生物对象，一种用于转录后调控的随机模拟器。

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

作者信息

Ohki Nobukazu, Hagiwara Masatoshi

机构信息

Department of Functional Genomics, Medical Research Institute, 1-5-45 Yushima, Tokyo 113-0034, Japan.

出版信息

Bioinformatics. 2005 May 15;21(10):2478-87. doi: 10.1093/bioinformatics/bti316. Epub 2005 Feb 10.

DOI:10.1093/bioinformatics/bti316

PMID:15705653

Abstract

MOTIVATION

Recently, biologists learnt that the transport and degradation of transcribed mRNA and protein present critically important steps for the regulation of gene expression through extensive studies of RNA interference, none-sense mediated decay and ubiquitination. However, adequate consideration of these factors has not been done in the past in in silico analysis compared with transcriptional regulations.

RESULTS

We have 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 agreed with the observed data in Drosophila and were lost with the knock-out of either the per or the dClk gene as observed experimentally. Bio-Object predicts that (1) the stability of dClk mRNA, (2) the stability of dCLK and (3) the affinity of the PER-TIM complex are determinants of the circadian duration.

AVAILABILITY

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

摘要

动机

最近，生物学家通过对RNA干扰、无义介导的衰变和泛素化的广泛研究了解到，转录的mRNA和蛋白质的运输与降解是基因表达调控的关键步骤。然而，与转录调控相比，过去在计算机分析中并未充分考虑这些因素。

结果

我们开发了一个生物系统模拟器“Bio-Object”，并评估了包括mRNA和蛋白质在虚拟细胞空间中的运动、稳定性及相互作用等众多因素对果蝇昼夜节律的贡献。模拟预测的周期（per）、无时间（tim）和果蝇时钟（dClk）mRNA及蛋白质的振荡与果蝇中的观测数据一致，并且如实验观察到的那样，在per或dClk基因敲除后消失。Bio-Object预测：（1）dClk mRNA的稳定性，（2）dCLK的稳定性，以及（3）PER-TIM复合物的亲和力是昼夜节律时长的决定因素。