title: Modified nonparametric approaches to detecting differentially expressed genes in replicated microarray experiments.
abstract: BACKGROUND
  An important goal in analyzing microarray data is to determine which genes are differentially expressed across two kinds of tissue samples or samples obtained under two experimental conditions. Various parametric tests, such as the two-sample t-test, have been used, but their possibly too strong parametric assumptions or large sample justifications may not hold in practice. As alternatives, a class of three nonparametric statistical methods, including the empirical Bayes method of Efron et al. (2001), the significance analysis of microarray (SAM) method of Tusher et al. (2001) and the mixture model method (MMM) of Pan et al. (2001), have been proposed. All the three methods depend on constructing a test statistic and a so-called null statistic such that the null statistic's distribution can be used to approximate the null distribution of the test statistic. However, relatively little effort has been directed toward assessment of the performance or the underlying assumptions of the methods in constructing such test and null statistics.
  
  
  RESULTS
  We point out a problem of a current method to construct the test and null statistics, which may lead to largely inflated Type I errors (i.e. false positives). We also propose two modifications that overcome the problem. In the context of MMM, the improved performance of the modified methods is demonstrated using simulated data. In addition, our numerical results also provide evidence to support the utility and effectiveness of MMM.
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, MMC 303, A460 Mayo Building, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid