally manifold non-negative matrix factorization based on centroid for scRNA-seq data analysis (MNMFC). MNMFC is a similarity modeling scheme based on locally manifold, which can map cell association in high dimensional space. Through similarity learning based on locally manifold and non-negative matrix decomposition (NMF) algorithm, the data in high-dimensional space can be mapped to low-dimensional space, which provides help for downstream clustering analysis. The performance of the model was validated experimentally on 10 scRNA-seq datasets. Compared with other nine advanced single-cell clustering methods, whether it is a comprehensive analysis or an individual analysis of the dataset, MNMFC has achieved encouraging results.

Genetic information becomes more and more important in the process of biological research. Gene analysis is an effective mean in biological research, especially the analysis of differentially expressed genes. Robust principal component analysis (RPCA) is an effective method to identify differentially expressed genes. But tensor robust principal component analysis (TRPCA) performs better than RPCA when processing multi-dimensional data. The traditional TRPCA method also has limitations in restoring low-rank sparse components. To further improve the accuracy of the TRPCA method in restoring low-rank components and sparse components, we propose a novel TRPCA method to obtain high-order correlations information of multi-dimensional data. It uses a new nuclear norm based on t-product operator to approximate the rank function. The L2,1-norm is used to improve the sparsity of tensors and reduce the negative effects caused by noises and outliers. At the same time, the introduction of L2,1-norm enhances the sparsity of error components, and improves the accuracy of low-rank component recovery. The low-rank sparse components are obtained by solving the convex problem of the new tensor nuclear norm. It can well preserve the spatial structure and make full use of complementary information to improve the clustering effect. Alternating direction method of multiplier (ADMM) is used to solve the optimization problem of this method. Experimental results on different cancer genomic datasets indicate that our method is superior to other methods.

Reliable epileptic seizure prediction is significantly important in improving the life of patients and enhancing the therapy effect. In this paper, a novel seizure prediction algorithm is proposed employing the tensor decomposition on long-term intracranial EEG recordings. The modified Stockwell transform (MST) is conducted on the segmented EEG signals to transform into two-dimensional instantaneous power spectra. Then, the third-order tensor representation of the multi-channel EEG signals are structured with the models of time, frequency and space. Tucker decomposition, one valid tensor decomposition method, is applied to obtain the principal components of the EEG tensors and the smaller core tensors after decomposition are extracted as features of interictal EEG and preictal EEG. After that, the classification of preictal and interictal data is achieved by feeding the features into Bayesian Linear Discriminant Analysis (BLDA) classifier. The evaluation of the proposed algorithm is carried out on the Freiburg EEG database and a sensitivity of 88.49% for the seizure occurrence period of 30 min, meanwhile, a sensitivity of 97.62% for the seizure occurrence period of 50 min are yielded with a false alarm rate of 0. 25/h. The results show that this algorithm based on tensor analysis has notable performance for seizure prediction.

With the rapid development of the next-generation sequencing technology, a large amount of genomics information has been obtained. The scale of biological sequencing data is particularly large and complex. The tensor robust principal component analysis (TRPCA) method can effectively preserve the spatial structure of tensor data, so it has received extensive attention. However, the low-rank tensor obtained by TRPCA may be damaged to a certain extent. To solve this problem, this paper proposes a model for weighting low-rank data based on the method of TRPCA. This model has an additional constraint penalty term that can repair corrupted low-rank data and the effective information in it can be fully utilized. In addition, the norm is used to constrain the sparse tensor to make the sparse effect better. In the experimental part, TRPCA model clusters samples by low-rank tensor. The experimental results on cancer omics data show that our method is superior to other methods.

BACKGROUND: It has been widely accepted that long non-coding RNAs (lncRNAs) play important roles in the development and progression of human diseases. Many association prediction models have been proposed for predicting lncRNA functions and identifying potential lncRNA-disease associations. Nevertheless, among them, little effort has been attempted to measure lncRNA functional similarity, which is an essential part of association prediction models. RESULTS: In this study, we presented an lncRNA functional similarity calculation model, IDSSIM for short, based on an improved disease semantic similarity method, highlight of which is the introduction of information content contribution factor into the semantic value calculation to take into account both the hierarchical structures of disease directed acyclic graphs and the disease specificities. IDSSIM and three state-of-the-art models, i.e., LNCSIM1, LNCSIM2, and ILNCSIM, were evaluated by applying their disease semantic similarity matrices and the lncRNA functional similarity matrices, as well as corresponding matrices of human lncRNA-disease associations coming from either lncRNADisease database or MNDR database, into an association prediction method WKNKN for lncRNA-disease association prediction. In addition, case studies of breast cancer and adenocarcinoma were also performed to validate the effectiveness of IDSSIM. CONCLUSIONS: Results demonstrated that in terms of ROC curves and AUC values, IDSSIM is superior to compared models, and can improve accuracy of disease semantic similarity effectively, leading to increase the association prediction ability of the IDSSIM-WKNKN model; in terms of case studies, most of potential disease-associated lncRNAs predicted by IDSSIM can be confirmed by databases and literatures, implying that IDSSIM can serve as a promising tool for predicting lncRNA functions, identifying potential lncRNA-disease associations, and pre-screening candidate lncRNAs to perform biological experiments. The IDSSIM code, all experimental data and prediction results are available online at https://github.com/CDMB-lab/IDSSIM .

Abstract Background As a machine learning method with high performance and excellent generalization ability, extreme learning machine (ELM) is gaining popularity in various studies. Various ELM-based methods for different fields have been proposed. However, the robustness to noise and outliers is always the main problem affecting the performance of ELM. Results In this paper, an integrated method named correntropy induced loss based sparse robust graph regularized extreme learning machine (CSRGELM) is proposed. The introduction of correntropy induced loss improves the robustness of ELM and weakens the negative effects of noise and outliers. By using the L2,1-norm to constrain the output weight matrix, we tend to obtain a sparse output weight matrix to construct a simpler single hidden layer feedforward neural network model. By introducing the graph regularization to preserve the local structural information of the data, the classification performance of the new method is further improved. Besides, we design an iterative optimization method based on the idea of half quadratic optimization to solve the non-convex problem of CSRGELM. Conclusions The classification results on the benchmark dataset show that CSRGELM can obtain better classification results compared with other methods. More importantly, we also apply the new method to the classification problems of cancer samples and get a good classification effect.

BACKGROUND: MicroRNAs (miRNAs) are non-coding RNAs with regulatory functions. Many studies have shown that miRNAs are closely associated with human diseases. Among the methods to explore the relationship between the miRNA and the disease, traditional methods are time-consuming and the accuracy needs to be improved. In view of the shortcoming of previous models, a method, collaborative matrix factorization based on matrix completion (MCCMF) is proposed to predict the unknown miRNA-disease associations. RESULTS: The complete matrix of the miRNA and the disease is obtained by matrix completion. Moreover, Gaussian Interaction Profile kernel is added to the miRNA functional similarity matrix and the disease semantic similarity matrix. Then the Weight K Nearest Known Neighbors method is used to pretreat the association matrix, so the model is close to the reality. Finally, collaborative matrix factorization method is applied to obtain the prediction results. Therefore, the MCCMF obtains a satisfactory result in the fivefold cross-validation, with an AUC of 0.9569 (0.0005). CONCLUSIONS: The AUC value of MCCMF is higher than other advanced methods in the fivefold cross validation experiment. In order to comprehensively evaluate the performance of MCCMF, accuracy, precision, recall and f-measure are also added. The final experimental results demonstrate that MCCMF outperforms other methods in predicting miRNA-disease associations. In the end, the effectiveness and practicability of MCCMF are further verified by researching three specific diseases.

Epistasis learning, which is aimed at detecting associations between multiple Single Nucleotide Polymorphisms (SNPs) and complex diseases, has gained increasing attention in genome wide association studies. Although much work has been done on mapping the SNPs underlying complex diseases, there is still difficulty in detecting epistatic interactions due to the lack of heuristic information to expedite the search process. In this study, a method EACO is proposed to detect epistatic interactions based on the ant colony optimization (ACO) algorithm, the highlights of which are the introduced heuristic information, fitness function, and a candidate solutions filtration strategy. The heuristic information multi-SURF* is introduced into EACO for identifying epistasis, which is incorporated into ant-decision rules to guide the search with linear time. Two functionally complementary fitness functions, mutual information and the Gini index, are combined to effectively evaluate the associations between SNP combinations and the phenotype. Furthermore, a strategy for candidate solutions filtration is provided to adaptively retain all optimal solutions which yields a more accurate way for epistasis searching. Experiments of EACO, as well as three ACO based methods (AntEpiSeeker, MACOED, and epiACO) and four commonly used methods (BOOST, SNPRuler, TEAM, and epiMODE) are performed on both simulation data sets and a real data set of age-related macular degeneration. Results indicate that EACO is promising in identifying epistasis.

There is much evidence that long non-coding RNA (lncRNA) is associated with many diseases. However, it is time-consuming and expensive to identify meaningful lncRNA-disease associations (LDAs) through medical or biological experiments. Therefore, investigating how to identify more meaningful LDAs is necessary, and at the same time it is conducive to the prevention, diagnosis and treatment of complex diseases. Considering the limitations of some current prediction models, a novel model based on bipartite local model with nearest profile-based association inferring, BLM-NPAI, is developed for predicting LDAs. This model predicts novel LDAs from the lncRNA side and the disease side, respectively. More importantly, for some lncRNAs and diseases without any association, the model can also be predicted by their nearest neighbors. Leave-one-out cross validation (LOOCV) and 5-fold cross validation are implemented for BLM-NPAI to evaluate the performance of this model. Our model is superior to current advanced methods in most cases. In addition, to verify the validity and reliability of BLM-NPAI, three disease cases and three lncRNA cases are analyzed to further evaluate BLM-NPAI. Finally, these predicted novel LDAs are confirmed by using the LncRNA-disease database.

Non-negative Matrix Factorization (NMF) is a dimensionality reduction approach for learning a parts-based and linear representation of non-negative data. It has attracted more attention because of that. In practice, NMF not only neglects the manifold structure of data samples, but also overlooks the priori label information of different classes. In this paper, a novel matrix decomposition method called Hyper-graph regularized Constrained Non-negative Matrix Factorization (HCNMF) is proposed for selecting differentially expressed genes and tumor sample classification. The advantage of hyper-graph learning is to capture local spatial information in high dimensional data. This method incorporates a hyper-graph regularization constraint to consider the higher order data sample relationships. The application of hyper-graph theory can effectively find pathogenic genes in cancer datasets. Besides, the label information is further incorporated in the objective function to improve the discriminative ability of the decomposition matrix. Supervised learning with label information greatly improves the classification effect. We also provide the iterative update rules and convergence proofs for the optimization problems of HCNMF. Experiments under The Cancer Genome Atlas (TCGA) datasets confirm the superiority of HCNMF algorithm compared with other representative algorithms through a set of evaluations.

In recent years, with the diversity and variability of cancer information, the multi-omics data have been applied in various fields. Many existing models of principal component analysis can only process single data, which makes limitations on cancer research. Therefore, in this paper, a new model called integrative principal component analysis (IPCA) is proposed to achieve the unification of multi-omics data. In addition, in order to preserve the high-order manifold structure between the data, an integrative hypergraph regularization principal component analysis (IHPCA) is further proposed by applying the hypergraph regularization constraint. The effectiveness of IHPCA method is tested on four multi-omics datasets. Experimental results show that the proposed method has better performance than other representative methods on sample clustering and common expression genes (co-expression genes) network analysis.

BACKGROUND: Predicting drug-target interactions is time-consuming and expensive. It is important to present the accuracy of the calculation method. There are many algorithms to predict global interactions, some of which use drug-target networks for prediction (ie, a bipartite graph of bound drug pairs and targets known to interact). Although these algorithms can predict some drug-target interactions to some extent, there is little effect for some new drugs or targets that have no known interaction. RESULTS: Since the datasets are usually located at or near low-dimensional nonlinear manifolds, we propose an improved GRMF (graph regularized matrix factorization) method to learn these flow patterns in combination with the previous matrix-decomposition method. In addition, we use one of the pre-processing steps previously proposed to improve the accuracy of the prediction. CONCLUSIONS: Cross-validation is used to evaluate our method, and simulation experiments are used to predict new interactions. In most cases, our method is superior to other methods. Finally, some examples of new drugs and new targets are predicted by performing simulation experiments. And the improved GRMF method can better predict the remaining drug-target interactions.

BACKGROUND: Predicting drug-disease interactions (DDIs) is time-consuming and expensive. Improving the accuracy of prediction results is necessary, and it is crucial to develop a novel computing technology to predict new DDIs. The existing methods mostly use the construction of heterogeneous networks to predict new DDIs. However, the number of known interacting drug-disease pairs is small, so there will be many errors in this heterogeneous network that will interfere with the final results. RESULTS: -norm are introduced in our method to achieve better results than other advanced methods. The network similarities of drugs and diseases with their chemical and semantic similarities are combined in this method. CONCLUSIONS: Cross validation is used to evaluate our method, and simulation experiments are used to predict new interactions using two different datasets. Finally, our prediction accuracy is better than other existing methods. This proves that our method is feasible and effective.

BACKGROUND: Predicting miRNA-disease associations (MDAs) is time-consuming and expensive. It is imminent to improve the accuracy of prediction results. So it is crucial to develop a novel computing technology to predict new MDAs. Although some existing methods can effectively predict novel MDAs, there are still some shortcomings. Especially when the disease matrix is processed, its sparsity is an important factor affecting the final results. RESULTS: -norm are introduced to our method to achieve the highest AUC value than other advanced methods. CONCLUSIONS: 5-fold cross validation is used to evaluate our method, and simulation experiments are used to predict novel associations on Gold Standard Dataset. Finally, our prediction accuracy is better than other existing advanced methods. Therefore, our approach is effective and feasible in predicting novel MDAs.

BACKGROUND: Predicting meaningful miRNA-disease associations (MDAs) is costly. Therefore, an increasing number of researchers are beginning to focus on methods to predict potential MDAs. Thus, prediction methods with improved accuracy are under development. An efficient computational method is proposed to be crucial for predicting novel MDAs. For improved experimental productivity, large biological datasets are used by researchers. Although there are many effective and feasible methods to predict potential MDAs, the possibility remains that these methods are flawed. RESULTS: A simple and effective method, known as Nearest Profile-based Collaborative Matrix Factorization (NPCMF), is proposed to identify novel MDAs. The nearest profile is introduced to our method to achieve the highest AUC value compared with other advanced methods. For some miRNAs and diseases without any association, we use the nearest neighbour information to complete the prediction. CONCLUSIONS: To evaluate the performance of our method, five-fold cross-validation is used to calculate the AUC value. At the same time, three disease cases, gastric neoplasms, rectal neoplasms and colonic neoplasms, are used to predict novel MDAs on a gold-standard dataset. We predict the vast majority of known MDAs and some novel MDAs. Finally, the prediction accuracy of our method is determined to be better than that of other existing methods. Thus, the proposed prediction model can obtain reliable experimental results.

BACKGROUND: Identifying different types of cancer based on gene expression data has become hotspot in bioinformatics research. Clustering cancer gene expression data from multiple cancers to their own class is a significance solution. However, the characteristics of high-dimensional and small samples of gene expression data and the noise of the data make data mining and research difficult. Although there are many effective and feasible methods to deal with this problem, the possibility remains that these methods are flawed. RESULTS: In this paper, we propose the graph regularized low-rank representation under symmetric and sparse constraints (sgLRR) method in which we introduce graph regularization based on manifold learning and symmetric sparse constraints into the traditional low-rank representation (LRR). For the sgLRR method, by means of symmetric constraint and sparse constraint, the effect of raw data noise on low-rank representation is alleviated. Further, sgLRR method preserves the important intrinsic local geometrical structures of the raw data by introducing graph regularization. We apply this method to cluster multi-cancer samples based on gene expression data, which improves the clustering quality. First, the gene expression data are decomposed by sgLRR method. And, a lowest rank representation matrix is obtained, which is symmetric and sparse. Then, an affinity matrix is constructed to perform the multi-cancer sample clustering by using a spectral clustering algorithm, i.e., normalized cuts (Ncuts). Finally, the multi-cancer samples clustering is completed. CONCLUSIONS: A series of comparative experiments demonstrate that the sgLRR method based on low rank representation has a great advantage and remarkable performance in the clustering of multi-cancer samples.

BACKGROUND: Long non-coding RNA (lncRNA) studies play an important role in the development, invasion, and metastasis of the tumor. The analysis and screening of the differential expression of lncRNAs in cancer and corresponding paracancerous tissues provides new clues for finding new cancer diagnostic indicators and improving the treatment. Predicting lncRNA-protein interactions is very important in the analysis of lncRNAs. This article proposes an Ant-Colony-Clustering-Based Bipartite Network (ACCBN) method and predicts lncRNA-protein interactions. The ACCBN method combines ant colony clustering and bipartite network inference to predict lncRNA-protein interactions. RESULTS: A five-fold cross-validation method was used in the experimental test. The results show that the values of the evaluation indicators of ACCBN on the test set are significantly better after comparing the predictive ability of ACCBN with RWR, ProCF, LPIHN, and LPBNI method. CONCLUSIONS: With the continuous development of biology, besides the research on the cellular process, the research on the interaction function between proteins becomes a new key topic of biology. The studies on protein-protein interactions had important implications for bioinformatics, clinical medicine, and pharmacology. However, there are many kinds of proteins, and their functions of interactions are complicated. Moreover, the experimental methods require time to be confirmed because it is difficult to estimate. Therefore, a viable solution is to predict protein-protein interactions efficiently with computers. The ACCBN method has a good effect on the prediction of protein-protein interactions in terms of sensitivity, precision, accuracy, and F1-score.

Tumor samples clustering based on biomolecular data is a hot issue of cancer classifications discovery. How to extract the valuable information from high dimensional genomic data is becoming an urgent problem in tumor samples clustering. In this paper, we introduce manifold regularization into low-rank representation model and present a novel method named Mixed-norm Laplacian regularized Low-Rank Representation (MLLRR) to identify the differentially expressed genes for tumor clustering based on gene expression data. Then, in order to advance the accuracy and stability of tumor clustering, we establish the clustering model based on Penalized Matrix Decomposition (PMD) and propose a novel cluster method named MLLRR-PMD. In this method, the cancer clustering research includes three steps. First, the matrix of gene expression data is decomposed into a low rank representation matrix and a sparse matrix by MLLRR. Second, the differentially expressed genes are identified based on the sparse matrix. Finally, the PMD is applied to cluster the samples based on the differentially expressed genes. The experiment results on simulation data and real genomic data illustrate that MLLRR method enhances the robustness to outliers and achieves remarkable performance in the extraction of differentially expressed genes.

Principal component analysis (PCA) has been used to study the pathogenesis of diseases. To enhance the interpretability of classical PCA, various improved PCA methods have been proposed to date. Among these, a typical method is the so-called sparse PCA, which focuses on seeking sparse loadings. However, the performance of these methods is still far from satisfactory due to their limitation of using unsupervised learning methods; moreover, the class ambiguity within the sample is high. To overcome this problem, this paper developed a new PCA method, which is named the supervised discriminative sparse PCA (SDSPCA). The main innovation of this method is the incorporation of discriminative information and sparsity into the PCA model. Specifically, in contrast to the traditional sparse PCA, which imposes sparsity on the loadings, here, sparse components are obtained to represent the data. Furthermore, via the linear transformation, the sparse components approximate the given label information. On the one hand, sparse components improve interpretability over the traditional PCA, while on the other hand, they are have discriminative abilities suitable for classification purposes. A simple algorithm is developed, and its convergence proof is provided. SDSPCA has been applied to the common-characteristic gene selection and tumor classification on multiview biological data. The sparsity and classification performance of SDSPCA are empirically verified via abundant, reasonable, and effective experiments, and the obtained results demonstrate that SDSPCA outperforms other state-of-the-art methods.

Non-negative Matrix Factorization (NMF), a classical method for dimensionality reduction, has been applied in many fields. It is based on the idea that negative numbers are physically meaningless in various data-processing tasks. Apart from its contribution to conventional data analysis, the recent overwhelming interest in NMF is due to its newly discovered ability to solve challenging data mining and machine learning problems, especially in relation to gene expression data. This survey paper mainly focuses on research examining the application of NMF to identify differentially expressed genes and to cluster samples, and the main NMF models, properties, principles, and algorithms with its various generalizations, extensions, and modifications are summarized. The experimental results demonstrate the performance of the various NMF algorithms in identifying differentially expressed genes and clustering samples.

With the advent of sequencing technology, numerous gene expression data are generated. Identifying differentially expressed genes play an important role in the gene therapy of cancer patients. As an useful mathematical tool, nonnegative matrix factorization (NMF) has been successfully used for identifying differentially expressed genes. In this paper, a novel method named robust graph regularized sparse orthogonal nonnegative matrix factorization (RGSON) is proposed and used for identifying differentially expressed genes, which introduces manifold learning, L1and orthogonal constraints into the objective function. In particular, L2,1-norm minimization is enforced on the objective function to improve the robustness of the algorithm. To prove the validity of the algorithm, experiments on the real genomic dataset are conducted. The results show that RGSON performs more effective than many other methods for identifying differentially expressed genes.

Many real-world problems involve multi-view high-dimension-small-sample-size data analysis, such as multi-omics data. The combination of multi-view databases is supposed to provide a better biological significance. However, the multi-view data always contain noise and outlying entries that result in inaccurate and unreliable. It has become an urgent need how to effectively analyze these data. We proposed a novel convex multi-view low-rank sparse regression (CMLSR) algorithm to do cluster and feature selection. The model was constructed by imposing L2,1-norm and trace norm constraints on the regularization functions. It can diminish the impact of noises and outliers and produce more precise results. Clustering quality was determined by both sparse constraint and low-rank constraint. Finally, we selected characteristic genes based on the projection matrix. The method was used in TCGA multi-view genes expression data sets, annotated according to Gene Ontology (GO). In this paper, we demonstrated the effectiveness of the proposed algorithm through comparing it with the existing methods.

Low-rank representation (LRR) via rank minimization is a high efficiency method for capturing low-dimensional structure embedded in high-dimensional data. However, minimizing the rank of a matrix is NP-hard. In this paper, robust truncated nuclear norm low-rank representation regularized by L2,1-norm method (RTLRR) is proposed. The truncated nuclear norm is introduced to replace the nuclear norm to approximate the rank function. At the same time, L2,1-norm is used to regularize the sparse matrix to achieve better sparse effect of the algorithm. The proposed method is divided into two steps. Firstly, we do singular value decomposition (SVD) to the original data matrix. Then we apply the truncated nuclear norm and L2,1-norm constraints to subproblems and use inexact augmented Lagrange multiplier method to solve subproblems. Finally, the genes with high scores will be identified as differentially expressed genes according to the sparse matrix. The results on The Cancer Genome Atlas (TCGA) data illustrate that the effectiveness of RTLRR method outperforms many methods.

In molecular biology, the selection of feature genes and tumor clustering are the hotspots and difficulties in bioinformatics research. The traditional PCA method based on the minimization of the squares of the loss function is sensitive to the outliers and noise. Therefore, it is necessary to design a new method to weaken the effects of errors and noise. In this paper, we propose a novel PCA method based graph-Laplacian and capped L1-norm, which is called as CgLPCA. The method can preserve the internal geometry of data by introducing graph-Laplacian. In addition, it uses the capped L1-norm on loss function to improve its robustness. The main contribution of this method is to preserve the nonlinear structure of the data while enhancing the robustness of the PCA-based method. We introduce the Augmented Lagrangian multiplier to solve the optimization problem. The CgLPCA method achieves the advanced level in feature selection and tumor clustering among various PCA-based methods.

Non-negative Matrix Factorization (NMF) is widely used as a data dimensionality reduction tool. However, the assumption of most conventional NMF-based methods is that the gene expression data are only destroyed by Gaussian noise. In practice, the gene expression data are unavoidably destroyed by sparse noise. Although Sparsity-Regularized Robust NMF by using L1/2constraint (L1/2-RNMF) can achieve satisfactory results when the sparse noise exists, it does not consider the intrinsic geometric structure in data. Hence, we introduce graph regularization into L1/2-RNMF. In this paper, we developed a novel NMF method named Graph regularized Robust Nonnegative Matrix Factorization (GrRNMF), which mainly consists of two aspects: Firstly, the Gaussian noise and sparse noise are modeled, respectively. Secondly, it can reveal the geometric information in data by adding graph regularization term. Extensive experimental results on The Cancer Genome Atlas (TCGA) data indicate that the GrRNMF method has higher accuracy than other state-of-the-art methods in samples clustering and the selection of differentially expressed genes.

Recent research shows that characteristic gene selection based on gene expression data remains faced with considerable challenges. This is primarily because vast amount of gene expression data have been generated with the development of gene detection technology. Nonetheless, the recognition rate and reliability of gene selection still need to be improved. In this paper, we propose a novel constrained method: robust graph regularized discriminative nonnegative matrix factorization (RGDNMF) for characteristic gene selection. The method mainly includes two aspects: firstly, we incorporate both intrinsic geometrical structure and discriminative label information into the NMF model. Secondly, we adopt L2,1 -norm minimization to both the error function and the regularization term which is robust to noises and outliers in gene data. Furthermore we present the multiplicative update rules and the convergence proof. Our experiments demonstrate that RGDNMF is far more effective than other existing methods.

Principal Component Analysis (PCA) as a tool for dimensionality reduction is widely used in many areas. In the area of bioinformatics, the first principal component of PCA is used to select characteristic genes. In order to improve the robustness of PCA-based method, this paper proposes a novel graph-Laplacian PCA algorithm by adopting L1/2constraint on error function (L1/2gLPCA) for characteristic gene selection. Augmented Lagrange Multipliers (ALM) method is applied to solve the sub-problem. This method gets better results in characteristic gene selection than traditional PCA approach. Meanwhile, the error function based on the L1/2norm helps to reduce the influence of outliers and noise. Extensive experimental results on gene expression data sets demonstrate that our method can get higher identification accuracies than others.

Tumor clustering based on biomolecular data plays a very important role for cancer classifications discovery. To further improve the robustness, stability and accuracy of tumor clustering, we develop a novel dimension reduction method named p-norm singular value decomposition (PSVD) to seek a low-rank approximation matrix to the bimolecular data. To enhance the robustness to outliers, the Lp-norm is taken as the error function and the Schatten p-norm is used as the regularization function in our optimization model. To evaluate the performance of PSVD, Kmeans clustering method is then employed for tumor clustering based on the low-rank approximation matrix. The extensive experiments are performed on gene expression dataset and cancer genome dataset respectively. All experimental results demonstrate that the PSVD-based method outperforms many existing methods. Especially it is experimentally proved that the proposed method is efficient for processing higher dimensional data with good robustness and superior time performance.

Recently, feature extraction and dimensionality reduction have become fundamental tools for many data mining tasks, especially for processing high-dimensional data such as genome data. In this paper, a new feature extraction method based on sparse singular value decomposition (SSVD) is developed. SSVD algorithm is applied to extract differentially expressed genes from two different genome datasets that are all from The Cancer Genome Atlas (TCGA), and then the extracted genes are evaluated by the tools based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. As a gene extraction method, SSVD is also compared with some existing feature extraction methods such as independent component analysis, the p-norm robust feature extraction and sparse principal component analysis. The experimental GO analysis results show that SSVD method outperforms the competitive algorithms. The KEGG analysis results demonstrate the genes which participate in the pathways in cancer. The elaborate experiments prove that SSVD is an effective feature selection method compared with the competitive methods. The KEGG analysis results may provide a meaningful reference to carry out further study for professionals in the field of biomedical science.

Sparse Principal Component Analysis (SPCA) is a method that can get the sparse loadings of the principal components (PCs), and it may formulate PCA as a regression-type optimization problem by using the elastic net. But the selected features are different with each PC and generally independent. A new method named SPCA has been proposed for removing these detect, which replaces the elastic net with L2,1-norm penalty. The results of the method on gene expression data are still unknown. Therefore, we will take a test to prove this point in this paper. Firstly, this method is applied to the simulated data for obtaining an optimal parameter. Secondly, the L2,1SPCA method is applied to the gene expression data, that is the head and neck squamous carcinoma data (HNSC). Thirdly, the characteristic genes are selected according the PCs. The results consist of very lower P-value and very higher hit count, which shows the method of L2,1SPCA can obtain higher recognition accuracy and higher relevancy to the genes. Finally, the experimental results demonstrate that the L2,1SPCA works well and has good performances in the gene expression data.

Robust Principal Component Analysis (RPCA) is an efficient method in the selection of differentially expressed genes. However, nuclear norm minimizes all singular values simultaneously, so it may not be the best solution to replace the low-rank function. In this paper, the truncated nuclear norm is introduced. And a new method named Truncated nuclear norm regularized Robust Principal Component Analysis (TRPCA) is proposed. The method decomposes the observation matrix of genomic data into a low-rank matrix and a sparse matrix. The differentially expressed genes can be selected according to the sparse matrix. The experimental results on the The Cancer Genome Atlas (TCGA) data illustrate that the TRPCA method outperforms other state-of-the-art methods in the selection of differentially expressed genes.

Pathway-based drug discovery overcomes the disadvantages of the “one drug-one target” method, which aims to find the effective drugs to act on single targets. The current method “iPaD” identities the drug-pathway association pairs by taking the lasso-type penalty on the drug-pathway association matrix. In order to enhance the robustness of the methods and be more effective to find the novel drug-pathway association pairs, we introduce a new method named “L2,1-iPaD”. Compared with the iPaD method, we impose the L2,1-norm constraint on the drug-pathway association coefficient matrix. By applying our method to a real widely datasets (CCLE dataset), we demonstrate that our method is superior to the iPaD method. And our method can obtain the smaller P-values than the iPaD method by performing permutation test to assess the significance of the identified drug-pathway association pairs. More importantly, compared with the iPaD method, our method can identify larger numbers of validated drug-pathway association pairs. The experimental results on the real dataset demonstrate the effectiveness of our method.

BACKGROUND: Detecting and visualizing nonlinear interaction effects of single nucleotide polymorphisms (SNPs) or epistatic interactions are important topics in bioinformatics since they play an important role in unraveling the mystery of "missing heritability". However, related studies are almost limited to pairwise epistatic interactions due to their methodological and computational challenges. RESULTS: We develop CINOEDV (Co-Information based N-Order Epistasis Detector and Visualizer) for the detection and visualization of epistatic interactions of their orders from 1 to n (n ≥ 2). CINOEDV is composed of two stages, namely, detecting stage and visualizing stage. In detecting stage, co-information based measures are employed to quantify association effects of n-order SNP combinations to the phenotype, and two types of search strategies are introduced to identify n-order epistatic interactions: an exhaustive search and a particle swarm optimization based search. In visualizing stage, all detected n-order epistatic interactions are used to construct a hypergraph, where a real vertex represents the main effect of a SNP and a virtual vertex denotes the interaction effect of an n-order epistatic interaction. By deeply analyzing the constructed hypergraph, some hidden clues for better understanding the underlying genetic architecture of complex diseases could be revealed. CONCLUSIONS: Experiments of CINOEDV and its comparison with existing state-of-the-art methods are performed on both simulation data sets and a real data set of age-related macular degeneration. Results demonstrate that CINOEDV is promising in detecting and visualizing n-order epistatic interactions. CINOEDV is implemented in R and is freely available from R CRAN: http://cran.r-project.org and https://sourceforge.net/projects/cinoedv/files/ .

With the development of deep sequencing technologies, many RNA-Seq data have been generated. Researchers have proposed many methods based on the sparse theory to identify the differentially expressed genes from these data. In order to improve the performance of sparse principal component analysis, in this paper, we propose a novel class-information-based sparse component analysis (CISCA) method which introduces the class information via a total scatter matrix. First, CISCA normalizes the RNA-Seq data by using a Poisson model to obtain their differential sections. Second, the total scatter matrix is gotten by combining the between-class and within-class scatter matrices. Third, we decompose the total scatter matrix by using singular value decomposition and construct a new data matrix by using singular values and left singular vectors. Then, aiming at obtaining sparse components, CISCA decomposes the constructed data matrix by solving an optimization problem with sparse constraints on loading vectors. Finally, the differentially expressed genes are identified by using the sparse loading vectors. The results on simulation and real RNA-Seq data demonstrate that our method is effective and suitable for analyzing these data.

Many methods have been considered for gene selection and analysis of gene expression data. Nonetheless, there still exists the considerable space for improving the explicitness and reliability of gene selection. To this end, this paper proposes a novel method named robust graph regularized non-negative matrix factorization for characteristic gene selection using gene expression data, which mainly contains two aspects: Firstly, enforcing L21-norm minimization on error function which is robust to outliers and noises in data points. Secondly, it considers that the samples lie in low-dimensional manifold which embeds in a high-dimensional ambient space, and reveals the data geometric structure embedded in the original data. To demonstrate the validity of the proposed method, we apply it to gene expression data sets involving various human normal and tumor tissue samples and the results demonstrate that the method is effective and feasible.

Microarray techniques have been used to delineate cancer groups or to identify candidate genes for cancer prognosis. As such problems can be viewed as classification ones, various classification methods have been applied to analyze or interpret gene expression data. In this paper, we propose a novel method based on robust principal component analysis (RPCA) to classify tumor samples of gene expression data. Firstly, RPCA is utilized to highlight the characteristic genes associated with a special biological process. Then, RPCA and RPCA+LDA (robust principal component analysis and linear discriminant analysis) are used to identify the features. Finally, support vector machine (SVM) is applied to classify the tumor samples of gene expression data based on the identified features. Experiments on seven data sets demonstrate that our methods are effective and feasible for tumor classification.

How to identify a set of genes that are relevant to a key biological process is an important issue in current molecular biology. In this paper, we propose a novel method to discover differentially expressed genes based on robust principal component analysis (RPCA). In our method, we treat the differentially and non-differentially expressed genes as perturbation signals S and low-rank matrix A, respectively. Perturbation signals S can be recovered from the gene expression data by using RPCA. To discover the differentially expressed genes associated with special biological progresses or functions, the scheme is given as follows. Firstly, the matrix D of expression data is decomposed into two adding matrices A and S by using RPCA. Secondly, the differentially expressed genes are identified based on matrix S. Finally, the differentially expressed genes are evaluated by the tools based on Gene Ontology. A larger number of experiments on hypothetical and real gene expression data are also provided and the experimental results show that our method is efficient and effective.