Significance analysis plays a major role in identifying and ranking genes, transcription factor binding sites, DNA methylation regions, and other high-throughput features associated with illness. We propose a new approach, called gene set bagging, for measuring the probability that a gene set replicates in future studies. Gene set bagging involves resampling the original high-throughput data, performing gene-set analysis on the resampled data, and confirming that biological categories replicate in the bagged samples.