A hidden Markov model-based approach for identifying timing differences in gene expression under different experimental factors

MOTIVATION: Time series experiments of cDNA microarrays have been commonly used in various biological studies and conducted under a lot of experimental factors. A popular approach of time series microarray analysis is to compare one gene with another in their expression profiles, and clustering expression sequences is a typical example. On the other hand, a practically important issue in gene expression is to identify the general timing difference that is caused by experimental factors. This type of difference can be extracted by comparing a set of time series expression profiles under a factor with those under another factor, and so it would be difficult to tackle this issue by using only a current approach for time series microarray analysis. RESULTS: We have developed a systematic method to capture the timing difference in gene expression under different experimental factors, based on hidden Markov models. Our model outputs a real-valued vector at each state and has a unique state transition diagram. The parameters of our model are trained from a given set of pairwise (generally multiplewise) expression sequences. We evaluated our model using synthetic as well as real microarray datasets. The results of our experiment indicate that our method worked favourably to identify the timing ordering under different experimental factors, such as that gene expression under heat shock tended to start earlier than that under oxidative stress. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.