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Journal ArticleDOI

μHEM for identification of differentially expressed miRNAs using hypercuboid equivalence partition matrix

04 Sep 2013-BMC Bioinformatics (BioMed Central)-Vol. 14, Iss: 1, pp 266-266

TL;DR: The results on several microarray data sets demonstrate that the proposed method can bring a remarkable improvement on miRNA selection problem and is a potentially useful tool for exploration of miRNA expression data and identification of differentially expressed miRNAs worth further investigation.

AbstractThe miRNAs, a class of short approximately 22‐nucleotide non‐coding RNAs, often act post‐transcriptionally to inhibit mRNA expression. In effect, they control gene expression by targeting mRNA. They also help in carrying out normal functioning of a cell as they play an important role in various cellular processes. However, dysregulation of miRNAs is found to be a major cause of a disease. It has been demonstrated that miRNA expression is altered in many human cancers, suggesting that they may play an important role as disease biomarkers. Multiple reports have also noted the utility of miRNAs for the diagnosis of cancer. Among the large number of miRNAs present in a microarray data, a modest number might be sufficient to classify human cancers. Hence, the identification of differentially expressed miRNAs is an important problem particularly for the data sets with large number of miRNAs and small number of samples. In this regard, a new miRNA selection algorithm, called μHEM, is presented based on rough hypercuboid approach. It selects a set of miRNAs from a microarray data by maximizing both relevance and significance of the selected miRNAs. The degree of dependency of sample categories on miRNAs is defined, based on the concept of hypercuboid equivalence partition matrix, to measure both relevance and significance of miRNAs. The effectiveness of the new approach is demonstrated on six publicly available miRNA expression data sets using support vector machine. The.632+ bootstrap error estimate is used to minimize the variability and biasedness of the derived results. An important finding is that the μHEM algorithm achieves lowest B.632+ error rate of support vector machine with a reduced set of differentially expressed miRNAs on four expression data sets compare to some existing machine learning and statistical methods, while for other two data sets, the error rate of the μHEM algorithm is comparable with the existing techniques. The results on several microarray data sets demonstrate that the proposed method can bring a remarkable improvement on miRNA selection problem. The method is a potentially useful tool for exploration of miRNA expression data and identification of differentially expressed miRNAs worth further investigation.

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Citations
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Journal ArticleDOI
TL;DR: The formulation enables the proposed method to extract required number of correlated features sequentially with lesser computational cost as compared to existing methods, and provides an efficient way to find optimum regularization parameters employed in CCA.
Abstract: One of the main problems associated with high dimensional multimodal real life data sets is how to extract relevant and significant features. In this regard, a fast and robust feature extraction algorithm, termed as FaRoC, is proposed, integrating judiciously the merits of canonical correlation analysis (CCA) and rough sets. The proposed method extracts new features sequentially from two multidimensional data sets by maximizing their relevance with respect to class label and significance with respect to already-extracted features. To generate canonical variables sequentially, an analytical formulation is introduced to establish the relation between regularization parameters and CCA. The formulation enables the proposed method to extract required number of correlated features sequentially with lesser computational cost as compared to existing methods. To compute both significance and relevance measures of a feature, the concept of hypercuboid equivalence partition matrix of rough hypercuboid approach is used. It also provides an efficient way to find optimum regularization parameters employed in CCA. The efficacy of the proposed FaRoC algorithm, along with a comparison with other existing methods, is extensively established on several real life data sets.

16 citations


Cites methods from "μHEM for identification of differen..."

  • ...It has been applied successfully for analyzing omics data [34], [45], [46]....

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Journal ArticleDOI
TL;DR: The proposed prediction model provides an effective tool for DLB classification and predicted candidate target genes from the miRNAs, including 6 functional genes included in the DHA signaling pathway associated with DLB pathology.
Abstract: Dementia with Lewy bodies (DLB) is the second most common subtype of neurodegenerative dementia in humans following Alzheimer’s disease (AD). Present clinical diagnosis of DLB has high specificity and low sensitivity and finding potential biomarkers of prodromal DLB is still challenging. MicroRNAs (miRNAs) have recently received a lot of attention as a source of novel biomarkers. In this study, using serum miRNA expression of 478 Japanese individuals, we investigated potential miRNA biomarkers and constructed an optimal risk prediction model based on several machine learning methods: penalized regression, random forest, support vector machine, and gradient boosting decision tree. The final risk prediction model, constructed via a gradient boosting decision tree using 180 miRNAs and two clinical features, achieved an accuracy of 0.829 on an independent test set. We further predicted candidate target genes from the miRNAs. Gene set enrichment analysis of the miRNA target genes revealed 6 functional genes included in the DHA signaling pathway associated with DLB pathology. Two of them were further supported by gene-based association studies using a large number of single nucleotide polymorphism markers (BCL2L1: P = 0.012, PIK3R2: P = 0.021). Our proposed prediction model provides an effective tool for DLB classification. Also, a gene-based association test of rare variants revealed that BCL2L1 and PIK3R2 were statistically significantly associated with DLB.

15 citations


Cites methods from "μHEM for identification of differen..."

  • ...This final risk prediction model using μHEM algorithm achieved an accuracy of 0.803 on an independent test set when pre-selecting the top-ranked 330 miRNAs and three clinical features....

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  • ...Paul S, Maji P. muHEM for identification of differentially expressed miRNAs using hypercuboid equivalence partition matrix....

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  • ...We also constructed a GBDT risk prediction model using another feature selection algorithm, μHEM [23], publicly available at http://www....

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  • ...We also constructed a GBDT risk prediction model using another feature selection algorithm, μHEM [23], publicly available at http://www.isical.ac.in/~bibl/results/ mihem/mihem.html, and investigated whether this feature selection methodology can further improve the predictive ability of our model....

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  • ...Hyperparameter values in the final GBDT model when using μHEM algorithm....

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Journal ArticleDOI
TL;DR: Results indicate that the integrated method presented is quite promising and may become a useful tool for identifying disease genes.
Abstract: One of the most important and challenging problems in functional genomics is how to select the disease genes. In this regard, the paper presents a new computational method to identify disease genes. It judiciously integrates the information of gene expression profiles and shortest path analysis of protein---protein interaction networks. While the $$f$$f-information based maximum relevance-maximum significance framework is used to select differentially expressed genes as disease genes using gene expression profiles, the functional protein association network is used to study the mechanism of diseases. An important finding is that some $$f$$f-information measures are shown to be effective for selecting relevant and significant genes from microarray data. Extensive experimental study on colorectal cancer establishes the fact that the genes identified by the integrated method have more colorectal cancer genes than the genes identified from the gene expression profiles alone, irrespective of any gene selection algorithm. Also, these genes have greater functional similarity with the reported colorectal cancer genes than the genes identified from the gene expression profiles alone. The enrichment analysis of the obtained genes reveals to be associated with some of the important KEGG pathways. All these results indicate that the integrated method is quite promising and may become a useful tool for identifying disease genes.

12 citations


Cites methods from "μHEM for identification of differen..."

  • ...The f -MRMS algorithm judiciously integrates the merits of maximum relevancemaximum significance (MRMS) criterion (Maji and Paul 2011; Paul and Maji 2013a, b) and f -information measures....

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Journal ArticleDOI
TL;DR: A novel supervised regularized canonical correlation analysis, termed as CuRSaR, to extract relevant and significant features from multimodal high dimensional omics datasets by maximizing the relevance of extracted features with respect to sample categories and significance among them.
Abstract: Objective: This paper presents a novel supervised regularized canonical correlation analysis, termed as CuRSaR, to extract relevant and significant features from multimodal high dimensional omics datasets. Methods: The proposed method extracts a new set of features from two multidimensional datasets by maximizing the relevance of extracted features with respect to sample categories and significance among them. It integrates judiciously the merits of regularized canonical correlation analysis (RCCA) and rough hypercuboid approach. An analytical formulation, based on spectral decomposition, is introduced to establish the relation between canonical correlation analysis (CCA) and RCCA. The concept of hypercuboid equivalence partition matrix of rough hypercuboid is used to compute both relevance and significance of a feature. Significance: The analytical formulation makes the computational complexity of the proposed algorithm significantly lower than existing methods. The equivalence partition matrix offers an efficient way to find optimum regularization parameters employed in CCA. Results: The superiority of the proposed algorithm over other existing methods, in terms of computational complexity and classification accuracy, is established extensively on real life data.

9 citations


Cites methods from "μHEM for identification of differen..."

  • ...It has been applied successfully to feature selection and clustering [27] as well as to omics data analysis [26]–[30]....

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Journal ArticleDOI
TL;DR: This study presents an application of the RH-SAC algorithm on miRNA and mRNA expression data for identification of potential miRNA-mRNA modules and identified novel miRNA/mRNA interactions in colorectal cancer.
Abstract: Differences in the expression profiles of miRNAs and mRNAs have been reported in colorectal cancer. Nevertheless, information on important miRNA-mRNA regulatory modules in colorectal cancer is still lacking. In this regard, this study presents an application of the RH-SAC algorithm on miRNA and mRNA expression data for identification of potential miRNA-mRNA modules. First, a set of miRNA rules was generated using the RH-SAC algorithm. The mRNA targets of the selected miRNAs were identified using the miRTarBase database. Next, the expression values of target mRNAs were used to generate mRNA rules using the RH-SAC. Then all miRNA-mRNA rules have been integrated for generating networks. The RH-SAC algorithm unlike other existing methods selects a group of co-expressed miRNAs and mRNAs that are also differentially expressed. In total 17 miRNAs and 141 mRNAs were selected. The enrichment analysis of selected mRNAs revealed that our method selected mRNAs that are significantly associated with colorectal cancer. We identified novel miRNA/mRNA interactions in colorectal cancer. Through experiment, we could confirm that one of our discovered miRNAs, hsa-miR-93-5p, was significantly up-regulated in 75.8% CRC in comparison to their corresponding non-tumor samples. It could have the potential to examine colorectal cancer subtype specific unique miRNA/mRNA interactions.

8 citations


References
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Book
Vladimir Vapnik1
01 Jan 1995
TL;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?
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38,164 citations


"μHEM for identification of differen..." refers methods in this paper

  • ...The μHEM algorithm attains lowest B.632+ error rate of the SVM classifier for GSE17681, GSE21036, GSE24709, and GSE31408 data sets, while boosting achieves it only on GSE17846 and GSE28700 data sets....

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  • ...The source code of the SVM has been downloaded from Library for Support Vector Machines (www.csie.ntu.edu.tw/~cjlin/ libsvm/)....

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  • ...0 0.1 0.2 0.3 0.4 0.5 0.6 0 5 10 15 20 25 30 35 40 45 50 E rr or R at e Number of Selected miRNAs GSE17681 AE B1 γ B.632+ 0 0.1 0.2 0.3 0.4 0.5 0.6 0 5 10 15 20 25 30 35 40 45 50 E rr or R at e Number of Selected miRNAs GSE17846 AE B1 γ B.632+ Figure 7 Different error rates of the proposed algorithm on GSE17681 and GSE17846 data sets obtained using the SVM averaged over 50 random splits. irrespective of the algorithms and data sets used....

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  • ...To compute different types of error rates obtained using the SVM, bootstrap approach is performed on each miRNA expression data set....

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Journal ArticleDOI
TL;DR: A new method for estimation in linear models called the lasso, which minimizes the residual sum of squares subject to the sum of the absolute value of the coefficients being less than a constant, is proposed.
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"μHEM for identification of differen..." refers methods in this paper

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TL;DR: A complete guide to the C4.5 system as implemented in C for the UNIX environment, which starts from simple core learning methods and shows how they can be elaborated and extended to deal with typical problems such as missing data and over hitting.
Abstract: From the Publisher: Classifier systems play a major role in machine learning and knowledge-based systems, and Ross Quinlan's work on ID3 and C4.5 is widely acknowledged to have made some of the most significant contributions to their development. This book is a complete guide to the C4.5 system as implemented in C for the UNIX environment. It contains a comprehensive guide to the system's use , the source code (about 8,800 lines), and implementation notes. The source code and sample datasets are also available on a 3.5-inch floppy diskette for a Sun workstation. C4.5 starts with large sets of cases belonging to known classes. The cases, described by any mixture of nominal and numeric properties, are scrutinized for patterns that allow the classes to be reliably discriminated. These patterns are then expressed as models, in the form of decision trees or sets of if-then rules, that can be used to classify new cases, with emphasis on making the models understandable as well as accurate. The system has been applied successfully to tasks involving tens of thousands of cases described by hundreds of properties. The book starts from simple core learning methods and shows how they can be elaborated and extended to deal with typical problems such as missing data and over hitting. Advantages and disadvantages of the C4.5 approach are discussed and illustrated with several case studies. This book and software should be of interest to developers of classification-based intelligent systems and to students in machine learning and expert systems courses.

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15 Oct 1999-Science
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.

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Journal ArticleDOI
09 Jun 2005-Nature
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
Abstract: Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.

8,996 citations


"μHEM for identification of differen..." refers background in this paper

  • ...Multiple reports have noted the utility of miRNAs for the diagnosis of cancer and other diseases [1]....

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  • ...[1], unlike with mRNAs, a modest number of miRNAs might be sufficient to classify human cancers....

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  • ...Unlike with mRNAs, a modest number of miRNAs might be sufficient to classify human cancers [1]....

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  • ...Different statistical tests are also employed to identify differentially expressed miRNAs [1,4-8,17-20]....

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