Interpretation, design, and analysis of gene array expression experiments

Experiments using arrays of cDNA targets to compare patterns of gene expres sion are beginning to play a prominent role in biogerontology, but drawing reliable conclusions from the resulting data sets requires careful applicat ion of statistical methods that discriminate chance events from those likel y to reflect real differences among the samples under study. This essay dis cusses flaws in the logic of studies that base their conclusions on ratio c alculations alone, reviews the multiple comparison traps inherent in high t hroughput systems that test a very large number of mRNAs simultaneously, an d advocates a two-stage design in which significance testing applied to exp loratory data is used to guide a second round of hypothesis-testing experim ents conducted in a separate set of experimental samples.