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Circular RNAs (circRNAs) play vital roles in transcription and translation. Identification of circRNA-RBP (RNA-binding protein) interaction sites has become a fundamental step in molecular and cell biology. Deep learning (DL)-based methods have been proposed to predict circRNA-RBP interaction sites and achieved impressive identification performance. However, those methods cannot effectively capture long-distance dependencies, and cannot effectively utilize the interaction information of multiple features. To overcome those limitations, we propose a DL-based model iCRBP-LKHA using deep hybrid networks for identifying circRNA-RBP interaction sites. iCRBP-LKHA adopts five encoding schemes. Meanwhile, the neural network architecture, which consists of large kernel convolutional neural network (LKCNN), convolutional block attention module with one-dimensional convolution (CBAM-1D) and bidirectional gating recurrent unit (BiGRU), can explore local information, global context information and multiple features interaction information automatically. To verify the effectiveness of iCRBP-LKHA, we compared its performance with shallow learning algorithms on 37 circRNAs datasets and 37 circRNAs stringent datasets. And we compared its performance with state-of-the-art DL-based methods on 37 circRNAs datasets, 37 circRNAs stringent datasets and 31 linear RNAs datasets. The experimental results not only show that iCRBP-LKHA outperforms other competing methods, but also demonstrate the potential of this model in identifying other RNA-RBP interaction sites.

Abstract Enhancers are small regions of DNA that bind to proteins, which enhance the transcription of genes. The enhancer may be located upstream or downstream of the gene. It is not necessarily close to the gene to be acted on, because the entanglement structure of chromatin allows the positions far apart in the sequence to have the opportunity to contact each other. Therefore, identifying enhancers and their strength is a complex and challenging task. In this article, a new prediction method based on deep learning is proposed to identify enhancers and enhancer strength, called iEnhancer-DCLA. Firstly, we use word2vec to convert k-mers into number vectors to construct an input matrix. Secondly, we use convolutional neural network and bidirectional long short-term memory network to extract sequence features, and finally use the attention mechanism to extract relatively important features. In the task of predicting enhancers and their strengths, this method has improved to a certain extent in most evaluation indexes. In summary, we believe that this method provides new ideas in the analysis of enhancers.

Abstract 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.

Accumulating evidence suggests that circRNAs play crucial roles in human diseases. CircRNA-disease association prediction is extremely helpful in understanding pathogenesis, diagnosis, and prevention, as well as identifying relevant biomarkers. During the past few years, a large number of deep learning (DL) based methods have been proposed for predicting circRNA-disease association and achieved impressive prediction performance. However, there are two main drawbacks to these methods. The first is these methods underutilize biometric information in the data. Second, the features extracted by these methods are not outstanding to represent association characteristics between circRNAs and diseases. In this study, we developed a novel deep learning model, named iCircDA-NEAE, to predict circRNA-disease associations. In particular, we use disease semantic similarity, Gaussian interaction profile kernel, circRNA expression profile similarity, and Jaccard similarity simultaneously for the first time, and extract hidden features based on accelerated attribute network embedding (AANE) and dynamic convolutional autoencoder (DCAE). Experimental results on the circR2Disease dataset show that iCircDA-NEAE outperforms other competing methods significantly. Besides, 16 of the top 20 circRNA-disease pairs with the highest prediction scores were validated by relevant literature. Furthermore, we observe that iCircDA-NEAE can effectively predict new potential circRNA-disease associations. Author summary CircRNA-disease association prediction is extremely helpful in understanding pathogenesis, diagnosis, and prevention, as well as identifying relevant biomarkers. In this paper, we proposed a novel deep learning-based method called iCircDA-NEAE to discover new potential circRNA-disease associations. Experimental results demonstrated that iCircDA-NEAE outperforms other state-of-the-art prediction methods, and can accurately predict potential circRNA-disease associations. Furthermore, according to the relevant literature, we observed that novel circRNA-disease associations predicted by iCircDA-NEAE are potential associations. The performance of iCircDA-NEAE mainly depends on three factors: (i) iCircDA-NEAE incorporates multi-source biometric information to measure complex associations between circRNAs and diseases. (ii) iCircDA-NEAE uses disease semantic similarity, Gaussian interaction kernel (GIP), circRNA expression profile similarity, and Jaccard similarity to make the most of biometric information in the data. (iii) iCircDA-NEAE incorporates the advantages of ANNE and DCAE, which not only effectively integrates multi-source information, but also effectively captures hidden high-level information of data.

Abstract Background As one of the deadliest diseases in the world, cancer is driven by a few somatic mutations that disrupt the normal growth of cells, and leads to abnormal proliferation and tumor development. The vast majority of somatic mutations did not affect the occurrence and development of cancer; thus, identifying the mutations responsible for tumor occurrence and development is one of the main targets of current cancer treatments. Results To effectively identify driver genes, we adopted a semi-local centrality measure and gene mutation effect function to assess the effect of gene mutations on changes in gene expression patterns. Firstly, we calculated the mutation score for each gene. Secondly, we identified differentially expressed genes (DEGs) in the cohort by comparing the expression profiles of tumor samples and normal samples, and then constructed a local network for each mutation gene using DEGs and mutant genes according to the protein–protein interaction network. Finally, we calculated the score of each mutant gene according to the objective function. The top-ranking mutant genes were selected as driver genes. We name the proposed method as mutations effect and network centrality. Conclusions Four types of cancer data in The Cancer Genome Atlas were tested. The experimental data proved that our method was superior to the existing network-centric method, as it was able to quickly and easily identify driver genes and rare driver factors.

Abstract Background Circular RNAs (circRNAs) are a class of single-stranded RNA molecules with a closed-loop structure. A growing body of research has shown that circRNAs are closely related to the development of diseases. Because biological experiments to verify circRNA-disease associations are time-consuming and wasteful of resources, it is necessary to propose a reliable computational method to predict the potential candidate circRNA-disease associations for biological experiments to make them more efficient. Results In this paper, we propose a double matrix completion method (DMCCDA) for predicting potential circRNA-disease associations. First, we constructed a similarity matrix of circRNA and disease according to circRNA sequence information and semantic disease information. We also built a Gauss interaction profile similarity matrix for circRNA and disease based on experimentally verified circRNA-disease associations. Then, the corresponding circRNA sequence similarity and semantic similarity of disease are used to update the association matrix from the perspective of circRNA and disease, respectively, by matrix multiplication. Finally, from the perspective of circRNA and disease, matrix completion is used to update the matrix block, which is formed by splicing the association matrix obtained in the previous step with the corresponding Gaussian similarity matrix. Compared with other approaches, the model of DMCCDA has a relatively good result in leave-one-out cross-validation and five-fold cross-validation. Additionally, the results of the case studies illustrate the effectiveness of the DMCCDA model. Conclusion The results show that our method works well for recommending the potential circRNAs for a disease for biological experiments.

Abstract Background MicroRNAs (miRNAs) have been confirmed to have close relationship with various human complex diseases. The identification of disease-related miRNAs provides great insights into the underlying pathogenesis of diseases. However, it is still a big challenge to identify which miRNAs are related to diseases. As experimental methods are in general expensive and time‐consuming, it is important to develop efficient computational models to discover potential miRNA-disease associations. Methods This study presents a novel prediction method called HFHLMDA, which is based on high-dimensionality features and hypergraph learning, to reveal the association between diseases and miRNAs. Firstly, the miRNA functional similarity and the disease semantic similarity are integrated to form an informative high-dimensionality feature vector. Then, a hypergraph is constructed by the K-Nearest-Neighbor (KNN) method, in which each miRNA-disease pair and its k most relevant neighbors are linked as one hyperedge to represent the complex relationships among miRNA-disease pairs. Finally, the hypergraph learning model is designed to learn the projection matrix which is used to calculate uncertain miRNA-disease association score. Result Compared with four state-of-the-art computational models, HFHLMDA achieved best results of 92.09% and 91.87% in leave-one-out cross validation and fivefold cross validation, respectively. Moreover, in case studies on Esophageal neoplasms, Hepatocellular Carcinoma, Breast Neoplasms, 90%, 98%, and 96% of the top 50 predictions have been manually confirmed by previous experimental studies. Conclusion MiRNAs have complex connections with many human diseases. In this study, we proposed a novel computational model to predict the underlying miRNA-disease associations. All results show that the proposed method is effective for miRNA–disease association predication.

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 L 2,1-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.

microRNAs (miRNAs) are small non-coding RNAs related to a number of complicated biological processes. A growing body of studies have suggested that miRNAs are closely associated with many human diseases. It is meaningful to consider disease-related miRNAs as potential biomarkers, which could greatly contribute to understanding the mechanisms of complex diseases and benefit the prevention, detection, diagnosis and treatment of extraordinary diseases. In this study, we presented a novel model named Graph Convolutional Autoencoder for miRNA-Disease Association Prediction (GCAEMDA). In the proposed model, we utilized miRNA-miRNA similarities, disease-disease similarities and verified miRNA-disease associations to construct a heterogeneous network, which is applied to learn the embeddings of miRNAs and diseases. In addition, we separately constructed miRNA-based and disease-based sub-networks. Combining the embeddings of miRNAs and diseases, graph convolutional autoencoder (GCAE) was utilized to calculate association scores of miRNA-disease on two sub-networks, respectively. Furthermore, we obtained final prediction scores between miRNAs and diseases by adopting an average ensemble way to integrate the prediction scores from two types of subnetworks. To indicate the accuracy of GCAEMDA, we applied different cross validation methods to evaluate our model whose performances were better than the state-of-the-art models. Case studies on a common human diseases were also implemented to prove the effectiveness of GCAEMDA. The results demonstrated that GCAEMDA was beneficial to infer potential associations of miRNA-disease.

An increasing number of experiments had verified that miRNA expression is related to human diseases. The miRNA expression profile may be an indicator of clinical diagnosis and provides a new direction for the prevention and treatment of complex diseases. In this work, we present a weighted voting-based model for predicting miRNA–disease association (WVMDA). To reasonably build a network of similarity, we established credibility similarity based on the reliability of known associations and used it to improve the original incomplete similarity. To eliminate noise interference as much as possible while maintaining more reliable similarity information, we developed a filter. More importantly, to ensure the fairness and efficiency of weighted voting, we focus on the design of weighting. Finally, cross-validation experiments and case studies are undertaken to verify the efficacy of the proposed model. The results showed that WVMDA could efficiently identify miRNAs associated with the disease.

MicroRNAs (miRNAs) are small non-coding RNAs that have been demonstrated to be related to numerous complex human diseases. Considerable studies have suggested that miRNAs affect many complicated bioprocesses. Hence, the investigation of disease-related miRNAs by utilizing computational methods is warranted. In this study, we presented an improved label propagation for miRNA–disease association prediction (ILPMDA) method to observe disease-related miRNAs. First, we utilized similarity kernel fusion to integrate different types of biological information for generating miRNA and disease similarity networks. Second, we applied the weighted k-nearest known neighbor algorithm to update verified miRNA–disease association data. Third, we utilized improved label propagation in disease and miRNA similarity networks to make association prediction. Furthermore, we obtained final prediction scores by adopting an average ensemble method to integrate the two kinds of prediction results. To evaluate the prediction performance of ILPMDA, two types of cross-validation methods and case studies on three significant human diseases were implemented to determine the accuracy and effectiveness of ILPMDA. All results demonstrated that ILPMDA had the ability to discover potential miRNA–disease associations.

Abstract Background The aberrant expression of microRNAs is closely connected to the occurrence and development of a great deal of human diseases. To study human diseases, numerous effective computational models that are valuable and meaningful have been presented by researchers. Results Here, we present a computational framework based on graph Laplacian regularized L 2, 1 -nonnegative matrix factorization (GRL 2, 1 -NMF) for inferring possible human disease-connected miRNAs. First, manually validated disease-connected microRNAs were integrated, and microRNA functional similarity information along with two kinds of disease semantic similarities were calculated. Next, we measured Gaussian interaction profile (GIP) kernel similarities for both diseases and microRNAs. Then, we adopted a preprocessing step, namely, weighted K nearest known neighbours (WKNKN), to decrease the sparsity of the miRNA-disease association matrix network. Finally, the GRL 2,1 -NMF framework was used to predict links between microRNAs and diseases. Conclusions The new method (GRL2, 1-NMF) achieved AUC values of 0.9280 and 0.9276 in global leave-one-out cross validation (global LOOCV) and five-fold cross validation (5-CV), respectively, showing that GRL2, 1-NMF can powerfully discover potential disease-related miRNAs, even if there is no known associated disease.

Abstract Background Although there are huge volumes of genomic data, how to decipher them and identify driver events is still a challenge. The current methods based on network typically use the relationship between genomic events and consequent changes in gene expression to nominate putative driver genes. But there may exist some relationships within the transcriptional network. Methods We developed MECoRank, a novel method that improves the recognition accuracy of driver genes. MECoRank is based on bipartite graph to propagates the scores via an iterative process. After iteration, we will obtain a ranked gene list for each patient sample. Then, we applied the Condorcet voting method to determine the most impactful drivers in a population. Results We applied MECoRank to three cancer datasets to reveal candidate driver genes which have a greater impact on gene expression. Experimental results show that our method not only can identify more driver genes that have been validated than other methods, but also can recognize some impactful novel genes which have been proved to be more important in literature. Conclusions We propose a novel approach named MECoRank to prioritize driver genes based on their impact on the expression in the molecular interaction network. This method not only assesses mutation’s effect on the transcriptional network, but also assesses the differential expression’s effect within the transcriptional network. And the results demonstrated that MECoRank has better performance than the other competing approaches in identifying driver genes.

Abstract 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 A robust collaborative matrix factorization (RCMF) is proposed to predict novel MDAs. The L2,1-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.

Abstract 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.

miRNAs belong to small non-coding RNAs that are related to a number of complicated biological processes. Considerable studies have suggested that miRNAs are closely associated with many human diseases. In this study, we proposed a computational model based on Similarity Constrained Matrix Factorization for miRNA-Disease Association Prediction (SCMFMDA). In order to effectively combine different disease and miRNA similarity data, we applied similarity network fusion algorithm to obtain integrated disease similarity (composed of disease functional similarity, disease semantic similarity and disease Gaussian interaction profile kernel similarity) and integrated miRNA similarity (composed of miRNA functional similarity, miRNA sequence similarity and miRNA Gaussian interaction profile kernel similarity). In addition, the L2 regularization terms and similarity constraint terms were added to traditional Nonnegative Matrix Factorization algorithm to predict disease-related miRNAs. SCMFMDA achieved AUCs of 0.9675 and 0.9447 based on global Leave-one-out cross validation and five-fold cross validation, respectively. Furthermore, the case studies on two common human diseases were also implemented to demonstrate the prediction accuracy of SCMFMDA. The out of top 50 predicted miRNAs confirmed by experimental reports that indicated SCMFMDA was effective for prediction of relationship between miRNAs and diseases.

MicroRNAs (miRNAs) that belong to non-coding RNAs are verified to be closely associated with several complicated biological processes and human diseases. In this study, we proposed a novel model that was Similarity Network Fusion and Inductive Matrix Completion for miRNA-Disease Association Prediction (SNFIMCMDA). We applied inductive matrix completion (IMC) method to acquire possible associations between miRNAs and diseases, which also could obtain corresponding correlation scores. IMC was performed based on the verified connections of miRNA–disease, miRNA similarity, and disease similarity. In addition, miRNA similarity and disease similarity were calculated by similarity network fusion, which could masterly integrate multiple data types to obtain target data. We integrated miRNA functional similarity and Gaussian interaction profile kernel similarity by similarity network fusion to obtain miRNA similarity. Similarly, disease similarity was integrated in this way. To indicate the utility and effectiveness of SNFIMCMDA, we both applied global leave-one-out cross-validation and five-fold cross-validation to validate our model. Furthermore, case studies on three significant human diseases were also implemented to prove the effectiveness of SNFIMCMDA. The results demonstrated that SNFIMCMDA was effective for prediction of possible associations of miRNA–disease.

The dimensionality reduction method accompanied by different norm constraints plays an important role in mining useful information from large-scale gene expression data. In this article, a novel method named Lp-norm and L2,1-norm constrained graph Laplacian principal component analysis (PL21GPCA) based on traditional principal component analysis (PCA) is proposed for robust tumor sample clustering and gene network module discovery. Three aspects are highlighted in the PL21GPCA method. First, to degrade the high sensitivity to outliers and noise, the non-convex proximal Lp-norm (0 < p < 1)constraint is applied on the loss function. Second, to enhance the sparsity of gene expression in cancer samples, the L2,1-norm constraint is used on one of the regularization terms. Third, to retain the geometric structure of the data, we introduce the graph Laplacian regularization item to the PL21GPCA optimization model. Extensive experiments on five gene expression datasets, including one benchmark dataset, two single-cancer datasets from The Cancer Genome Atlas (TCGA), and two integrated datasets of multiple cancers from TCGA, are performed to validate the effectiveness of our method. The experimental results demonstrate that the PL21GPCA method performs better than many other methods in terms of tumor sample clustering. Additionally, this method is used to discover the gene network modules for the purpose of finding key genes that may be associated with some cancers.

Abstract Background Although synonymous single nucleotide variants (sSNVs) do not alter the protein sequences, they have been shown to play an important role in human disease. Distinguishing pathogenic sSNVs from neutral ones is challenging because pathogenic sSNVs tend to have low prevalence. Although many methods have been developed for predicting the functional impact of single nucleotide variants, only a few have been specifically designed for identifying pathogenic sSNVs. Results In this work, we describe a computational model, IDSV (Identification of Deleterious Synonymous Variants), which uses random forest (RF) to detect deleterious sSNVs in human genomes. We systematically investigate a total of 74 multifaceted features across seven categories: splicing, conservation, codon usage, sequence, pre-mRNA folding energy, translation efficiency, and function regions annotation features. Then, to remove redundant and irrelevant features and improve the prediction performance, feature selection is employed using the sequential backward selection method. Based on the optimized 10 features, a RF classifier is developed to identify deleterious sSNVs. The results on benchmark datasets show that IDSV outperforms other state-of-the-art methods in identifying sSNVs that are pathogenic. Conclusions We have developed an efficient feature-based prediction approach (IDSV) for deleterious sSNVs by using a wide variety of features. Among all the features, a compact and useful feature subset that has an important implication for identifying deleterious sSNVs is identified. Our results indicate that besides splicing and conservation features, a new translation efficiency feature is also an informative feature for identifying deleterious sSNVs. While the function regions annotation and sequence features are weakly informative, they may have the ability to discriminate deleterious sSNVs from benign ones when combined with other features. The data and source code are available on website http://bioinfo.ahu.edu.cn:8080/IDSV.

Identifying driver genes that contribute to cancer progression from numerous passenger genes, although a central goal, is a major challenge. The protein–protein interaction network provides convenient and reasonable assistance for driver gene discovery. Random walk–based methods have been widely used to prioritize nodes in social or biological networks. However, most studies select the next arriving node uniformly from the random walker's neighbors. Few consider transiting preference according to the degree of random walker's neighbors. In this study, based on the random walk method, we propose a novel approach named Driver_IRW (Driver genes discovery with Improved Random Walk method), to prioritize cancer genes in cancer-related network. The key idea of Driver_IRW is to assign different transition probabilities for different edges of a constructed cancer-related network in accordance with the degree of the nodes' neighbors. Furthermore, the global centrality (here is betweenness centrality) and Katz feedback centrality are incorporated into the framework to evaluate the probability to walk to the seed nodes. Experimental results on four cancer types indicate that Driver_IRW performs more efficiently than some previously published methods for uncovering known cancer-related genes. In conclusion, our method can aid in prioritizing cancer-related genes and complement traditional frequency and network-based methods.

Abstract Background Identifying epistasis or epistatic interactions, which refer to nonlinear interaction effects of single nucleotide polymorphisms (SNPs), is essential to understand disease susceptibility and to detect genetic architectures underlying complex diseases. Though many works have been done for identifying epistatic interactions, due to their methodological and computational challenges, the algorithmic development is still ongoing. Results In this study, a method epiACO is proposed to identify epistatic interactions, which based on ant colony optimization algorithm. Highlights of epiACO are the introduced fitness function Svalue, path selection strategies, and a memory based strategy. The Svalue leverages the advantages of both mutual information and Bayesian network to effectively and efficiently measure associations between SNP combinations and the phenotype. Two path selection strategies, i.e., probabilistic path selection strategy and stochastic path selection strategy, are provided to adaptively guide ant behaviors of exploration and exploitation. The memory based strategy is designed to retain candidate solutions found in the previous iterations, and compare them to solutions of the current iteration to generate new candidate solutions, yielding a more accurate way for identifying epistasis. Conclusions Experiments of epiACO and its comparison with other recent methods epiMODE, TEAM, BOOST, SNPRuler, AntEpiSeeker, AntMiner, MACOED, and IACO are performed on both simulation data sets and a real data set of age-related macular degeneration. Results show that epiACO is promising in identifying epistasis and might be an alternative to existing methods.

Low-Rank Representation (LRR) is a powerful subspace clustering method because of its successful learning of low-dimensional subspace of data. With the breakthrough of “OMics” technology, many LRR-based methods have been proposed and used to cancer clustering based on gene expression data. Moreover, studies have shown that besides gene expression data, some other genomic data in TCGA also contain important information for cancer research. Therefore, these genomic data can be integrated as a comprehensive feature source for cancer clustering. How to establish an effective clustering model for comprehensive analysis of integrated TCGA data has become a key issue. In this paper, we develop the traditional LRR method and propose a novel method named Block-constraint Laplacian-Regularized Low-Rank Representation (BLLRR) to model multigenome data for cancer sample clustering. The proposed method is dedicated to extracting more abundant subspace structure information from multiple genomic data to improve the accuracy of cancer sample clustering. Considering the heterogeneity of different genome data, we introduce the block-constraint idea into our method. In BLLRR decomposition, we treat each genome data as a data block and impose different constraints on different data blocks. In addition, graph Laplacian is also introduced into our method to better learn the topological structure of data by preserving the local geometric information. The experiments demonstrate that the BLLRR method can effectively analyze integrated TCGA data and extract more subspace structure information from multigenome data. It is a reliable and efficient clustering algorithm for cancer sample clustering.

Non-negative matrix factorization (NMF) is a matrix decomposition method based on the square loss function. To exploit cancer information, cancer gene expression data often uses the NMF method to reduce dimensionality. Gene expression data usually have some noise and outliers, while the original NMF loss function is very sensitive to non-Gaussian noise. To improve the robustness and clustering performance of the algorithm, we propose a sparse graph regularization NMF based on Huber loss model for cancer data analysis (Huber-SGNMF). Huber loss is a function between L1-norm and L2-norm that can effectively handle non-Gaussian noise and outliers. Taking into account the sparsity matrix and data geometry information, sparse penalty and graph regularization terms are introduced into the model to enhance matrix sparsity and capture data manifold structure. Before the experiment, we first analyzed the robustness of Huber-SGNMF and other models. Experiments on The Cancer Genome Atlas (TCGA) data have shown that Huber-SGNMF performs better than other most advanced methods in sample clustering and differentially expressed gene selection.

Sparse spectral clustering (SSC) has become one of the most popular clustering approaches in recent years. However, its high computational complexity prevents its application to large-scale datasets such as hyperspectral images (HSIs). In this paper, we propose two efficient approximate sparse spectral clustering methods for HSIs clustering in which clustering performance is improved by utilizing local information among the data. Firstly, we construct a smaller representative dataset on which sparse spectral clustering is performed. Then the labels of ground object are extending to whole dataset based on the local information according to two extending strategies. The first one is that the local interpolation is utilized to improve the extension of the clustering result. The other one is that the label extension is turned to a problem of subspace embedding, and is fulfilled by locally linear embedding (LLE). Several experiments on HSIs demonstrated that the proposed algorithms are effective for HSIs clustering.

Integration of multi-omics data of cancer can help people to explore cancers comprehensively. However, with a large volume of different omics and functional data being generated, there is a major challenge to distinguish functional driver genes from a sea of inconsequential passenger genes that accrue stochastically but do not contribute to cancer development. In this paper, we present a gene length-based network method, named DriverFinder, to identify driver genes by integrating somatic mutations, copy number variations, gene-gene interaction network, tumor expression, and normal expression data. To illustrate the performance of DriverFinder, it is applied to four cancer types from The Cancer Genome Atlas including breast cancer, head and neck squamous cell carcinoma, thyroid carcinoma, and kidney renal clear cell carcinoma. Compared with some conventional methods, the results demonstrate that the proposed method is effective. Moreover, it can decrease the influence of gene length in identifying driver genes and identify some rare mutated driver genes.

Differential expression plays an important role in cancer diagnosis and classification. In recent years, many methods have been used to identify differentially expressed genes. However, the recognition rate and reliability of gene selection still need to be improved. In this paper, a novel constrained method named robust nonnegative matrix factorization via joint graph Laplacian and discriminative information (GLD-RNMF) is proposed for identifying differentially expressed genes, in which manifold learning and the discriminative label information are incorporated into the traditional nonnegative matrix factorization model to train the objective matrix. Specifically, L2,1-norm minimization is enforced on both the error function and the regularization term which is robust to outliers and noise in gene data. Furthermore, the multiplicative update rules and the details of convergence proof are shown for the new model. The experimental results on two publicly available cancer datasets demonstrate that GLD-RNMF is an effective method for identifying differentially expressed genes.

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.

In this paper, based on low-rank representation and eigenface extraction, we present an improvement to the well known Sparse Representation based Classification (SRC). Firstly, the low-rank images of the face images of each individual in training subset are extracted by the Robust Principal Component Analysis (Robust PCA) to alleviate the influence of noises (e.g., illumination difference and occlusions). Secondly, Singular Value Decomposition (SVD) is applied to extract the eigenfaces from these low-rank and approximate images. Finally, we utilize these eigenfaces to construct a compact and discriminative dictionary for sparse representation. We evaluate our method on five popular databases. Experimental results demonstrate the effectiveness and robustness of our method.

The one-sample-per-person problem has become an active research topic for face recognition in recent years because of its challenges and significance for real-world applications. However, achieving relatively higher recognition accuracy is still a difficult problem due to, usually, too few training samples being available and variations of illumination and expression. To alleviate the negative effects caused by these unfavorable factors, in this paper we propose a more accurate spectral feature image-based 2DLDA (two-dimensional linear discriminant analysis) ensemble algorithm for face recognition, with one sample image per person. In our algorithm, multi-resolution spectral feature images are constructed to represent the face images; this can greatly enlarge the training set. The proposed method is inspired by our finding that, among these spectral feature images, features extracted from some orientations and scales using 2DLDA are not sensitive to variations of illumination and expression. In order to maintain the positive characteristics of these filters and to make correct category assignments, the strategy of classifier committee learning (CCL) is designed to combine the results obtained from different spectral feature images. Using the above strategies, the negative effects caused by those unfavorable factors can be alleviated efficiently in face recognition. Experimental results on the standard databases demonstrate the feasibility and efficiency of the proposed method.

Identifying subspace gene clusters from the gene expression data is useful for discovering novel functional gene interactions. In this paper, we propose to use low-rank representation (LRR) to identify the subspace gene clusters from microarray data. LRR seeks the lowest-rank representation among all the candidates that can represent the genes as linear combinations of the bases in the dataset. The clusters can be extracted based on the block diagonal representation matrix obtained using LRR, and they can well capture the intrinsic patterns of genes with similar functions. Meanwhile, the parameter of LRR can balance the effect of noise so that the method is capable of extracting useful information from the data with high level of background noise. Compared with traditional methods, our approach can identify genes with similar functions yet without similar expression profiles. Also, it could assign one gene into different clusters. Moreover, our method is robust to the noise and can identify more biologically relevant gene clusters. When applied to three public datasets, the results show that the LRR based method is superior to existing methods for identifying subspace gene clusters.

Conventional gene selection methods based on principal component analysis (PCA) use only the first principal component (PC) of PCA or sparse PCA to select characteristic genes. These methods indeed assume that the first PC plays a dominant role in gene selection. However, in a number of cases this assumption is not satisfied, so the conventional PCA-based methods usually provide poor selection results. In order to improve the performance of the PCA-based gene selection method, we put forward the gene selection method via weighting PCs by singular values (WPCS). Because different PCs have different importance, the singular values are exploited as the weights to represent the influence on gene selection of different PCs. The ROC curves and AUC statistics on artificial data show that our method outperforms the state-of-the-art methods. Moreover, experimental results on real gene expression data sets show that our method can extract more characteristic genes in response to abiotic stresses than conventional gene selection methods.