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BMC Genomics

, 9:375

First Online: 06 August 2008Received: 25 March 2008Accepted: 06 August 2008

Abstract

BackgroundMichiels et al. Lancet 2005; 365: 488–92 employed a resampling strategy to show that the genes identified as predictors of prognosis from resamplings of a single gene expression dataset are highly variable. The genes most frequently identified in the separate resamplings were put forward as a -gold standard-. On a higher level, breast cancer datasets collected by different institutions can be considered as resamplings from the underlying breast cancer population. The limited overlap between published prognostic signatures confirms the trend of signature instability identified by the resampling strategy. Six breast cancer datasets, totaling 947 samples, all measured on the Affymetrix platform, are currently available. This provides a unique opportunity to employ a substantial dataset to investigate the effects of pooling datasets on classifier accuracy, signature stability and enrichment of functional categories.

ResultsWe show that the resampling strategy produces a suboptimal ranking of genes, which can not be considered to be a -gold standard-. When pooling breast cancer datasets, we observed a synergetic effect on the classification performance in 73% of the cases. We also observe a significant positive correlation between the number of datasets that is pooled, the validation performance, the number of genes selected, and the enrichment of specific functional categories. In addition, we have evaluated the support for five explanations that have been postulated for the limited overlap of signatures.

ConclusionThe limited overlap of current signature genes can be attributed to small sample size. Pooling datasets results in more accurate classification and a convergence of signature genes. We therefore advocate the analysis of new data within the context of a compendium, rather than analysis in isolation.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-9-375 contains supplementary material, which is available to authorized users.

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Autor: Martin H van Vliet - Fabien Reyal - Hugo M Horlings - Marc J van de Vijver - Marcel JT Reinders - Lodewyk FA Wessels

Fuente: https://link.springer.com/article/10.1186/1471-2164-9-375



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