scholarly journals One-Step Robust Low-Rank Subspace Segmentation for Tumor Sample Clustering

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Jian Liu ◽  
Yuhu Cheng ◽  
Xuesong Wang ◽  
Shuguang Ge

Clustering of tumor samples can help identify cancer types and discover new cancer subtypes, which is essential for effective cancer treatment. Although many traditional clustering methods have been proposed for tumor sample clustering, advanced algorithms with better performance are still needed. Low-rank subspace clustering is a popular algorithm in recent years. In this paper, we propose a novel one-step robust low-rank subspace segmentation method (ORLRS) for clustering the tumor sample. For a gene expression data set, we seek its lowest rank representation matrix and the noise matrix. By imposing the discrete constraint on the low-rank matrix, without performing spectral clustering, ORLRS learns the cluster indicators of subspaces directly, i.e., performing the clustering task in one step. To improve the robustness of the method, capped norm is adopted to remove the extreme data outliers in the noise matrix. Furthermore, we conduct an efficient solution to solve the problem of ORLRS. Experiments on several tumor gene expression data demonstrate the effectiveness of ORLRS.

Author(s):  
Prangyaparamita Mohapatra ◽  
Tripti Swarnkar

DNA microarray technology has made it possible to simultaneously monitor the expression levels of thousands of genes during biological processes and across collections of related samples. However, the large number of genes and the complexity of biological networks greatly increase the challenges of comprehending and interpreting the resulting mass of data, which often consists of millions of measurements. A first step toward addressing this challenge is the use of clustering techniques, which is essential in the data mining process to reveal natural structures and identify interesting patterns in the underlying data. Cluster analysis seeks to partition a given data set into groups based on specified features so that the data points within a group are more similar to each other than the points in different groups. Many conventional clustering algorithms have been adapted or directly applied to gene expression data, and also new algorithms have recently been proposed specifically aiming at gene expression data. These clustering algorithms have been proven useful for identifying biologically relevant groups of genes and samples. A large number of clustering approaches have been proposed for the analysis of gene expression data obtained from microarray experiments. However, the results of the application of standard clustering methods to genes are limited. These limited results are imposed by the existence of a number of experimental conditions where the activity of genes is uncorrelated. A similar limitation exists when clustering of conditions is performed. For this reason, a number of algorithms that perform simultaneous clustering on the row and column dimensions of the gene expression matrix have been proposed to date. This simultaneous clustering, usually designated by biclustering, seeks to find submatrices that are subgroups of genes and subgroups of columns, where the genes exhibit highly correlated activities for every condition. This type of algorithms has also been proposed and used in other fields, such as information retrieval and data mining. In this paper, we first briefly introduce the concepts of microarray technology and discuss the basic elements of clustering on gene expression data. Then, we present specific challenges pertinent to each clustering category and introduce several representative approaches.


2000 ◽  
Vol 3 (1) ◽  
pp. 9-15 ◽  
Author(s):  
PETER J. WOOLF ◽  
YIXIN WANG

Woolf, Peter J., and Yixin Wang. A fuzzy logic approach to analyzing gene expression data. Physiol Genomics 3: 9–15, 2000.—We have developed a novel algorithm for analyzing gene expression data. This algorithm uses fuzzy logic to transform expression values into qualitative descriptors that can be evaluated by using a set of heuristic rules. In our tests we designed a model to find triplets of activators, repressors, and targets in a yeast gene expression data set. For the conditions tested, the predictions made by the algorithm agree well with experimental data in the literature. The algorithm can also assist in determining the function of uncharacterized proteins and is able to detect a substantially larger number of transcription factors than could be found at random. This technology extends current techniques such as clustering in that it allows the user to generate a connected network of genes using only expression data.


Author(s):  
Soumya Raychaudhuri

The most interesting and challenging gene expression data sets to analyze are large multidimensional data sets that contain expression values for many genes across multiple conditions. In these data sets the use of scientific text can be particularly useful, since there are a myriad of genes examined under vastly different conditions, each of which may induce or repress expression of the same gene for different reasons. There is an enormous complexity to the data that we are examining—each gene is associated with dozens if not hundreds of expression values as well as multiple documents built up from vocabularies consisting of thousands of words. In Section 2.4 we reviewed common gene expression strategies, most of which revolve around defining groups of genes based on common profiles. A limitation of many gene expression analytic approaches is that they do not incorporate comprehensive background knowledge about the genes into the analysis. We present computational methods that leverage the peer-reviewed literature in the automatic analysis of gene expression data sets. Including the literature in gene expression data analysis offers an opportunity to incorporate background functional information about the genes when defining expression clusters. In Chapter 5 we saw how literature- based approaches could help in the analysis of single condition experiments. Here we will apply the strategies introduced in Chapter 6 to assess the coherence of groups of genes to enhance gene expression analysis approaches. The methods proposed here could, in fact, be applied to any multivariate genomics data type. The key concepts discussed in this chapter are listed in the frame box. We begin with a discussion of gene groups and their role in expression analysis; we briefly discuss strategies to assign keywords to groups and strategies to assess their functional coherence. We apply functional coherence measures to gene expression analysis; for examples we focus on a yeast expression data set. We first demonstrate how functional coherence can be used to focus in on the key biologically relevant gene groups derived by clustering methods such as self-organizing maps and k-means clustering.


2019 ◽  
Vol 21 (5) ◽  
pp. 1818-1824 ◽  
Author(s):  
Qi Zhao ◽  
Yu Sun ◽  
Zekun Liu ◽  
Hongwan Zhang ◽  
Xingyang Li ◽  
...  

Abstract   Unsupervised clustering of high-throughput gene expression data is widely adopted for cancer subtyping. However, cancer subtypes derived from a single dataset are usually not applicable across multiple datasets from different platforms. Merging different datasets is necessary to determine accurate and applicable cancer subtypes but is still embarrassing due to the batch effect. CrossICC is an R package designed for the unsupervised clustering of gene expression data from multiple datasets/platforms without the requirement of batch effect adjustment. CrossICC utilizes an iterative strategy to derive the optimal gene signature and cluster numbers from a consensus similarity matrix generated by consensus clustering. This package also provides abundant functions to visualize the identified subtypes and evaluate subtyping performance. We expected that CrossICC could be used to discover the robust cancer subtypes with significant translational implications in personalized care for cancer patients. Availability and Implementation The package is implemented in R and available at GitHub (https://github.com/bioinformatist/CrossICC) and Bioconductor (http://bioconductor.org/packages/release/bioc/html/CrossICC.html) under the GPL v3 License.


2019 ◽  
Vol 20 (S22) ◽  
Author(s):  
Juan Wang ◽  
Cong-Hai Lu ◽  
Jin-Xing Liu ◽  
Ling-Yun Dai ◽  
Xiang-Zhen Kong

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


2007 ◽  
Vol 1 (S1) ◽  
Author(s):  
Alfonso Buil ◽  
Alexandre Perera-Lluna ◽  
Ramon Souto ◽  
Juan M Peralta ◽  
Laura Almasy ◽  
...  

IEEE Access ◽  
2019 ◽  
Vol 7 ◽  
pp. 22086-22095 ◽  
Author(s):  
Jing Xu ◽  
Peng Wu ◽  
Yuehui Chen ◽  
Qingfang Meng ◽  
Hussain Dawood ◽  
...  

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2663-2663
Author(s):  
Matthew A Care ◽  
Stephen M Thirdborough ◽  
Andrew J Davies ◽  
Peter W.M. Johnson ◽  
Andrew Jack ◽  
...  

Abstract Purpose To assess whether comparative gene network analysis can reveal characteristic immune response signatures that predict clinical response in Diffuse large B-cell lymphoma (DLBCL). Background The wealth of available gene expression data sets for DLBCL and other cancer types provides a resource to define recurrent pathological processes at the level of gene expression and gene correlation neighbourhoods. This is of particular relevance in the context of cancer immune responses, where convergence onto common patterns may drive shared gene expression profiles. Where existing and novel immunotherapies harness the immune response for therapeutic benefit such responses may provide predictive biomarkers. Methods We independently analysed publically available DLBCL gene expression data sets and a wide compendium of gene expression data from diverse cancer types, and then asked whether common elements of cancer host response could be identified from resulting networks. Using 10 DLBCL gene expression data sets, encompassing 2030 cases, we established pairwise gene correlation matrices per data set, which were merged to generate median correlations of gene pairs across all data sets. Gene network analysis and unsupervised clustering was then applied to define global representations of DLBCL gene expression neighbourhoods. In parallel a diverse range of solid and lymphoid malignancies including; breast, colorectal, oesophageal, head and neck, non-small cell lung, prostate, pancreatic cancer, Hodgkin lymphoma, Follicular lymphoma and DLBCL were independently analysed using an orthogonal weighted gene correlation network analysis of gene expression data sets from which correlated modules across diverse cancer types were identified. The biology of resulting gene neighbourhoods was assessed by signature and ontology enrichment, and the overlap between gene correlation neighbourhoods and WGCNA derived modules associated with immune/host responses was analysed. Results Amongst DLBCL data, we identified distinct gene correlation neighbourhoods associated with the immune response. These included both elements of IFN-polarised responses, core T-cell, and cytotoxic signatures as well as distinct macrophage responses. Neighbourhoods linked to macrophages separated CD163 from CD68 and CD14. In the WGCNA analysis of diverse cancer types clusters corresponding to these immune response neighbourhoods were independently identified including a highly similar cluster related to CD163. The overlapping CD163 clusters in both analyses linked to diverse Fc-Receptors, complement pathway components and patterns of scavenger receptors potentially linked to alternative macrophage activation. The relationship between the CD163 macrophage gene expression cluster and outcome was tested in DLBCL data sets, identifying a poor response in CD163 -cluster high patients, which reached statistical significance in one data set (GSE10846). Notably, the effect of the CD163-associated gene neighbourhood which correlates with poor outcome post rituximab containing immunochemotherapy is distinct from the effect of IFNG-STAT1-IRF1 polarised cytotoxic responses. The latter represents the predominant immune response pattern separating cell of origin unclassifiable (Type-III) DLBCL from either ABC or GCB DLBCL subsets, and is associated with a trend toward positive outcome. Conclusion Comparative gene expression network analysis identifies common immune response signatures shared between DLBCL and other cancer types. Gene expression clusters linked to CD163 macrophage responses and IFNG-STAT1-IRF1 polarised cytotoxic responses are common patterns with apparent divergent outcome association. Disclosures Davies: CTI: Honoraria; GIlead: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Bayer: Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; GSK: Research Funding; Pfizer: Honoraria; Celgene: Honoraria, Research Funding. Jack:Jannsen: Research Funding.


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