Bootstrapping of gene-expression data improves and controls the false discovery rate of differentially expressed genes

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Meuwissen, Theo | Goddard, Mike

Edité par CCSD ; BioMed Central -

International audience. The ordinary-, penalized-, and bootstrap $t$-test, least squares and best linear unbiased prediction were compared for their false discovery rates (FDR), i.e. the fraction of falsely discovered genes, which was empirically estimated in a duplicate of the data set. The bootstrap-$t$-test yielded up to 80% lower FDRs than the alternative statistics, and its FDR was always as good as or better than any of the alternatives. Generally, the predicted FDR from the bootstrapped $P$-values agreed well with their empirical estimates, except when the number of mRNA samples is smaller than 16. In a cancer data set, the bootstrap-$t$-test discovered 200 differentially regulated genes at a FDR of 2.6%, and in a knock-out gene expression experiment 10 genes were discovered at a FDR of 3.2%. It is argued that, in the case of microarray data, control of the FDR takes sufficient account of the multiple testing, whilst being less stringent than Bonferoni-type multiple testing corrections. Extensions of the bootstrap simulations to more complicated test-statistics are discussed.

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