Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA.
IEEE Trans Biomed Eng. 2012 Jun;59(6):1701-10. doi: 10.1109/TBME.2012.2192117. Epub 2012 Apr 3.
We present a procedure to generate a stochastic genetic regulatory network model consistent with pathway information. Using the stochastic dynamics of Markov chains, we produce a model constrained by the prior knowledge despite the sometimes incomplete, time independent, and often conflicting nature of these pathways. We apply the Markov theory to study the model's long run behavior and introduce a biologically important transformation to aid in comparison with real biological outcome prediction in the steady-state domain. Our technique produces biologically faithful models without the need for rate kinetics, detailed timing information, or complex inference procedures. To demonstrate the method, we produce a model using 28 pathways from the biological literature pertaining to the transcription factor family nuclear factor-κB. Predictions from this model in the steady-state domain are then validated against nine mice knockout experiments.
我们提出了一种生成与途径信息一致的随机遗传调控网络模型的方法。利用马尔可夫链的随机动力学,我们生成了一个模型,该模型受到先验知识的约束,尽管这些途径有时是不完整的、与时间无关的,而且往往是相互矛盾的。我们应用马尔可夫理论来研究模型的长期行为,并引入了一种生物学上重要的变换,以帮助在稳态域中与真实的生物学结果预测进行比较。我们的技术产生了具有生物学意义的模型,而不需要速率动力学、详细的定时信息或复杂的推理过程。为了演示该方法,我们使用来自生物学文献中与转录因子家族核因子-κB 相关的 28 条途径生成了一个模型。然后,该模型在稳态域中的预测结果与九项小鼠敲除实验进行了验证。