Systems-based biological concordance and predictive reproducibility of gene set discovery methods in cardiovascular disease

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Abstract

The discovery of novel disease biomarkers is a crucial challenge for translational bioinformatics. Demonstration of both their classification power and reproducibility across independent datasets are essential requirements to assess their potential clinical relevance. Small datasets and multiplicity of putative biomarker sets may explain lack of predictive reproducibility. Studies based on pathway-driven discovery approaches have suggested that, despite such discrepancies, the resulting putative biomarkers tend to be implicated in common biological processes. Investigations of this problem have been mainly focused on datasets derived from cancer research. We investigated the predictive and. functional concordance of five methods for discovering putative biomarkers in four independently-generated datasets from the cardiovascular disease domain. A diversity of biosignatures was identified by the different methods. However, we found strong biological process concordance between them, especially in the case of methods based on gene set analysis. With a few exceptions, we observed lack of classification reproducibility using independent datasets. Partial overlaps between our putative sets of biomarkers and the primary studies exist. Despite the observed limitations, pathway-driven or gene set analysis can predict potentially novel biomarkers and can jointly point to biomedically-relevant underlying molecular mechanisms. © 2011 Elsevier Inc.

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Azuaje, F., Zheng, H., Camargo, A., & Wang, H. (2011). Systems-based biological concordance and predictive reproducibility of gene set discovery methods in cardiovascular disease. Journal of Biomedical Informatics, 44(4), 637–647. https://doi.org/10.1016/j.jbi.2011.02.003

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