title: Gene set bagging for estimating the probability a statistically significant result will replicate.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  Using both simulated and publicly-available genomics data, we demonstrate that significant categories in a gene set enrichment analysis may be unstable when subjected to resampling. We show our method estimates the replication probability (R), the probability that a gene set will replicate as a significant result in future studies, and show in simulations that this method reflects replication better than each set's p-value.
  
  
  CONCLUSIONS
  Our results suggest that gene lists based on p-values are not necessarily stable, and therefore additional steps like gene set bagging may improve biological inference on gene sets.
authors: Andrew E
authors: AE
authors: Jaffe
authors: John D
authors: JD
authors: Storey
authors: Hongkai
authors: H
authors: Ji
authors: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore MD 21205, USA. jleek@jhsph.edu.
authors: Jeffrey T
authors: JT
authors: Leek
mesh_terms: D000465:Algorithms; D001665:Binding Sites / Q000235:genetics; D001923:Brain Chemistry / Q000235:genetics; D003198:Computer Simulation; D019175:DNA Methylation / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D016208:Databases, Factual; D020869:Gene Expression Profiling / Q000379:methods; D015894:Genome, Human; D023281:Genomics / Q000379:methods* / Q000639:trends; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011237:Predictive Value of Tests; D011336:Probability; D018401:Sample Size; D012907:Smoking / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors