WERFE: A Gene Selection Algorithm Based on Recursive Feature Elimination and Ensemble Strategy.
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ABSTRACT:
SUBMITTER: Chen Q
PROVIDER: S-EPMC7270206 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Project description:BackgroundClassification studies using gene expression datasets are usually based on small numbers of samples and tens of thousands of genes. The selection of those genes that are important for distinguishing the different sample classes being compared, poses a challenging problem in high dimensional data analysis. We describe a new procedure for selecting significant genes as recursive cluster elimination (RCE) rather than recursive feature elimination (RFE). We have tested this algorithm on six datasets and compared its performance with that of two related classification procedures with RFE.ResultsWe have developed a novel method for selecting significant genes in comparative gene expression studies. This method, which we refer to as SVM-RCE, combines K-means, a clustering method, to identify correlated gene clusters, and Support Vector Machines (SVMs), a supervised machine learning classification method, to identify and score (rank) those gene clusters for the purpose of classification. K-means is used initially to group genes into clusters. Recursive cluster elimination (RCE) is then applied to iteratively remove those clusters of genes that contribute the least to the classification performance. SVM-RCE identifies the clusters of correlated genes that are most significantly differentially expressed between the sample classes. Utilization of gene clusters, rather than individual genes, enhances the supervised classification accuracy of the same data as compared to the accuracy when either SVM or Penalized Discriminant Analysis (PDA) with recursive feature elimination (SVM-RFE and PDA-RFE) are used to remove genes based on their individual discriminant weights.ConclusionSVM-RCE provides improved classification accuracy with complex microarray data sets when it is compared to the classification accuracy of the same datasets using either SVM-RFE or PDA-RFE. SVM-RCE identifies clusters of correlated genes that when considered together provide greater insight into the structure of the microarray data. Clustering genes for classification appears to result in some concomitant clustering of samples into subgroups. Our present implementation of SVM-RCE groups genes using the correlation metric. The success of the SVM-RCE method in classification suggests that gene interaction networks or other biologically relevant metrics that group genes based on functional parameters might also be useful.
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Project description:There is great interest in methods to improve human insight into trained non-linear models. Leading approaches include producing a ranking of the most relevant features, a non-trivial task for non-linear models. We show theoretically and empirically the benefit of a novel version of recursive feature elimination (RFE) as often used with SVMs; the key idea is a simple twist on the kinds of sensitivity testing employed in computational learning theory with membership queries (e.g., [1]). With membership queries, one can check whether changing the value of a feature in an example changes the label. In the real-world, we usually cannot get answers to such queries, so our approach instead makes these queries to a trained (imperfect) non-linear model. Because SVMs are widely used in bioinformatics, our empirical results use a real-world cancer genomics problem; because ground truth is not known for this task, we discuss the potential insights provided. We also evaluate on synthetic data where ground truth is known.
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Project description:MotivationAdvances in technology have generated larger omics datasets with potential applications for machine learning. In many datasets, however, cost and limited sample availability result in an excessively higher number of features as compared to observations. Moreover, biological processes are associated with networks of core and peripheral genes, while traditional feature selection approaches capture only core genes.ResultsTo overcome these limitations, we present dRFEtools that implements dynamic recursive feature elimination (RFE), reducing computational time with high accuracy compared to standard RFE, expanding dynamic RFE to regression algorithms, and outputting the subsets of features that hold predictive power with and without peripheral features. dRFEtools integrates with scikit-learn (the popular Python machine learning platform) and thus provides new opportunities for dynamic RFE in large-scale omics data while enhancing its interpretability.Availability and implementationdRFEtools is freely available on PyPI at https://pypi.org/project/drfetools/ or on GitHub https://github.com/LieberInstitute/dRFEtools, implemented in Python 3, and supported on Linux, Windows, and Mac OS.
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Project description:Background: Open spina bifida (myelomeningocele) is the result of the failure of spinal cord closing completely and is the second most common and severe birth defect. Open neural tube defects are multifactorial, and the exact molecular mechanism of the pathogenesis is not clear due to disease complexity for which prenatal treatment options remain limited worldwide. Artificial intelligence techniques like machine learning tools have been increasingly used in precision diagnosis. Objective: The primary objective of this study is to identify key genes for open neural tube defects using a machine learning approach that provides additional information about myelomeningocele in order to obtain a more accurate diagnosis. Materials and Methods: Our study reports differential gene expression analysis from multiple datasets (GSE4182 and GSE101141) of amniotic fluid samples with open neural tube defects. The sample outliers in the datasets were detected using principal component analysis (PCA). We report a combination of the differential gene expression analysis with recursive feature elimination (RFE), a machine learning approach to get 4 key genes for open neural tube defects. The features selected were validated using five binary classifiers for diseased and healthy samples: Logistic Regression (LR), Decision tree classifier (DT), Support Vector Machine (SVM), Random Forest classifier (RF), and K-nearest neighbour (KNN) with 5-fold cross-validation. Results: Growth Associated Protein 43 (GAP43), Glial fibrillary acidic protein (GFAP), Repetin (RPTN), and CD44 are the important genes identified in the study. These genes are known to be involved in axon growth, astrocyte differentiation in the central nervous system, post-traumatic brain repair, neuroinflammation, and inflammation-linked neuronal injuries. These key genes represent a promising tool for further studies in the diagnosis and early detection of open neural tube defects. Conclusion: These key biomarkers help in the diagnosis and early detection of open neural tube defects, thus evaluating the progress and seriousness in diseases condition. This study strengthens previous literature sources of confirming these biomarkers linked with open NTD's. Thus, among other prenatal treatment options present until now, these biomarkers help in the early detection of open neural tube defects, which provides success in both treatment and prevention of these defects in the advanced stage.
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Project description:The aim of the present study was to identify risk genes in myocardial infarction. Microarray data GSE34198, containing data from the peripheral blood of 49 myocardial infarction samples and 48 corresponding control samples, were downloaded from the Gene Expression Omnibus database to screen the differentially expressed genes (DEGs). The DEGs were used to construct a protein‑protein interaction (PPI) network of patient samples, from which the feature genes were identified using the neighboring score method. The recursive feature elimination (RFE) algorithm was employed to select the risk genes among feature genes, which were subsequently applied to perform a support vector machine (SVM) classifier to identify the specific signature in myocardial infarction samples. Another dataset, GSE61144, was also downloaded to verify the efficacy of the classifier. A total of 724 downregulated and 483 upregulated DEGs were screened in patient samples compared with control samples in the GSE34198 dataset. The PPI network of myocardial infarction was comprised of 1,083 nodes (genes) and 46,363 lines (connections). Using the neighborhood scoring method, the top 100 feature genes in myocardial infarction samples were identified as the disease feature genes, which distinguish the myocardial infarction samples from the control samples. The RFE algorithm screened 15 risk genes, which were employed to construct a SVM classifier with an average precision of 88% to the patient sample following visualization by a confusion matrix. The predictive precision of the classifier on another microarray dataset, GSE61144, was 0.92, with an average true positive of 0.9278 and an average false positive of 0.2361. A‑kinase‑anchoring protein 12 (AKAP12) and glycine receptor α2 (GLRA2) were two risk genes in the SVM classifier. Therefore, AKAP12 and GLRA2 exert potential roles in the development of myocardial infarction, potentially by influencing cardiac contractility and protecting against ischemia‑reperfusion injury, which may provide clues in developing potential diagnostic biomarkers or therapeutic targets for myocardial infarction.
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