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Identifying cancer subtypes by integration of multi-omic data is beneficial to improve the understanding of disease progression, and provides more precise treatment for patients. Cancer subtypes identification is usually accomplished by clustering patients with unsupervised learning approaches. Thus, most existing integrative cancer subtyping methods are performed in an entirely unsupervised way. An integrative cancer subtyping approach can be improved to discover clinically more relevant cancer subtypes when considering the clinical survival response variables. In this study, we propose a Survival Supervised Graph Clustering (S2GC)for cancer subtyping by taking into consideration survival information. Specifically, we use a graph to represent similarity of patients, and develop a multi-omic survival analysis embedding with patient-to-patient similarity graph learning for cancer subtype identification. The multi-view (omic)survival analysis model and graph of patients are jointly learned in a unified way. The learned optimal graph can be unitized to cluster cancer subtypes directly. In the proposed model, the survival analysis model and adaptive graph learning could positively reinforce each other. Consequently, the survival time can be considered as supervised information to improve the quality of the similarity graph and explore clinically more relevant subgroups of patients. Experiments on several representative multi-omic cancer datasets demonstrate that the proposed method achieves better results than a number of state-of-the-art methods. The results also suggest that our method is able to identify biologically meaningful subgroups for different cancer types. (Our Matlab source code is available online at github: https://github.com/CLiu272/S2GC) [ABSTRACT FROM AUTHOR]

Conventional semi-supervised clustering approaches have several shortcomings, such as (1) not fully utilizing all useful must-link and cannot-link constraints, (2) not considering how to deal with high dimensional data with noise, and (3) not fully addressing the need to use an adaptive process to further improve the performance of the algorithm. In this paper, we first propose the transitive closure based constraint propagation approach, which makes use of the transitive closure operator and the affinity propagation to address the first limitation. Then, the random subspace based semi-supervised clustering ensemble framework with a set of proposed confidence factors is designed to address the second limitation and provide more stable, robust, and accurate results. Next, the adaptive semi-supervised clustering ensemble framework is proposed to address the third limitation, which adopts a newly designed adaptive process to search for the optimal subspace set. Finally, we adopt a set of nonparametric tests to compare different semi-supervised clustering ensemble approaches over multiple datasets. The experimental results on 20 real high dimensional cancer datasets with noisy genes and 10 datasets from UCI datasets and KEEL datasets show that (1) The proposed approaches work well on most of the real-world datasets. (2) It outperforms other state-of-the-art approaches on 12 out of 20 cancer datasets, and 8 out of 10 UCI machine learning datasets. [ABSTRACT FROM PUBLISHER]

Traditional cluster ensemble approaches have three limitations: ($1$ ) They do not make use of prior knowledge of the datasets given by experts. ($2$ ) Most of the conventional cluster ensemble methods cannot obtain satisfactory results when handling high dimensional data. ( $3$) All the ensemble members are considered, even the ones without positive contributions. In order to address the limitations of conventional cluster ensemble approaches, we first propose an incremental semi-supervised clustering ensemble framework (ISSCE) which makes use of the advantage of the random subspace technique, the constraint propagation approach, the proposed incremental ensemble member selection process, and the normalized cut algorithm to perform high dimensional data clustering. The random subspace technique is effective for handling high dimensional data, while the constraint propagation approach is useful for incorporating prior knowledge. The incremental ensemble member selection process is newly designed to judiciously remove redundant ensemble members based on a newly proposed local cost function and a global cost function, and the normalized cut algorithm is adopted to serve as the consensus function for providing more stable, robust, and accurate results. Then, a measure is proposed to quantify the similarity between two sets of attributes, and is used for computing the local cost function in ISSCE. Next, we analyze the time complexity of ISSCE theoretically. Finally, a set of nonparametric tests are adopted to compare multiple semi-supervised clustering ensemble approaches over different datasets. The experiments on 18 real-world datasets, which include six UCI datasets and 12 cancer gene expression profiles, confirm that ISSCE works well on datasets with very high dimensionality, and outperforms the state-of-the-art semi-supervised clustering ensemble approaches. [ABSTRACT FROM PUBLISHER]

Transcription factor binding sites (TFBSs) are relatively short (5-15 bp) and degenerate. Identifying them is a computationally challenging task. In particular, protein binding microarray (PBM) is a high-throughput platform that can measure the DNA binding preference of a protein in a comprehensive and unbiased manner; for instance, a typical PBM experiment can measure binding signal intensities of a protein to all possible DNA k-mers ( $k = 8\sim$ 10). Since proteins can often bind to DNA with different binding intensities, one of the major challenges is to build TFBS (also known as DNA motif) models which can fully capture the quantitative binding affinity data. To learn DNA motif models from the non-convex objective function landscape, several optimization methods are compared and applied to the PBM motif model building problem. In particular, representative methods from different optimization paradigms have been chosen for modeling performance comparison on hundreds of PBM datasets. The results suggest that the multimodal optimization methods are very effective for capturing the binding preference information from PBM data. In particular, we observe a general performance improvement if choosing di-nucleotide modeling over mono-nucleotide modeling. In addition, the models learned by the best-performing method are applied to two independent applications: PBM probe rotation testing and ChIP-Seq peak sequence prediction, demonstrating its biological applicability. [ABSTRACT FROM PUBLISHER]

Performing clustering analysis is one of the important research topics in cancer discovery using gene expression profiles, which is crucial in facilitating the successful diagnosis and treatment of cancer. While there are quite a number of research works which perform tumor clustering, few of them considers how to incorporate fuzzy theory together with an optimization process into a consensus clustering framework to improve the performance of clustering analysis. In this paper, we first propose a random double clustering based cluster ensemble framework (RDCCE) to perform tumor clustering based on gene expression data. Specifically, RDCCE generates a set of representative features using a randomly selected clustering algorithm in the ensemble, and then assigns samples to their corresponding clusters based on the grouping results. In addition, we also introduce the random double clustering based fuzzy cluster ensemble framework (RDCFCE), which is designed to improve the performance of RDCCE by integrating the newly proposed fuzzy extension model into the ensemble framework. RDCFCE adopts the normalized cut algorithm as the consensus function to summarize the fuzzy matrices generated by the fuzzy extension models, partition the consensus matrix, and obtain the final result. Finally, adaptive RDCFCE (A-RDCFCE) is proposed to optimize RDCFCE and improve the performance of RDCFCE further by adopting a self-evolutionary process (SEPP) for the parameter set. Experiments on real cancer gene expression profiles indicate that RDCFCE and A-RDCFCE works well on these data sets, and outperform most of the state-of-the-art tumor clustering algorithms. [ABSTRACT FROM PUBLISHER]

Tumor clustering is one of the important techniques for tumor discovery from cancer gene expression profiles, which is useful for the diagnosis and treatment of cancer. While different algorithms have been proposed for tumor clustering, few make use of the expert’s knowledge to better the performance of tumor discovery. In this paper, we first view the expert’s knowledge as constraints in the process of clustering, and propose a feature selection based semi-supervised cluster ensemble framework (FS-SSCE) for tumor clustering from bio-molecular data. Compared with traditional tumor clustering approaches, the proposed framework FS-SSCE is featured by two properties: (1) The adoption of feature selection techniques to dispel the effect of noisy genes. (2) The employment of the binate constraint based K-means algorithm to take into account the effect of experts’ knowledge. Then, a double selection based semi-supervised cluster ensemble framework (DS-SSCE) which not only applies the feature selection technique to perform gene selection on the gene dimension, but also selects an optimal subset of representative clustering solutions in the ensemble and improve the performance of tumor clustering using the normalized cut algorithm. DS-SSCE also introduces a confidence factor into the process of constructing the consensus matrix by considering the prior knowledge of the data set. Finally, we design a modified double selection based semi-supervised cluster ensemble framework (MDS-SSCE) which adopts multiple clustering solution selection strategies and an aggregated solution selection function to choose an optimal subset of clustering solutions. The results in the experiments on cancer gene expression profiles show that ($\rm i$) FS-SSCE, DS-SSCE and MDS-SSCE are suitable for performing tumor clustering from bio-molecular data. ( $\rm ii$) MDS-SSCE outperforms a number of state-of-the-art tumor clustering approaches on most of the data sets. [ABSTRACT FROM PUBLISHER]

In order to perform successful diagnosis and treatment of cancer, discovering, and classifying cancer types correctly is essential. One of the challenging properties of class discovery from cancer data sets is that cancer gene expression profiles not only include a large number of genes, but also contains a lot of noisy genes. In order to reduce the effect of noisy genes in cancer gene expression profiles, we propose two new consensus clustering frameworks, named as triple spectral clustering-based consensus clustering (SC^3) and double spectral clustering-based consensus clustering (SC^2Ncut) in this paper, for cancer discovery from gene expression profiles. SC^3 integrates the spectral clustering (SC) algorithm multiple times into the ensemble framework to process gene expression profiles. Specifically, spectral clustering is applied to perform clustering on the gene dimension and the cancer sample dimension, and also used as the consensus function to partition the consensus matrix constructed from multiple clustering solutions. Compared with SC^3, SC^2Ncut adopts the normalized cut algorithm, instead of spectral clustering, as the consensus function. Experiments on both synthetic data sets and real cancer gene expression profiles illustrate that the proposed approaches not only achieve good performance on gene expression profiles, but also outperforms most of the existing approaches in the process of class discovery from these profiles. [ABSTRACT FROM PUBLISHER]

Abstract: Recently, researchers are focusing more on the study of support vector machine (SVM) due to its useful applications in a number of areas, such as pattern recognition, multimedia, image processing and bioinformatics. One of the main research issues is how to improve the efficiency of the original SVM model, while preventing any deterioration of the classification performance of the model. In this paper, we propose a modified SVM based on the properties of support vectors and a pruning strategy to preserve support vectors, while eliminating redundant training vectors at the same time. The experiments on real images show that (1) our proposed approach can reduce the number of input training vectors, while preserving the support vectors, which leads to a significant reduction in the computational cost while attaining similar levels of accuracy. (2)The approach also works well when applied to image segmentation. [ABSTRACT FROM AUTHOR]

Feature selection is widely established as one of the fundamental computational techniques in mining microarray data. Due to the lack of categorized information in practice, unsupervised feature selection is more practically important but correspondingly more difficult. Motivated by the cluster ensemble techniques, which combine multiple clustering solutions into a consensus solution of higher accuracy and stability, recent efforts in unsupervised feature selection proposed to use these consensus solutions as oracles. However, these methods are dependent on both the particular cluster ensemble algorithm used and the knowledge of the true cluster number. These methods will be unsuitable when the true cluster number is not available, which is common in practice. In view of the above problems, a new unsupervised feature ranking method is proposed to evaluate the importance of the features based on consensus affinity. Different from previous works, our method compares the corresponding affinity of each feature between a pair of instances based on the consensus matrix of clustering solutions. As a result, our method alleviates the need to know the true number of clusters and the dependence on particular cluster ensemble approaches as in previous works. Experiments on real gene expression data sets demonstrate significant improvement of the feature ranking results when compared to several state-of-the-art techniques. [ABSTRACT FROM PUBLISHER]

There are not many classifier ensemble approaches which investigate the data sample space and the feature space at the same time, and this multi-pronged approach will be helpful for constructing more powerful learning models. For example, the AdaBoost approach only investigates the data sample space, while the random subspace technique only focuses on the feature space. To address this limitation, we propose the progressive subspace ensemble learning approach (PSEL) which takes into account the data sample space and the feature space at the same time. Specifically, PSEL first adopts the random subspace technique to generate a set of subspaces. Then, a progressive selection process based on new cost functions that incorporate current and long-term information to select the classifiers sequentially will be introduced. Finally, a weighted voting scheme is used to summarize the predicted labels and obtain the final result. We also adopt a number of non-parametric tests to compare PSEL and its competitors over multiple datasets. The results of the experiments show that PSEL works well on most of the real datasets, and outperforms a number of state-of-the-art classifier ensemble approaches. [ABSTRACT FROM AUTHOR]