title: Detecting differential expression in microarray data: comparison of optimal procedures.
abstract: BACKGROUND
  Many procedures for finding differentially expressed genes in microarray data are based on classical or modified t-statistics. Due to multiple testing considerations, the false discovery rate (FDR) is the key tool for assessing the significance of these test statistics. Two recent papers have generalized two aspects: Storey et al. (2005) have introduced a likelihood ratio test statistic for two-sample situations that has desirable theoretical properties (optimal discovery procedure, ODP), but uses standard FDR assessment; Ploner et al. (2006) have introduced a multivariate local FDR that allows incorporation of standard error information, but uses the standard t-statistic (fdr2d). The relationship and relative performance of these methods in two-sample comparisons is currently unknown.
  
  
  METHODS
  Using simulated and real datasets, we compare the ODP and fdr2d procedures. We also introduce a new procedure called S2d that combines the ODP test statistic with the extended FDR assessment of fdr2d.
  
  
  RESULTS
  For both simulated and real datasets, fdr2d performs better than ODP. As expected, both methods perform better than a standard t-statistic with standard local FDR. The new procedure S2d performs as well as fdr2d on simulated data, but performs better on the real data sets.
  
  
  CONCLUSIONS
  The ODP can be improved by including the standard error information as in fdr2d. This means that the optimality enjoyed in theory by ODP does not hold for the estimated version that has to be used in practice. The new procedure S2d has a slight advantage over fdr2d, which has to be balanced against a significantly higher computational effort and a less intuititive test statistic.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden. lenaperelman@gmail.com <lenaperelman@gmail.com>
authors.forename: Elena
authors.initials: E
authors.lastname: Perelman
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploner
authors.forename: Stefano
authors.initials: S
authors.lastname: Calza
authors.forename: Yudi
authors.initials: Y
authors.lastname: Pawitan
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D020869:Gene Expression Profiling / Q000295:instrumentation* / Q000379:methods*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012984:Software