Liu Tian, Pei Yongzhen, Li Changguo, Ye Ming
School of Computer Science and Technology, Tiangong University, Tianjin 300387, China.
School of Computer Science and Technology, Tiangong University, Tianjin 300387, China; School of Mathematical Sciences, Tiangong University, Tianjin 300387, China.
Mol Ther Nucleic Acids. 2019 Dec 6;18:893-902. doi: 10.1016/j.omtn.2019.10.010. Epub 2019 Oct 18.
The amount of short interfering RNA (siRNA) escaping from the endosome has a significant impact on the efficiency of RNAi. In general, the initial injected amount of siRNAs during the experiment is known, and also the amount of siRNAs after the experiment can be revealed by the level of mRNA measured. However, it is impossible to measure the amount of siRNAs that escape from the endosome and really take part in the chemical reaction of RNAi by detecting the biological organism and its tissues. Inspired by the bottleneck effect in the virus, we introduce the Bayesian approach to infer the amount of escape based on a single type and multiple types of siRNA, respectively. With the consideration of the large calculation quantity of the accurate posterior distribution and the unavailable analytic expression of the likelihood function, our article proposes to take samples by the improved Markov chain Monte Carlo (MCMC) method. The article takes the silencing gene of the synthesis of chitin and the interfering multiple target oncogene as numerical examples to show that our improved MCMC method has higher operation efficiency compared to the Bayesian approach. Our research models siRNA endosome escape using statistical methods for the first time. It perhaps provides a theoretical basis to decrease the cost of a biotic experiment for the future and the standardized statistical approaches for the amount of escape estimation.
从内体逃逸的小干扰RNA(siRNA)的量对RNA干扰效率有重大影响。一般来说,实验期间初始注射的siRNA量是已知的,并且实验后siRNA的量也可以通过测量的mRNA水平来揭示。然而,通过检测生物有机体及其组织,无法测量从内体逃逸并真正参与RNA干扰化学反应的siRNA量。受病毒中瓶颈效应的启发,我们分别引入贝叶斯方法,基于单一类型和多种类型的siRNA来推断逃逸量。考虑到精确后验分布的计算量较大以及似然函数没有可用的解析表达式,我们的文章提出采用改进的马尔可夫链蒙特卡罗(MCMC)方法进行采样。文章以几丁质合成的沉默基因和干扰多个靶标癌基因作为数值示例,表明我们改进的MCMC方法与贝叶斯方法相比具有更高的运算效率。我们的研究首次使用统计方法对siRNA内体逃逸进行建模。它可能为未来降低生物实验成本以及逃逸量估计的标准化统计方法提供理论依据。