Identification of significant periodic genes in microarray gene expression data

Based on two statistical hypothesis testing methods for identifying periodic time series, a novel statistical inference approach, the C&G procedure, is proposed to effectively screen out statistically significantly periodically expressed genes. The approach is then applied to yeast and bacterial cell cycle gene expression data sets, as well as to human fibroblasts and human cancer cell line data sets, and significantly periodically expressed genes are successfully identified.The C&G procedure proposed is an effective method for identifying statistically significant periodic genes in microarray time series gene expression data.Microarray experiments are widely used for gene profiling in different cell lines, various tissues, and conditions (normal versus cancerous). High throughput microarray technologies have made it possible to study problems that range from gene regulation and mRNA stability, to pathways for genetic diseases and the discovery of target subpopulations for drug or other therapies. One frequent application of microarray experiments is in the study of monitoring gene activities in a cell during cell cycle or cell division. A new challenge to statisticians for analyzing the microarray experiments is to identify genes that are statistically significantly periodically expressed during the cell cycle. Such a challenge occurs due to the large number of genes that are simultaneously measured, a moderate to small number of measurements per gene taken at different time points, and high levels of non-normal random noises inherited in the data (Wichert [1]). Several authors, including Spellman [2], Cho [3], Shedden and Cooper [4,5], Whitfield [6] have noticed the presence of cyclicity or periodicity of genes in their microarray data sets and used a number of ways to identify periodically expressed genes in some available yeast and human cell cycle data sets obtained by them. There are some debates concerning the methods those authors used in finding the cyclic