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Published online 22 January 2004

Nucleic Acids Research, 2004, Vol. 32, No. 2 447-455
© 2004 Oxford University Press

Statistical resynchronization and Bayesian detection of periodically expressed genes

Xin Lu1, Wen Zhang1,2, Zhaohui S. Qin3, Kurt E. Kwast4 and Jun S. Liu*,1

1 Department of Statistics, Harvard University, Cambridge, MA 02138, USA, 2 Department of Biology, Kunming Medical College, Kunming 650031, China, 3 Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA and 4 Department of Molecular and Integrative Physiology, University of Illinois, Urbana, IL 61801, USA

*To whom correspondence should be addressed. Tel: +1 617 495 1600; Fax: +1 617 496 8057; Email: jliu{at}stat.harvard.edu
The authors wish it to be known that, in their opinion, the first two authors should be considered as joint First Authors

We propose a periodic–normal mixture (PNM) model to fit transcription profiles of periodically expressed (PE) genes in cell cycle microarray experiments. The model leads to a principled statistical estimation procedure that produces more accurate estimates of the mean cell cycle length and the gene expression periodicity than existing heuristic approaches. A central component of the proposed procedure is the resynchronization of the observed transcription profile of each PE gene according to the PNM with estimated periodicity parameters. By using a two-component mixture-Beta model to approximate the PNM fitting residuals, we employ an empirical Bayes method to detect PE genes. We estimate that about one-third of the genes in the genome of Saccharomyces cerevisiae are likely to be transcribed periodically, and identify 822 genes whose posterior probabilities of being PE are greater than 0.95. Among these 822 genes, 540 are also in the list of 800 genes detected by Spellman. Gene ontology annotation analysis shows that many of the 822 genes were involved in important cell cycle-related processes, functions and components. When matching the 822 resynchronized expression profiles of three independent experiments, little phase shifts were observed, indicating that the three synchronization methods might have brought cells to the same phase at the time of release.


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