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Clinical trials indicate that the dysregulation of microRNAs (miRNAs) is closely associated with the development of diseases. Therefore, predicting miRNA-disease associations is significant for studying the pathogenesis of diseases. Since traditional wet-lab methods are resource-intensive, cost-saving computational models can be an effective complementary tool in biological experiments. In this work, a locality-constrained linear coding is proposed to predict associations (ILLCEL). Among them, ILLCEL adopts miRNA sequence similarity, miRNA functional similarity, disease semantic similarity, and interaction profile similarity obtained by locality-constrained linear coding (LLC) as the priori information. Next, features and similarities extracted from multiperspectives are input to the ensemble learning framework to improve the comprehensiveness of the prediction. Significantly, the introduction of hypergraph-regular terms improves the accuracy of prediction by describing complex associations between samples. The results under fivefold cross validation indicate that ILLCEL achieves superior prediction performance. In case studies, known associations are accurately predicted and novel associations are verified in HMDD v3.2, miRCancer, and existing literature. It is concluded that ILLCEL can be served as a powerful tool for inferring potential associations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tensor Robust Principal Component Analysis (TRPCA) has achieved promising results in the analysis of genomics data. However, the TRPCA model under the existing tensor singular value decomposition (t -SVD) framework insufficiently extracts the potential low-rank structure of the data, resulting in suboptimal restored components. Simultaneously, the tensor nuclear norm (TNN) defined based on t -SVD uses the same standard to handle various singular values. TNN ignores the difference of singular values, leading to the failure of the main information that needs to be well preserved. To preserve the heterogeneous structure in the low-rank information, we propose a novel TNN and extend it to the TRPCA model. Potential low-rank space may contain important information. We learn the low-rank structural information from the core tensor. The singular value space contains the association information between genes and cancers. The p -shrinkage generalized threshold function is utilized to preserve the low-rank properties of larger singular values. The optimization problem is solved by the alternating direction method of the multiplier (ADMM) algorithm. Clustering and feature selection experiments are performed on the TCGA data set. The experimental results show that the proposed model is more promising than other state-of-the-art tensor decomposition methods. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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 $L_{2,1}$ 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. [ABSTRACT FROM AUTHOR]

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 L2,1-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Non-negative Matrix Factorization (NMF) is a popular data dimension reduction method in recent years. The traditional NMF method has high sensitivity to data noise. In the paper, we propose a model called Sparse Robust Graph-regularized Non-negative Matrix Factorization based on Correntropy (SGNMFC). The maximized correntropy replaces the traditional minimized Euclidean distance to improve the robustness of the algorithm. Through the kernel function, correntropy can give less weight to outliers and noise in data but give greater weight to meaningful data. Meanwhile, the geometry structure of the high-dimensional data is completely preserved in the low-dimensional manifold through the graph regularization. Feature selection and sample clustering are commonly used methods for analyzing genes. Sparse constraints are applied to the loss function to reduce matrix complexity and analysis difficulty. Comparing the other five similar methods, the effectiveness of the SGNMFC model is proved by selection of differentially expressed genes and sample clustering experiments in three The Cancer Genome Atlas (TCGA) datasets. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nonnegative Matrix Factorization (NMF) is a significant big data analysis technique. However, standard NMF regularized by simple graph does not have discriminative function, and traditional graph models cannot accurately reflect the problem of multigeometry information between data. To solve the above problem, this paper proposed a new method called Hypergraph Regularized Discriminative Nonnegative Matrix Factorization (HDNMF), which captures intrinsic geometry by constructing hypergraphs rather than simple graphs. The introduction of the hypergraph method allows high-order relationships between samples to be considered, and the introduction of label information enables the method to have discriminative effect. Both the hypergraph Laplace and the discriminative label information are utilized together to learn the projection matrix in the standard method. In addition, we offered a corresponding multiplication update solution for the optimization. Experiments indicate that the method proposed is more effective by comparing with the earlier methods. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the big data era, sequencing technology has produced a large number of biological sequencing data. Different views of the cancer genome data provide sufficient complementary information to explore genetic activity. The identification of differentially expressed genes from multiview cancer gene data is of great importance in cancer diagnosis and treatment. In this paper, we propose a novel method for identifying differentially expressed genes based on tensor robust principal component analysis (TRPCA), which extends the matrix method to the processing of multiway data. To identify differentially expressed genes, the plan is carried out as follows. First, multiview data containing cancer gene expression data from different sources are prepared. Second, the original tensor is decomposed into a sum of a low-rank tensor and a sparse tensor using TRPCA. Third, the differentially expressed genes are considered to be sparse perturbed signals and then identified based on the sparse tensor. Fourth, the differentially expressed genes are evaluated using Gene Ontology and Gene Cards tools. The validity of the TRPCA method was tested using two sets of multiview data. The experimental results showed that our method is superior to the representative methods in efficiency and accuracy aspects. [ABSTRACT FROM AUTHOR]

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: A novel method, known as the dual-network L2,1-collaborative matrix factorization, is proposed to predict novel DDIs. The Gaussian interaction profile kernels and L2,1-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Identifying differentially expressed genes from the thousands of genes is a challenging task. Robust principal component analysis (RPCA) is an efficient method in the identification of differentially expressed genes. RPCA method uses nuclear norm to approximate the rank function. However, theoretical studies showed that the nuclear norm minimizes all singular values, so it may not be the best solution to approximate the rank function. The truncated nuclear norm is defined as the sum of some smaller singular values, which may achieve a better approximation of the rank function than nuclear norm. In this paper, a novel method is proposed by replacing nuclear norm of RPCA with the truncated nuclear norm, which is named robust principal component analysis regularized by truncated nuclear norm (TRPCA). The method decomposes the observation matrix of genomic data into a low-rank matrix and a sparse matrix. Because the significant genes can be considered as sparse signals, the differentially expressed genes are viewed as the sparse perturbation signals. Thus, the differentially expressed genes can be identified according to the sparse matrix. The experimental results on The Cancer Genome Atlas data illustrate that the TRPCA method outperforms other state-of-the-art methods in the identification of differentially expressed genes. [ABSTRACT FROM PUBLISHER]

In modern molecular biology, the hotspots and difficulties of this field are identifying characteristic genes from gene expression data. Traditional reconstruction-error-minimization model principal component analysis (PCA) as a matrix decomposition method uses quadratic error function, which is known sensitive to outliers and noise. Hence, it is necessary to learn a good PCA method when outliers and noise exist. In this paper, we develop a novel PCA method enforcing P-norm on error function and graph-Laplacian regularization term for matrix decomposition problem, which is called as PgLPCA. The heart of the method designing for reducing outliers and noise is a new error function based on non-convex proximal P-norm. Besides, Laplacian regularization term is used to find the internal geometric structure in the data representation. To solve the minimization problem, we develop an efficient optimization algorithm based on the augmented Lagrange multiplier method. This method is used to select characteristic genes and cluster the samples from explosive biological data, which has higher accuracy than compared methods. [ABSTRACT FROM PUBLISHER]

Principal Component Analysis (PCA) as a tool for dimensionality reduction is widely used in many areas. In the area of bioinformatics, each involved variable corresponds to a specific gene. In order to improve the robustness of PCA-based method, this paper proposes a novel graph-Laplacian PCA algorithm by adopting L1/2 constraint (L1/2 gLPCA) on error function for feature (gene) extraction. The error function based on L1/2-norm helps to reduce the influence of outliers and noise. Augmented Lagrange Multipliers (ALM) method is applied to solve the subproblem. This method gets better results in feature extraction than other state-of-the-art PCA-based methods. Extensive experimental results on simulation data and gene expression data sets demonstrate that our method can get higher identification accuracies than others. [ABSTRACT FROM AUTHOR]

The Cancer Genome Atlas (TCGA) dataset provides us more opportunities to systematically and comprehensively learn some biological mechanism of cancers formation, growth and metastasis. Since TCGA dataset includes heterogeneous data, it is one of the bioinformatics bottlenecks to mine some meaningful information from them. In this paper, to improve the performance of Robust Principal Component Analysis (RPCA) analyzing these heterogeneous data, a modified RPCA-based method, Block-Constraint Robust Principal Component Analysis (BCRPCA), is proposed. Since different categories data have different peculiarities, BCRPCA enforces different constraint intensities on different categories to improve the performance of RPCA. Firstly, the observation matrix of TCGA data is decomposed into two adding matrices A and S by using BCRPCA. Secondly, we use a ranking scheme to evaluate every feature and project these features to the genes. Then, the genes with high scores will be identified as differentially expressed ones. The main contributions of this paper are as following: firstly, it proposes, for the first time, the idea and method of BCRPCA to model TCGA data; secondly, it provides a BCRPCA-based framework for integrated analysis of TCGA data. The results show that our method is effective and suitable to analyze these data. [ABSTRACT FROM PUBLISHER]

Recent research has demonstrated that characteristic gene selection based on gene expression data remains faced with considerable challenges. This is primarily because gene expression data are typically high dimensional, negative, non-sparse and noisy. However, existing methods for data analysis are able to cope with only some of these challenges. In this paper, we address all of these challenges with a unified method: nonnegative matrix factorization via the L2,1-norm (NMF-L2,1). While L2,1-norm minimization is applied to both the error function and the regularization term, our method is robust to outliers and noise in the data and generates sparse results. The application of our method to plant and tumor gene expression data demonstrates that NMF-L2,1 can extract more characteristic genes than other existing state-of-the-art methods. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]