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Bioinformatics Advance Access published online on February 10, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti316
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© The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received October 13, 2004
Revised February 4, 2005
Accepted February 7, 2005

Article

Bio-Object, a stochastic simulator for post-transcriptional regulation

Nobukazu Ohki 1 and Masatoshi Hagiwara 2*

1 Department of Functional Genomics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan
2 Department of Functional Genomics, Medical Research Institute, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan; Laboratory of Gene Expression, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan

* To whom correspondence should be addressed.
Masatoshi Hagiwara, E-mail: m.hagiwara.end{at}mri.tmd.ac.jp


  Abstract

Motivation: Recently, biologists learned that the transport and degradation of transcribed mRNA and protein present critically important steps for the regulation of gene expression through the extensive studies of RNAi (RNA interference), NMD (none-sense mediated decay) and ubiquitination. However, adequate considerations of these factors have not been given in the past in silico analysis compared with transcriptional regulations.

Results: We have newly developed a bio-system simulator "Bio-Object" and assessed the contribution of numerous factors including movements, stability, and interactions of both mRNAs and proteins in the virtual cell space to the Drosophila circadian rhythm. The oscillations of period (per), timeless (tim) and Drosophila Clock (dClk) mRNAs and proteins predicted by the simulations have agreed with the observed data in Drosophila and were lost with the knock out of either per or dClk gene as observed experimentally. Bio-Object newly predicts that (i) the stability of dClk mRNA, (ii) the stability of dCLK, and (iii) the affinity of PER-TIM complex are determinants of the circadian duration.

Availability: Source code is available for download from http://www.tmd.ac.jp/mri/mri-end/bio-object/download/.

Supplementary information: Detailed explanation of Bio-Object is available at http://www.tmd.ac.jp/mri/mri-end/bio-object/.


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