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

Tópicos

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Resumo

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.

Resumo Limpo

discoveri novel diseas biomark crucial challeng translat bioinformat demonstr classif power reproduc across independ dataset essenti requir assess potenti clinic relev small dataset multipl putat biomark set may explain lack predict reproduc studi base pathwaydriven discoveri approach suggest despit discrep result putat biomark tend implic common biolog process investig problem main focus dataset deriv cancer research investig predict function concord five method discov putat biomark four independentlygener dataset cardiovascular diseas domain divers biosignatur identifi differ method howev found strong biolog process concord especi case method base gene set analysi except observ lack classif reproduc use independ dataset partial overlap putat set biomark primari studi exist despit observ limit pathwaydriven gene set analysi can predict potenti novel biomark can joint point biomedicallyrelev under molecular mechan

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