μHEM for identification of differentially expressed miRNAs using hypercuboid equivalence partition matrix
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.
Abstract: The 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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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.
24 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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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.
23 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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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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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.
9 citations
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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References
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TL;DR: In this review, the mechanisms to alter microRNA expression and their relation to cancer will be addressed, and the potential application of microRNAs in clinical settings will also be highlighted.
Abstract: MicroRNAs are small noncoding RNAs that function to control gene expression. These small RNAs have been shown to contribute to the control of cell growth, differentiation and apoptosis, important features related to cancer development and progression. In fact, recent studies have shown the utility of microRNAs as cancer-related biomarkers. This is due to the finding that microRNAs display altered expression profiles in cancers versus normal tissue. In addition, microRNAs have been associated with cancer progression. In this review, the mechanisms to alter microRNA expression and their relation to cancer will be addressed. Moreover, the potential application of microRNAs in clinical settings will also be highlighted. Finally, the challenges regarding the translation of research involving microRNAs to the clinical realm will be discussed.
111 citations
01 Jun 2010
TL;DR: The concept of the fuzzy equivalence partition matrix is presented to approximate the true marginal and joint distributions of continuous gene expression values and is shown to be effective for selecting relevant and nonredundant continuous-valued genes from microarray data.
Abstract: Several information measures such as entropy, mutual information, and f-information have been shown to be successful for selecting a set of relevant and nonredundant genes from a high-dimensional microarray data set. However, for continuous gene expression values, it is very difficult to find the true density functions and to perform the integrations required to compute different information measures. In this regard, the concept of the fuzzy equivalence partition matrix is presented to approximate the true marginal and joint distributions of continuous gene expression values. The fuzzy equivalence partition matrix is based on the theory of fuzzy-rough sets, where each row of the matrix represents a fuzzy equivalence partition that can automatically be derived from the given expression values. The performance of the proposed approach is compared with that of existing approaches using the class separability index and the predictive accuracy of the support vector machine. An important finding, however, is that the proposed approach is shown to be effective for selecting relevant and nonredundant continuous-valued genes from microarray data.
96 citations
"μHEM for identification of differen..." refers methods in this paper
...The theory of rough sets has also been successfully applied to microarray data analysis in [9,24-35]....
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TL;DR: An efficient method is proposed to select initial prototypes of different gene clusters, which enables the proposed c-means algorithm to converge to an optimum or near optimum solutions and helps to discover coexpressed gene clusters.
Abstract: Gene expression data clustering is one of the important tasks of functional genomics as it provides a powerful tool for studying functional relationships of genes in a biological process. Identifying coexpressed groups of genes represents the basic challenge in gene clustering problem. In this regard, a gene clustering algorithm, termed as robust rough-fuzzy $(c)$-means, is proposed judiciously integrating the merits of rough sets and fuzzy sets. While the concept of lower and upper approximations of rough sets deals with uncertainty, vagueness, and incompleteness in cluster definition, the integration of probabilistic and possibilistic memberships of fuzzy sets enables efficient handling of overlapping partitions in noisy environment. The concept of possibilistic lower bound and probabilistic boundary of a cluster, introduced in robust rough-fuzzy $(c)$-means, enables efficient selection of gene clusters. An efficient method is proposed to select initial prototypes of different gene clusters, which enables the proposed $(c)$-means algorithm to converge to an optimum or near optimum solutions and helps to discover coexpressed gene clusters. The effectiveness of the algorithm, along with a comparison with other algorithms, is demonstrated both qualitatively and quantitatively on 14 yeast microarray data sets.
95 citations
"μHEM for identification of differen..." refers methods in this paper
...The theory of rough sets has also been successfully applied to microarray data analysis in [9,24-35]....
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01 Feb 2011
TL;DR: The proposed FRSAC algorithm is based on measuring the similarity between genes using the new quantitative measure, whereby redundancy among the genes is removed and the clusters are refined incrementally based on sample categories.
Abstract: One of the major tasks with gene expression data is to find groups of coregulated genes whose collective expression is strongly associated with sample categories. In this regard, a new clustering algorithm, termed as fuzzy-rough supervised attribute clustering (FRSAC), is proposed to find such groups of genes. The proposed algorithm is based on the theory of fuzzy-rough sets, which directly incorporates the information of sample categories into the gene clustering process. A new quantitative measure is introduced based on fuzzy-rough sets that incorporates the information of sample categories to measure the similarity among genes. The proposed algorithm is based on measuring the similarity between genes using the new quantitative measure, whereby redundancy among the genes is removed. The clusters are refined incrementally based on sample categories. The effectiveness of the proposed FRSAC algorithm, along with a comparison with existing supervised and unsupervised gene selection and clustering algorithms, is demonstrated on six cancer and two arthritis data sets based on the class separability index and predictive accuracy of the naive Bayes' classifier, the K-nearest neighbor rule, and the support vector machine.
86 citations
"μHEM for identification of differen..." refers methods in this paper
...The theory of rough sets has also been successfully applied to microarray data analysis in [9,24-35]....
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TL;DR: The present data suggest that miR-148a could be a potential prognostic biomarker of gastric cancer and function as a tumor suppressor through repressing the activity of its regulated PIN.
Abstract: Background
MicroRNAs (miRNAs) are a class of endogenous, small and highly conserved noncoding RNAs that control gene expression either by degradation of target mRNAs or by inhibition of protein translation. They play important roles in cancer progression. A single miRNA can provoke a chain reaction and further affect protein interaction network (PIN). Therefore, we developed a novel integrative approach to identify the functional roles and the regulated PIN of oncomirs.
84 citations
"μHEM for identification of differen..." refers background in this paper
...The samples are grouped into 2 classes [41]....
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