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Bioinformatics Advance Access originally published online on February 29, 2008
Bioinformatics 2008 24(8):1063-1069; doi:10.1093/bioinformatics/btn072
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Are we overestimating the number of cell-cycling genes? The impact of background models on time-series analysis

Matthias E. Futschik * and Hanspeter Herzel

Institute for Theoretical Biology, Charité, Humboldt-Universität, Invalidenstrasse 43, 10115 Berlin, Germany

*To whom correspondence should be addressed.


  Abstract

Motivation: Periodic processes play fundamental roles in organisms. Prominent examples are the cell cycle and the circadian clock. Microarray array technology has enabled us to screen complete sets of transcripts for possible association with such fundamental periodic processes on a system-wide level. Frequently, quite large numbers of genes have been detected as periodically expressed. However, the small overlap between genes identified in different studies has cast some doubts on the reliability of the periodic expression detected.

Results: In this study, comparative analysis suggests that the lacking agreement between different cell-cycle studies might be due to inadequate background models for the determination of significance. We demonstrate that the choice of background model has considerable impact on the statistical significance of periodic expression. For illustration, we reanalyzed two microarray studies of the yeast cell cycle. Our evaluation strongly indicates that the results of previous analyses might have been overoptimistic and that the use of more suitable background model promises to give more realistic results.

Availability: R scripts are available on request from the corresponding author.

Contact: matthias.futschik{at}charite.de

Supplementary information: Supplementary materials are available at Bioinformatics online.

Associate Editor: Dmitrij Frishman

Received on October 30, 2007; revised on February 20, 2008; accepted on February 20, 2008

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