Network-based support vector machine for classification of microarray samples
TL;DR: A network-based support vector machine is proposed for binary classification problems by constructing a penalty term from the F∞-norm being applied to pairwise gene neighbors with the hope to improve predictive performance and gene selection.
Abstract: The importance of network-based approach to identifying biological markers for diagnostic classification and prognostic assessment in the context of microarray data has been increasingly recognized. To our knowledge, there have been few, if any, statistical tools that explicitly incorporate the prior information of gene networks into classifier building. The main idea of this paper is to take full advantage of the biological observation that neighboring genes in a network tend to function together in biological processes and to embed this information into a formal statistical framework. We propose a network-based support vector machine for binary classification problems by constructing a penalty term from the F∞-norm being applied to pairwise gene neighbors with the hope to improve predictive performance and gene selection. Simulation studies in both low- and high-dimensional data settings as well as two real microarray applications indicate that the proposed method is able to identify more clinically relevant genes while maintaining a sparse model with either similar or higher prediction accuracy compared with the standard and the L1 penalized support vector machines. The proposed network-based support vector machine has the potential to be a practically useful classification tool for microarrays and other high-dimensional data.
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TL;DR: The new concept of dynamical network biomarkers (DNBs) has been developed, which is different from traditional static approaches, and the DNB is able to distinguish a predisease state from normal and disease states by even a small number of samples, and therefore has great potential to achieve “real” early diagnosis of complex diseases.
Abstract: Many studies have been carried out for early diagnosis of complex diseases by finding accurate and robust biomarkers specific to respective diseases. In particular, recent rapid advance of high-throughput technologies provides unprecedented rich information to characterize various disease genotypes and phenotypes in a global and also dynamical manner, which significantly accelerates the study of biomarkers from both theoretical and clinical perspectives. Traditionally, molecular biomarkers that distinguish disease samples from normal samples are widely adopted in clinical practices due to their ease of data measurement. However, many of them suffer from low coverage and high false-positive rates or high false-negative rates, which seriously limit their further clinical applications. To overcome those difficulties, network biomarkers (or module biomarkers) attract much attention and also achieve better performance because a network (or subnetwork) is considered to be a more robust form to characterize diseases than individual molecules. But, both molecular biomarkers and network biomarkers mainly distinguish disease samples from normal samples, and they generally cannot ensure to identify predisease samples due to their static nature, thereby lacking ability to early diagnosis. Based on nonlinear dynamical theory and complex network theory, a new concept of dynamical network biomarkers (DNBs, or a dynamical network of biomarkers) has been developed, which is different from traditional static approaches, and the DNB is able to distinguish a predisease state from normal and disease states by even a small number of samples, and therefore has great potential to achieve "real" early diagnosis of complex diseases. In this paper, we comprehensively review the recent advances and developments on molecular biomarkers, network biomarkers, and DNBs in particular, focusing on the biomarkers for early diagnosis of complex diseases considering a small number of samples and high-throughput data (or big data). Detailed comparisons of various types of biomarkers as well as their applications are also discussed.
230 citations
TL;DR: A grouped penalty based on the Lγ‐norm that smoothes the regression coefficients of the predictors over the network is proposed that performs best in variable selection across all simulation set‐ups considered.
Abstract: We consider penalized linear regression, especially for “large p, small n” problems, for which the relationships among predictors are described a priori by a network. A class of motivating examples includes modeling a phenotype through gene expression profiles while accounting for coordinated functioning of genes in the form of biological pathways or networks. To incorporate the prior knowledge of the similar effect sizes of neighboring predictors in a network, we propose a grouped penalty based on the Lγ-norm that smoothes the regression coefficients of the predictors over the network. The main feature of the proposed method is its ability to automatically realize grouped variable selection and exploit grouping effects. We also discuss effects of the choices of the γ and some weights inside the Lγ-norm. Simulation studies demonstrate the superior finite sample performance of the proposed method as compared to Lasso, elastic net and a recently proposed network-based method. The new method performs best in variable selection across all simulation set-ups considered. For illustration, the method is applied to a microarray dataset to predict survival times for some glioblastoma patients using a gene expression dataset and a gene network compiled from some KEGG pathways.
127 citations
Cites background from "Network-based support vector machin..."
...…straightforward, at least in principle, to apply our proposed network-based penalty to generalized linear models (e.g., Zhu and Hastie, 2004) and other classification models (Zhu, Shen, and Pan, 2009), though more work, especially in developing fast and accurate computational algorithms, is needed....
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TL;DR: This study aims at developing a novel method utilizing particle swarm optimization combined with a decision tree as the classifier that outperforms other popular classifiers for all test datasets, and is compatible to SVM for certain specific datasets.
Abstract: In the application of microarray data, how to select a small number of informative genes from thousands of genes that may contribute to the occurrence of cancers is an important issue. Many researchers use various computational intelligence methods to analyzed gene expression data. To achieve efficient gene selection from thousands of candidate genes that can contribute in identifying cancers, this study aims at developing a novel method utilizing particle swarm optimization combined with a decision tree as the classifier. This study also compares the performance of our proposed method with other well-known benchmark classification methods (support vector machine, self-organizing map, back propagation neural network, C4.5 decision tree, Naive Bayes, CART decision tree, and artificial immune recognition system) and conducts experiments on 11 gene expression cancer datasets. Based on statistical analysis, our proposed method outperforms other popular classifiers for all test datasets, and is compatible to SVM for certain specific datasets. Further, the housekeeping genes with various expression patterns and tissue-specific genes are identified. These genes provide a high discrimination power on cancer classification.
123 citations
Cites methods from "Network-based support vector machin..."
...Genetic algorithms (GAs) [7] are generally used as the search engine for feature subset in the embedded method, while other classification methods, such as estimation of distribution algorithm (EDA) with SVM [8-13], K nearest neighbors/ genetic algorithms (KNN/GA) [14], genetic algorithmssupport vector machine (GA-SVM) [15] and so forth, are used to select feature subset....
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TL;DR: A newly developed classifier named Forest Deep Neural Network (fDNN), to integrate the deep neural network architecture with a supervised forest feature detector, which is able to learn sparse feature representations and feed the representations into a neural network to mitigate the overfitting problem.
Abstract: In predictive model development, gene expression data is associated with the unique challenge that the number of samples (n) is much smaller than the amount of features (p). This “n ≪ p” property has prevented classification of gene expression data from deep learning techniques, which have been proved powerful under “n > p” scenarios in other application fields, such as image classification. Further, the sparsity of effective features with unknown correlation structures in gene expression profiles brings more challenges for classification tasks. To tackle these problems, we propose a newly developed classifier named Forest Deep Neural Network (fDNN), to integrate the deep neural network architecture with a supervised forest feature detector. Using this built-in feature detector, the method is able to learn sparse feature representations and feed the representations into a neural network to mitigate the overfitting problem. Simulation experiments and real data analyses using two RNA-seq expression datasets are conducted to evaluate fDNN’s capability. The method is demonstrated a useful addition to current predictive models with better classification performance and more meaningful selected features compared to ordinary random forests and deep neural networks.
113 citations
TL;DR: It is concluded that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction.
102 citations
References
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01 Jan 1995TL;DR: Setting of the learning problem consistency of learning processes bounds on the rate of convergence ofLearning processes controlling the generalization ability of learning process constructing learning algorithms what is important in learning theory?
Abstract: Setting of the learning problem consistency of learning processes bounds on the rate of convergence of learning processes controlling the generalization ability of learning processes constructing learning algorithms what is important in learning theory?.
40,147 citations
TL;DR: High generalization ability of support-vector networks utilizing polynomial input transformations is demonstrated and the performance of the support- vector network is compared to various classical learning algorithms that all took part in a benchmark study of Optical Character Recognition.
Abstract: The support-vector network is a new learning machine for two-group classification problems. The machine conceptually implements the following idea: input vectors are non-linearly mapped to a very high-dimension feature space. In this feature space a linear decision surface is constructed. Special properties of the decision surface ensures high generalization ability of the learning machine. The idea behind the support-vector network was previously implemented for the restricted case where the training data can be separated without errors. We here extend this result to non-separable training data.
High generalization ability of support-vector networks utilizing polynomial input transformations is demonstrated. We also compare the performance of the support-vector network to various classical learning algorithms that all took part in a benchmark study of Optical Character Recognition.
37,861 citations
TL;DR: It is shown that the elastic net often outperforms the lasso, while enjoying a similar sparsity of representation, and an algorithm called LARS‐EN is proposed for computing elastic net regularization paths efficiently, much like algorithm LARS does for the lamba.
Abstract: Summary. We propose the elastic net, a new regularization and variable selection method. Real world data and a simulation study show that the elastic net often outperforms the lasso, while enjoying a similar sparsity of representation. In addition, the elastic net encourages a grouping effect, where strongly correlated predictors tend to be in or out of the model together.The elastic net is particularly useful when the number of predictors (p) is much bigger than the number of observations (n). By contrast, the lasso is not a very satisfactory variable selection method in the
16,538 citations
"Network-based support vector machin..." refers background in this paper
...Third, the penalty term, under certain conditions, tends to encourage a grouping effect, where highly correlated predictors tend to have similar coefficient estimates [17-20]....
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TL;DR: Chapter 11 includes more case studies in other areas, ranging from manufacturing to marketing research, and a detailed comparison with other diagnostic tools, such as logistic regression and tree-based methods.
Abstract: Chapter 11 includes more case studies in other areas, ranging from manufacturing to marketing research. Chapter 12 concludes the book with some commentary about the scienti c contributions of MTS. The Taguchi method for design of experiment has generated considerable controversy in the statistical community over the past few decades. The MTS/MTGS method seems to lead another source of discussions on the methodology it advocates (Montgomery 2003). As pointed out by Woodall et al. (2003), the MTS/MTGS methods are considered ad hoc in the sense that they have not been developed using any underlying statistical theory. Because the “normal” and “abnormal” groups form the basis of the theory, some sampling restrictions are fundamental to the applications. First, it is essential that the “normal” sample be uniform, unbiased, and/or complete so that a reliable measurement scale is obtained. Second, the selection of “abnormal” samples is crucial to the success of dimensionality reduction when OAs are used. For example, if each abnormal item is really unique in the medical example, then it is unclear how the statistical distance MD can be guaranteed to give a consistent diagnosis measure of severity on a continuous scale when the larger-the-better type S/N ratio is used. Multivariate diagnosis is not new to Technometrics readers and is now becoming increasingly more popular in statistical analysis and data mining for knowledge discovery. As a promising alternative that assumes no underlying data model, The Mahalanobis–Taguchi Strategy does not provide suf cient evidence of gains achieved by using the proposed method over existing tools. Readers may be very interested in a detailed comparison with other diagnostic tools, such as logistic regression and tree-based methods. Overall, although the idea of MTS/MTGS is intriguing, this book would be more valuable had it been written in a rigorous fashion as a technical reference. There is some lack of precision even in several mathematical notations. Perhaps a follow-up with additional theoretical justi cation and careful case studies would answer some of the lingering questions.
11,507 citations