Novel modelling of clustering for enhanced classification performance on gene expression data

Gene expression data is popularized for its capability to disclose various disease conditions. However, the conventional procedure to extract gene expression data itself incorporates various artifacts that offer challenges in diagnosis a complex disease indication and classification like cancer. Review of existing research approaches indicates that classification approaches are few to proven to be standard with respect to higher accuracy and applicable to gene expression data apart from unaddresed problems of computational complexity. Therefore, the proposed manuscript introduces a novel and simplified model capable using Graph Fourier Transform, Eigen Value and vector for offering better classification performance considering case study of microarray database, which is one typical example of gene expression data. The study outcome shows that proposed system offers comparatively better accuracy and reduced computational complexity with the existing clustering approaches

Tumor classification and marker gene prediction by feature selection and fuzzy c-means clustering using microarray data

BACKGROUND: Using DNA microarrays, we have developed two novel models for tumor classification and target gene prediction. First, gene expression profiles are summarized by optimally selected Self-Organizing Maps (SOMs), followed by tumor sample classification by Fuzzy C-means clustering. Then, the prediction of marker genes is accomplished by either manual feature selection (visualizing the weighted/mean SOM component plane) or automatic feature selection (by pair-wise Fisher's linear discriminant). RESULTS: The proposed models were tested on four published datasets: (1) Leukemia (2) Colon cancer (3) Brain tumors and (4) NCI cancer cell lines. The models gave class prediction with markedly reduced error rates compared to other class prediction approaches, and the importance of feature selection on microarray data analysis was also emphasized. CONCLUSIONS: Our models identify marker genes with predictive potential, often better than other available methods in the literature. The models are potentially useful for medical diagnostics and may reveal some insights into cancer classification. Additionally, we illustrated two limitations in tumor classification from microarray data related to the biology underlying the data, in terms of (1) the class size of data, and (2) the internal structure of classes. These limitations are not specific for the classification models used

Gene set based ensemble methods for cancer classification

Diagnosis of cancer very often depends on conclusions drawn after both clinical and microscopic examinations of tissues to study the manifestation of the disease in order to place tumors in known categories. One factor which determines the categorization of cancer is the tissue from which the tumor originates. Information gathered from clinical exams may be partial or not completely predictive of a specific category of cancer. Further complicating the problem of categorizing various tumors is that the histological classification of the cancer tissue and description of its course of development may be atypical. Gene expression data gleaned from micro-array analysis provides tremendous promise for more accurate cancer diagnosis. One hurdle in the classification of tumors based on gene expression data is that the data space is ultra-dimensional with relatively few points; that is, there are a small number of examples with a large number of genes. A second hurdle is expression bias caused by the correlation of genes. Analysis of subsets of genes, known as gene set analysis, provides a mechanism by which groups of differentially expressed genes can be identified. We propose an ensemble of classifiers whose base classifiers are ℓ1-regularized logistic regression models with restriction of the feature space to biologically relevant genes. Some researchers have already explored the use of ensemble classifiers to classify cancer but the effect of the underlying base classifiers in conjunction with biologically-derived gene sets on cancer classification has not been explored

A unified framework for finding differentially expressed genes from microarray experiments

<p>Abstract</p> <p>Background</p> <p>This paper presents a unified framework for finding differentially expressed genes (DEGs) from the microarray data. The proposed framework has three interrelated modules: (i) gene ranking, ii) significance analysis of genes and (iii) validation. The first module uses two gene selection algorithms, namely, a) two-way clustering and b) combined adaptive ranking to rank the genes. The second module converts the gene ranks into p-values using an R-test and fuses the two sets of p-values using the Fisher's omnibus criterion. The DEGs are selected using the FDR analysis. The third module performs three fold validations of the obtained DEGs. The robustness of the proposed unified framework in gene selection is first illustrated using false discovery rate analysis. In addition, the clustering-based validation of the DEGs is performed by employing an adaptive subspace-based clustering algorithm on the training and the test datasets. Finally, a projection-based visualization is performed to validate the DEGs obtained using the unified framework.</p> <p>Results</p> <p>The performance of the unified framework is compared with well-known ranking algorithms such as t-statistics, Significance Analysis of Microarrays (SAM), Adaptive Ranking, Combined Adaptive Ranking and Two-way Clustering. The performance curves obtained using 50 simulated microarray datasets each following two different distributions indicate the superiority of the unified framework over the other reported algorithms. Further analyses on 3 real cancer datasets and 3 Parkinson's datasets show the similar improvement in performance. First, a 3 fold validation process is provided for the two-sample cancer datasets. In addition, the analysis on 3 sets of Parkinson's data is performed to demonstrate the scalability of the proposed method to multi-sample microarray datasets.</p> <p>Conclusion</p> <p>This paper presents a unified framework for the robust selection of genes from the two-sample as well as multi-sample microarray experiments. Two different ranking methods used in module 1 bring diversity in the selection of genes. The conversion of ranks to p-values, the fusion of p-values and FDR analysis aid in the identification of significant genes which cannot be judged based on gene ranking alone. The 3 fold validation, namely, robustness in selection of genes using FDR analysis, clustering, and visualization demonstrate the relevance of the DEGs. Empirical analyses on 50 artificial datasets and 6 real microarray datasets illustrate the efficacy of the proposed approach. The analyses on 3 cancer datasets demonstrate the utility of the proposed approach on microarray datasets with two classes of samples. The scalability of the proposed unified approach to multi-sample (more than two sample classes) microarray datasets is addressed using three sets of Parkinson's Data. Empirical analyses show that the unified framework outperformed other gene selection methods in selecting differentially expressed genes from microarray data.</p

Unsupervised Discovery and Representation of Subspace Trends in Massive Biomedical Datasets

The goal of this dissertation is to develop unsupervised algorithms for discovering previously unknown subspace trends in massive multivariate biomedical data sets without the benefit of prior information. A subspace trend is a sustained pattern of gradual/progressive changes within an unknown subset of feature dimensions. A fundamental challenge to subspace trend discovery is the presence of irrelevant data dimensions, noise, outliers, and confusion from multiple subspace trends driven by independent factors that are mixed in with each other. These factors can obscure the trends in traditional dimension reduction and projection based data visualizations. To overcome these limitations, we propose a novel graph-theoretic neighborhood similarity measure for sensing concordant progressive changes across data dimensions. Using this measure, we present an unsupervised algorithm for trend-relevant feature selection and visualization. Additionally, we propose to use an efficient online density-based representation to make the algorithm scalable for massive datasets. The representation not only assists in trend discovery, but also in cluster detection including rare populations. Our method has been successfully applied to diverse synthetic and real-world biomedical datasets, such as gene expression microarray and arbor morphology of neurons and microglia in brain tissue. Derived representations revealed biologically meaningful hidden subspace trend(s) that were obscured by irrelevant features and noise. Although our applications are mostly from the biomedical domain, the proposed algorithm is broadly applicable to exploratory analysis of high-dimensional data including visualization, hypothesis generation, knowledge discovery, and prediction in diverse other applications.Electrical and Computer Engineering, Department o

Information visualization for DNA microarray data analysis: A critical review

Graphical representation may provide effective means of making sense of the complexity and sheer volume of data produced by DNA microarray experiments that monitor the expression patterns of thousands of genes simultaneously. The ability to use ldquoabstractrdquo graphical representation to draw attention to areas of interest, and more in-depth visualizations to answer focused questions, would enable biologists to move from a large amount of data to particular records they are interested in, and therefore, gain deeper insights in understanding the microarray experiment results. This paper starts by providing some background knowledge of microarray experiments, and then, explains how graphical representation can be applied in general to this problem domain, followed by exploring the role of visualization in gene expression data analysis. Having set the problem scene, the paper then examines various multivariate data visualization techniques that have been applied to microarray data analysis. These techniques are critically reviewed so that the strengths and weaknesses of each technique can be tabulated. Finally, several key problem areas as well as possible solutions to them are discussed as being a source for future work

Effective Linear-Time Feature Selection

The classification learning task requires selection of a subset of features to represent patterns to be classified. This is because the performance of the classifier and the cost of classification are sensitive to the choice of the features used to construct the classifier. Exhaustive search is impractical since it searches every possible combination of features. The runtime of heuristic and random searches are better but the problem still persists when dealing with high-dimensional datasets. We investigate a heuristic, forward, wrapper-based approach, called Linear Sequential Selection, which limits the search space at each iteration of the feature selection process. We introduce randomization in the search space. The algorithm is called Randomized Linear Sequential Selection. Our experiments demonstrate that both methods are faster, find smaller subsets and can even increase the classification accuracy. We also explore the idea of ensemble learning. We have proposed two ensemble creation methods, Feature Selection Ensemble and Random Feature Ensemble. Both methods apply a feature selection algorithm to create individual classifiers of the ensemble. Our experiments have shown that both methods work well with high-dimensional data

Hierarchical maximum likelihood clustering approach

Objective: In this work, we focused on developing a clustering approach for biological data. In many biological analyses, such as multi-omics data analysis and genome-wide association studies (GWAS) analysis, it is crucial to find groups of data belonging to subtypes of diseases or tumors. Methods: Conventionally, the k-means clustering algorithm is overwhelmingly applied in many areas including biological sciences. There are, however, several alternative clustering algorithms that can be applied, including support vector clustering. In this paper, taking into consideration the nature of biological data, we propose a maximum likelihood clustering scheme based on a hierarchical framework. Results: This method can perform clustering even when the data belonging to different groups overlap. It can also perform clustering when the number of samples is lower than the data dimensionality. Conclusion: The proposed scheme is free from selecting initial settings to begin the search process. In addition, it does not require the computation of the first and second derivative of likelihood functions, as is required by many other maximum likelihood based methods. Significance: This algorithm uses distribution and centroid information to cluster a sample and was applied to biological data. A Matlab implementation of this method can be downloaded from the web-link http://www.riken.jp/en/research/labs/ims/med_sci_math/