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MetaKTSP: a meta-analytic top scoring pair method for robust cross-study validation of omics prediction analysis.

ABSTRACT: MOTIVATION:Supervised machine learning is widely applied to transcriptomic data to predict disease diagnosis, prognosis or survival. Robust and interpretable classifiers with high accuracy are usually favored for their clinical and translational potential. The top scoring pair (TSP) algorithm is an example that applies a simple rank-based algorithm to identify rank-altered gene pairs for classifier construction. Although many classification methods perform well in cross-validation of single expression profile, the performance usually greatly reduces in cross-study validation (i.e. the prediction model is established in the training study and applied to an independent test study) for all machine learning methods, including TSP. The failure of cross-study validation has largely diminished the potential translational and clinical values of the models. The purpose of this article is to develop a meta-analytic top scoring pair (MetaKTSP) framework that combines multiple transcriptomic studies and generates a robust prediction model applicable to independent test studies. RESULTS:We proposed two frameworks, by averaging TSP scores or by combining P-values from individual studies, to select the top gene pairs for model construction. We applied the proposed methods in simulated data sets and three large-scale real applications in breast cancer, idiopathic pulmonary fibrosis and pan-cancer methylation. The result showed superior performance of cross-study validation accuracy and biomarker selection for the new meta-analytic framework. In conclusion, combining multiple omics data sets in the public domain increases robustness and accuracy of the classification model that will ultimately improve disease understanding and clinical treatment decisions to benefit patients. AVAILABILITY AND IMPLEMENTATION:An R package MetaKTSP is available online. (http://tsenglab.biostat.pitt.edu/software.htm). CONTACT:ctseng@pitt.edu SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.

SUBMITTER: Kim S

PROVIDER: S-EPMC6280887 | biostudies-other | 2016 Jul

REPOSITORIES: biostudies-other

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MetaKTSP: a meta-analytic top scoring pair method for robust cross-study validation of omics prediction analysis.

Kim SungHwan S Lin Chien-Wei CW Tseng George C GC

Bioinformatics (Oxford, England) 20160302 13

<h4>Motivation</h4>Supervised machine learning is widely applied to transcriptomic data to predict disease diagnosis, prognosis or survival. Robust and interpretable classifiers with high accuracy are usually favored for their clinical and translational potential. The top scoring pair (TSP) algorithm is an example that applies a simple rank-based algorithm to identify rank-altered gene pairs for classifier construction. Although many classification methods perform well in cross-validation of sin ...[more]

PMID: 27153719

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Project description:BackgroundThe widely used k top scoring pair (k-TSP) algorithm is a simple yet powerful parameter-free classifier. It owes its success in many cancer microarray datasets to an effective feature selection algorithm that is based on relative expression ordering of gene pairs. However, its general robustness does not extend to some difficult datasets, such as those involving cancer outcome prediction, which may be due to the relatively simple voting scheme used by the classifier. We believe that the performance can be enhanced by separating its effective feature selection component and combining it with a powerful classifier such as the support vector machine (SVM). More generally the top scoring pairs generated by the k-TSP ranking algorithm can be used as a dimensionally reduced subspace for other machine learning classifiers.ResultsWe developed an approach integrating the k-TSP ranking algorithm (TSP) with other machine learning methods, allowing combination of the computationally efficient, multivariate feature ranking of k-TSP with multivariate classifiers such as SVM. We evaluated this hybrid scheme (k-TSP+SVM) in a range of simulated datasets with known data structures. As compared with other feature selection methods, such as a univariate method similar to Fisher's discriminant criterion (Fisher), or a recursive feature elimination embedded in SVM (RFE), TSP is increasingly more effective than the other two methods as the informative genes become progressively more correlated, which is demonstrated both in terms of the classification performance and the ability to recover true informative genes. We also applied this hybrid scheme to four cancer prognosis datasets, in which k-TSP+SVM outperforms k-TSP classifier in all datasets, and achieves either comparable or superior performance to that using SVM alone. In concurrence with what is observed in simulation, TSP appears to be a better feature selector than Fisher and RFE in some of the cancer datasetsConclusionsThe k-TSP ranking algorithm can be used as a computationally efficient, multivariate filter method for feature selection in machine learning. SVM in combination with k-TSP ranking algorithm outperforms k-TSP and SVM alone in simulated datasets and in some cancer prognosis datasets. Simulation studies suggest that as a feature selector, it is better tuned to certain data characteristics, i.e. correlations among informative genes, which is potentially interesting as an alternative feature ranking method in pathway analysis.

Dataset Information

MetaKTSP: a meta-analytic top scoring pair method for robust cross-study validation of omics prediction analysis.

Publications

MetaKTSP: a meta-analytic top scoring pair method for robust cross-study validation of omics prediction analysis.

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