Bioinformatics Advance Access published online on January 19, 2007
Bioinformatics, doi:10.1093/bioinformatics/btl667
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A hidden Markov model-based approach for identifying timing differences in gene expression under different experimental factors
aBioinformatics Center, Kyoto University, Gokasho Uji, 611-0011, Japan, bPharmaceutical Research Laboratories, Pharmaceutical Division, Kirin Brewery Co. Ltd, 3 Miyahara, Takasaki, Gunma 370-1295, Japan
*To whom correspondence should be addressed. Takashi Yoneya, E-mail: t-yoneya{at}kirin.co.jp
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Abstract |
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Motivation: Time series experiments of cDNA microarray 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 a general timing difference which 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 that 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 an 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 a timing ordering under different experimental factors, such as that gene expression under Heat shock tended to start earlier than that under Oxidative stress.
Associate Editor: Satoru Miyano
Received on October 23, 2006; revised on December 1, 2006; accepted on December 28, 2006
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