A multiobjective multi-view cluster ensemble technique: Application in patient subclassification.
TL;DR: A late integration based multiobjective multi-view clustering algorithm which uses a special perturbation operator to generate a single set of non-dominated solutions for patient sub-classification of multi-omics datasets.
Abstract: Recent high throughput omics technology has been used to assemble large biomedical omics datasets. Clustering of single omics data has proven invaluable in biomedical research. For the task of patient sub-classification, all the available omics data should be utilized combinedly rather than treating them individually. Clustering of multi-omics datasets has the potential to reveal deep insights. Here, we propose a late integration based multiobjective multi-view clustering algorithm which uses a special perturbation operator. Initially, a large number of diverse clustering solutions (called base partitionings) are generated for each omic dataset using four clustering algorithms, viz., k means, complete linkage, spectral and fast search clustering. These base partitionings of multi-omic datasets are suitably combined using a special perturbation operator. The perturbation operator uses an ensemble technique to generate new solutions from the base partitionings. The optimal combination of multiple partitioning solutions across different views is determined after optimizing the objective functions, namely conn-XB, for checking the quality of partitionings for different views, and agreement index, for checking agreement between the views. The search capability of a multiobjective simulated annealing approach, namely AMOSA is used for this purpose. Lastly, the non-dominated solutions of the different views are combined based on similarity to generate a single set of non-dominated solutions. The proposed algorithm is evaluated on 13 multi-view cancer datasets. An elaborated comparative study with several baseline methods and five state-of-the-art models is performed to show the effectiveness of the algorithm.
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TL;DR: In this article, a review of the available data integration strategies for single-cell multi-omics data integration is presented, including early, intermediate, and late data integration approaches, as well as the challenges and prospective future directions of singlecell multomic data integration, including examples of adopting multi-view analysis approaches used in other disciplines.
Abstract: Single-cell omics technologies are currently solving biological and medical problems that earlier have remained elusive, such as discovery of new cell types, cellular differentiation trajectories and communication networks across cells and tissues. Current advances especially in single-cell multi-omics hold high potential for breakthroughs by integration of multiple different omics layers. To pair with the recent biotechnological developments, many computational approaches to process and analyze single-cell multi-omics data have been proposed. In this review, we first introduce recent developments in single-cell multi-omics in general and then focus on the available data integration strategies. The integration approaches are divided into three categories: early, intermediate, and late data integration. For each category, we describe the underlying conceptual principles and main characteristics, as well as provide examples of currently available tools and how they have been applied to analyze single-cell multi-omics data. Finally, we explore the challenges and prospective future directions of single-cell multi-omics data integration, including examples of adopting multi-view analysis approaches used in other disciplines to single-cell multi-omics.
26 citations
TL;DR: In this paper, five unsupervised machine learning (ML) methods were compared in terms of clinical and biological characteristics of breast cancer patients with an indication for adjuvant chemotherapy between 2013 and 2016.
Abstract: Genomics and transcriptomics have led to the widely-used molecular classification of breast cancer (BC). However, heterogeneous biological behaviors persist within breast cancer subtypes. Metabolomics is a rapidly-expanding field of study dedicated to cellular metabolisms affected by the environment. The aim of this study was to compare metabolomic signatures of BC obtained by 5 different unsupervised machine learning (ML) methods. Fifty-two consecutive patients with BC with an indication for adjuvant chemotherapy between 2013 and 2016 were retrospectively included. We performed metabolomic profiling of tumor resection samples using liquid chromatography-mass spectrometry. Here, four hundred and forty-nine identified metabolites were selected for further analysis. Clusters obtained using 5 unsupervised ML methods (PCA k-means, sparse k-means, spectral clustering, SIMLR and k-sparse) were compared in terms of clinical and biological characteristics. With an optimal partitioning parameter k = 3, the five methods identified three prognosis groups of patients (favorable, intermediate, unfavorable) with different clinical and biological profiles. SIMLR and K-sparse methods were the most effective techniques in terms of clustering. In-silico survival analysis revealed a significant difference for 5-year predicted OS between the 3 clusters. Further pathway analysis using the 449 selected metabolites showed significant differences in amino acid and glucose metabolism between BC histologic subtypes. Our results provide proof-of-concept for the use of unsupervised ML metabolomics enabling stratification and personalized management of BC patients. The design of novel computational methods incorporating ML and bioinformatics techniques should make available tools particularly suited to improving the outcome of cancer treatment and reducing cancer-related mortalities.
19 citations
TL;DR: This paper proposes a framework to increase the embedding capacity of reversible data hiding techniques that use a difference of image to embed data by rearranging the columns (or rows) of the image in a way that enhances the smooth regions of an image.
Abstract: Reversible Data Hiding (RDH) techniques have gained popularity over the last two decades, where data is embedded in an image in such a way that the original image can be restored. Earlier works on RDH was based on the Image Histogram Modification that uses the peak point to embed data in the image. More recent works focus on the Difference Image Histogram Modification that exploits the fact that the neighbouring pixels of an image are highly correlated and therefore the difference of image makes more space to embed large amount of data. In this paper we propose a framework to increase the embedding capacity of reversible data hiding techniques that use a difference of image to embed data. The main idea is that, instead of taking the difference of the neighboring pixels, we rearrange the columns (or rows) of the image in a way that enhances the smooth regions of an image. Any difference based technique to embed data can then be used in the transformed image. The proposed method is applied on different types of images including textures, patterns and publicly available images. Experimental results demonstrate that the proposed method not only increases the message embedding capacity of a given image by more than 50% but also the visual quality of the marked image containing the message is more than the visual quality obtained by existing state-of-the-art reversible data hiding technique. The proposed technique is also verified by Pixel Difference Histogram (PDH) Stegoanalysis and results demonstrate that marked images generated by proposed method is undetectable by PDH analysis.
18 citations
TL;DR: The proposed methodology, Multi-view Neighbourhood Embedding (MvNE), shows an improvement of approximately 2−3% over state-of-the-art models when evaluated on 10 omics data sets.
Abstract: In real world applications, data sets are often comprised of multiple views, which provide consensus and complementary information to each other. Embedding learning is an effective strategy for nearest neighbour search and dimensionality reduction in large data sets. This paper attempts to learn a unified probability distribution of the points across different views and generates a unified embedding in a low-dimensional space to optimally preserve neighbourhood identity. Probability distributions generated for each point for each view are combined by conflation method to create a single unified distribution. The goal is to approximate this unified distribution as much as possible when a similar operation is performed on the embedded space. As a cost function, the sum of Kullback-Leibler divergence over the samples is used, which leads to a simple gradient adjusting the position of the samples in the embedded space. The proposed methodology can generate embedding from both complete and incomplete multi-view data sets. Finally, a multi-objective clustering technique (AMOSA) is applied to group the samples in the embedded space. The proposed methodology, Multi-view Neighbourhood Embedding (MvNE), shows an improvement of approximately 2−3% over state-of-the-art models when evaluated on 10 omics data sets.
12 citations
TL;DR: The past, present and future of clinical biomarker development is discussed, including the identification of physicochemical assays, current regulations, the development and reproducibility of clinical trials, as well as the revolution of omics technologies and state-of-the-art integration and analysis approaches.
Abstract: In this chapter we discuss the past, present and future of clinical biomarker development. We explore the advent of new technologies, paving the way in which health, medicine and disease is understood. This review includes the identification of physicochemical assays, current regulations, the development and reproducibility of clinical trials, as well as, the revolution of omics technologies and state-of-the-art integration and analysis approaches.
12 citations
References
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TL;DR: An overview of pattern clustering methods from a statistical pattern recognition perspective is presented, with a goal of providing useful advice and references to fundamental concepts accessible to the broad community of clustering practitioners.
Abstract: Clustering is the unsupervised classification of patterns (observations, data items, or feature vectors) into groups (clusters). The clustering problem has been addressed in many contexts and by researchers in many disciplines; this reflects its broad appeal and usefulness as one of the steps in exploratory data analysis. However, clustering is a difficult problem combinatorially, and differences in assumptions and contexts in different communities has made the transfer of useful generic concepts and methodologies slow to occur. This paper presents an overview of pattern clustering methods from a statistical pattern recognition perspective, with a goal of providing useful advice and references to fundamental concepts accessible to the broad community of clustering practitioners. We present a taxonomy of clustering techniques, and identify cross-cutting themes and recent advances. We also describe some important applications of clustering algorithms such as image segmentation, object recognition, and information retrieval.
14,054 citations
TL;DR: A generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case and suggests a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
Abstract: Although cancer classification has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery) or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case. A class discovery procedure automatically discovered the distinction between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) without previous knowledge of these classes. An automatically derived class predictor was able to determine the class of new leukemia cases. The results demonstrate the feasibility of cancer classification based solely on gene expression monitoring and suggest a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
12,530 citations
Harvard University1, University of North Carolina at Chapel Hill2, University of California, Berkeley3, Washington University in St. Louis4, Lawrence Berkeley National Laboratory5, University of California, San Francisco6, Mayo Clinic7, Memorial Sloan Kettering Cancer Center8, SRA International9, Walter and Eliza Hall Institute of Medical Research10
TL;DR: A robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes is described and multidimensional genomic data is integrated to establish patterns of somatic mutations and DNA copy number.
5,764 citations
Harvard University1, University of North Carolina at Chapel Hill2, University of California, Berkeley3, Washington University in St. Louis4, Lawrence Berkeley National Laboratory5, University of California, San Francisco6, Mayo Clinic7, Memorial Sloan Kettering Cancer Center8, SRA International9, Walter and Eliza Hall Institute of Medical Research10
TL;DR: The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM) and proposed a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes as discussed by the authors.
Abstract: The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.
4,464 citations
TL;DR: This paper introduces the problem of combining multiple partitionings of a set of objects into a single consolidated clustering without accessing the features or algorithms that determined these partitionings and proposes three effective and efficient techniques for obtaining high-quality combiners (consensus functions).
Abstract: This paper introduces the problem of combining multiple partitionings of a set of objects into a single consolidated clustering without accessing the features or algorithms that determined these partitionings. We first identify several application scenarios for the resultant 'knowledge reuse' framework that we call cluster ensembles. The cluster ensemble problem is then formalized as a combinatorial optimization problem in terms of shared mutual information. In addition to a direct maximization approach, we propose three effective and efficient techniques for obtaining high-quality combiners (consensus functions). The first combiner induces a similarity measure from the partitionings and then reclusters the objects. The second combiner is based on hypergraph partitioning. The third one collapses groups of clusters into meta-clusters which then compete for each object to determine the combined clustering. Due to the low computational costs of our techniques, it is quite feasible to use a supra-consensus function that evaluates all three approaches against the objective function and picks the best solution for a given situation. We evaluate the effectiveness of cluster ensembles in three qualitatively different application scenarios: (i) where the original clusters were formed based on non-identical sets of features, (ii) where the original clustering algorithms worked on non-identical sets of objects, and (iii) where a common data-set is used and the main purpose of combining multiple clusterings is to improve the quality and robustness of the solution. Promising results are obtained in all three situations for synthetic as well as real data-sets.
4,375 citations