title: A statistical method for the conservative adjustment of false discovery rate (q-value).
abstract: BACKGROUND
  q-value is a widely used statistical method for estimating false discovery rate (FDR), which is a conventional significance measure in the analysis of genome-wide expression data. q-value is a random variable and it may underestimate FDR in practice. An underestimated FDR can lead to unexpected false discoveries in the follow-up validation experiments. This issue has not been well addressed in literature, especially in the situation when the permutation procedure is necessary for p-value calculation.
  
  
  RESULTS
  We proposed a statistical method for the conservative adjustment of q-value. In practice, it is usually necessary to calculate p-value by a permutation procedure. This was also considered in our adjustment method. We used simulation data as well as experimental microarray or sequencing data to illustrate the usefulness of our method.
  
  
  CONCLUSIONS
  The conservativeness of our approach has been mathematically confirmed in this study. We have demonstrated the importance of conservative adjustment of q-value, particularly in the situation that the proportion of differentially expressed genes is small or the overall differential expression signal is weak.
authors.affiliation: Department of Statistics and Biostatistics Center, The George Washington University, Washington D.C., 20052, USA. ylai@gwu.edu.
authors.forename: Yinglei
authors.initials: Y
authors.lastname: Lai
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005189:False Positive Reactions; D056726:Genetic Association Studies; D015894:Genome, Human; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D015233:Models, Statistical; D011471:Prostatic Neoplasms / Q000235:genetics; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA
keywords: Conservative adjustment; False discovery rate; q-value