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Filter and Wrapper Stacking Ensemble (FWSE): a robust approach for reliable biomarker discovery in high-dimensional omics data.

ABSTRACT: Selecting informative features, such as accurate biomarkers for disease diagnosis, prognosis and response to treatment, is an essential task in the field of bioinformatics. Medical data often contain thousands of features and identifying potential biomarkers is challenging due to small number of samples in the data, method dependence and non-reproducibility. This paper proposes a novel ensemble feature selection method, named Filter and Wrapper Stacking Ensemble (FWSE), to identify reproducible biomarkers from high-dimensional omics data. In FWSE, filter feature selection methods are run on numerous subsets of the data to eliminate irrelevant features, and then wrapper feature selection methods are applied to rank the top features. The method was validated on four high-dimensional medical datasets related to mental illnesses and cancer. The results indicate that the features selected by FWSE are stable and statistically more significant than the ones obtained by existing methods while also demonstrating biological relevance. Furthermore, FWSE is a generic method, applicable to various high-dimensional datasets in the fields of machine intelligence and bioinformatics.

SUBMITTER: Budhraja S

PROVIDER: S-EPMC10605029 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Filter and Wrapper Stacking Ensemble (FWSE): a robust approach for reliable biomarker discovery in high-dimensional omics data.

Budhraja Sugam S Doborjeh Maryam M Singh Balkaran B Tan Samuel S Doborjeh Zohreh Z Lai Edmund E Merkin Alexander A Lee Jimmy J Goh Wilson W Kasabov Nikola N

Briefings in bioinformatics 20230901 6

Selecting informative features, such as accurate biomarkers for disease diagnosis, prognosis and response to treatment, is an essential task in the field of bioinformatics. Medical data often contain thousands of features and identifying potential biomarkers is challenging due to small number of samples in the data, method dependence and non-reproducibility. This paper proposes a novel ensemble feature selection method, named Filter and Wrapper Stacking Ensemble (FWSE), to identify reproducible ...[more]

PMID: 37889118

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Project description:Microarray technology is known as one of the most important tools for collecting DNA expression data. This technology allows researchers to investigate and examine types of diseases and their origins. However, microarray data are often associated with a small sample size, a significant number of genes, imbalanced data, etc., making classification models inefficient. Thus, a new hybrid solution based on a multi-filter and adaptive chaotic multi-objective forest optimization algorithm (AC-MOFOA) is presented to solve the gene selection problem and construct the Ensemble Classifier. In the proposed solution, a multi-filter model (i.e., ensemble filter) is proposed as preprocessing step to reduce the dataset's dimensions, using a combination of five filter methods to remove redundant and irrelevant genes. Accordingly, the results of the five filter methods are combined using a voting-based function. Additionally, the results of the proposed multi-filter indicate that it has good capability in reducing the gene subset size and selecting relevant genes. Then, an AC-MOFOA based on the concepts of non-dominated sorting, crowding distance, chaos theory, and adaptive operators is presented. AC-MOFOA as a wrapper method aimed at reducing dataset dimensions, optimizing KELM, and increasing the accuracy of the classification, simultaneously. Next, in this method, an ensemble classifier model is presented using AC-MOFOA results to classify microarray data. The performance of the proposed algorithm was evaluated on nine public microarray datasets, and its results were compared in terms of the number of selected genes, classification efficiency, execution time, time complexity, hypervolume indicator, and spacing metric with five hybrid multi-objective methods, and three hybrid single-objective methods. According to the results, the proposed hybrid method could increase the accuracy of the KELM in most datasets by reducing the dataset's dimensions and achieve similar or superior performance compared to other multi-objective methods. Furthermore, the proposed Ensemble Classifier model could provide better classification accuracy and generalizability in the seven of nine microarray datasets compared to conventional ensemble methods. Moreover, the comparison results of the Ensemble Classifier model with three state-of-the-art ensemble generation methods indicate its competitive performance in which the proposed ensemble model achieved better results in the five of nine datasets.Supplementary informationThe online version contains supplementary material available at 10.1007/s00521-021-06459-9.

Project description:BackgroundBiomarker detection presents itself as a major means of translating biological data into clinical applications. Due to the recent advances in high throughput sequencing technologies, an increased number of metagenomics studies have suggested the dysbiosis in microbial communities as potential biomarker for certain diseases. The reproducibility of the results drawn from metagenomic data is crucial for clinical applications and to prevent incorrect biological conclusions. The variability in the sample size and the subjects participating in the experiments induce diversity, which may drastically change the outcome of biomarker detection algorithms. Therefore, a robust biomarker detection algorithm that ensures the consistency of the results irrespective of the natural diversity present in the samples is needed.ResultsToward this end, this paper proposes a novel Regularized Low Rank-Sparse Decomposition (RegLRSD) algorithm. RegLRSD models the bacterial abundance data as a superposition between a sparse matrix and a low-rank matrix, which account for the differentially and non-differentially abundant microbes, respectively. Hence, the biomarker detection problem is cast as a matrix decomposition problem. In order to yield more consistent and solid biological conclusions, RegLRSD incorporates the prior knowledge that the irrelevant microbes do not exhibit significant variation between samples belonging to different phenotypes. Moreover, an efficient algorithm to extract the sparse matrix is proposed. Comprehensive comparisons of RegLRSD with the state-of-the-art algorithms on three realistic datasets are presented. The obtained results demonstrate that RegLRSD consistently outperforms the other algorithms in terms of reproducibility performance and provides a marker list with high classification accuracy.ConclusionsThe proposed RegLRSD algorithm for biomarker detection provides high reproducibility and classification accuracy performance regardless of the dataset complexity and the number of selected biomarkers. This renders RegLRSD as a reliable and powerful tool for identifying potential metagenomic biomarkers.

Project description:MotivationTissue-level omics data such as transcriptomics and epigenomics are an average across diverse cell types. To extract cell-type-specific (CTS) signals, dozens of cellular deconvolution methods have been proposed to infer cell-type fractions from tissue-level data. However, these methods produce vastly different results under various real data settings. Simulation-based benchmarking studies showed no universally best deconvolution approaches. There have been attempts of ensemble methods, but they only aggregate multiple single-cell references or reference-free deconvolution methods.ResultsTo achieve a robust estimation of cellular fractions, we proposed EnsDeconv (Ensemble Deconvolution), which adopts CTS robust regression to synthesize the results from 11 single deconvolution methods, 10 reference datasets, 5 marker gene selection procedures, 5 data normalizations and 2 transformations. Unlike most benchmarking studies based on simulations, we compiled four large real datasets of 4937 tissue samples in total with measured cellular fractions and bulk gene expression from different tissues. Comprehensive evaluations demonstrated that EnsDeconv yields more stable, robust and accurate fractions than existing methods. We illustrated that EnsDeconv estimated cellular fractions enable various CTS downstream analyses such as differential fractions associated with clinical variables. We further extended EnsDeconv to analyze bulk DNA methylation data.Availability and implementationEnsDeconv is freely available as an R-package from https://github.com/randel/EnsDeconv. The RNA microarray data from the TRAUMA study are available and can be accessed in GEO (GSE36809). The demographic and clinical phenotypes can be shared on reasonable request to the corresponding authors. The RNA-seq data from the EVAPR study cannot be shared publicly due to the privacy of individuals that participated in the clinical research in compliance with the IRB approval at the University of Pittsburgh. The RNA microarray data from the FHS study are available from dbGaP (phs000007.v32.p13). The RNA-seq data from ROS study is downloaded from AD Knowledge Portal.Supplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

Filter and Wrapper Stacking Ensemble (FWSE): a robust approach for reliable biomarker discovery in high-dimensional omics data.

Publications

Filter and Wrapper Stacking Ensemble (FWSE): a robust approach for reliable biomarker discovery in high-dimensional omics data.

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