Cell cycle analysis and microarrays

A recent profusion of microarray analysis of gene expression during the cell division cycle raises questions as to whether statistical problems with the data analysis have been considered. Two non-scientific examples – ESP and the Bible Code – illustrate the problem. Individuals with extrasensory perception (ESP) were identified by their ability to guess pictograms in a deck of 25 cards. There were five different pictures so that random guessing would lead to an expectation of 20% correct. When thousands of individuals were tested, some guessed the cards correctly with a frequency greater than 20%. These individuals were proposed to have ‘ESP-ability’. Upon re-testing, some of these individuals repeated above-average guessing, whereas others did not. With central to all forms of Hirschsprung disease, although mutations in its coding regions have only been identified in 40% of linked families. Although the genes at the other two loci were not identified in this study, the authors suggest that they are modifiers of RET expression. The success of this and several other studies demonstrate that it is possible to identify susceptibility loci in complex genetic diseases using wholegenome-scanning approaches, especially in diseases where accurate phenotypic discrimination among subtypes is possible. (Gabriel, S. B. et al. [2002] Nat. Genet. DOI: 10.1038/ng868) AP