Hey Kirsty L, Momiji Hiroshi, Featherstone Karen, Davis Julian R E, White Michael R H, Rand David A, Finkenstädt Bärbel
Department of Statistics, University of Warwick, Coventry CV4 7AL, UK.
Warwick Systems Biology, University of Warwick, Coventry CV4 7AL, UK.
Biostatistics. 2015 Oct;16(4):655-69. doi: 10.1093/biostatistics/kxv010. Epub 2015 Mar 26.
Gene expression is made up of inherently stochastic processes within single cells and can be modeled through stochastic reaction networks (SRNs). In particular, SRNs capture the features of intrinsic variability arising from intracellular biochemical processes. We extend current models for gene expression to allow the transcriptional process within an SRN to follow a random step or switch function which may be estimated using reversible jump Markov chain Monte Carlo (MCMC). This stochastic switch model provides a generic framework to capture many different dynamic features observed in single cell gene expression. Inference for such SRNs is challenging due to the intractability of the transition densities. We derive a model-specific birth-death approximation and study its use for inference in comparison with the linear noise approximation where both approximations are considered within the unifying framework of state-space models. The methodology is applied to synthetic as well as experimental single cell imaging data measuring expression of the human prolactin gene in pituitary cells.
基因表达由单细胞内固有的随机过程组成,可通过随机反应网络(SRN)进行建模。特别是,SRN捕捉了细胞内生化过程产生的内在变异性特征。我们扩展了当前的基因表达模型,使SRN中的转录过程遵循随机步长或切换函数,这可以使用可逆跳跃马尔可夫链蒙特卡罗(MCMC)进行估计。这种随机切换模型提供了一个通用框架,以捕捉在单细胞基因表达中观察到的许多不同动态特征。由于转移密度的难处理性,对此类SRN的推断具有挑战性。我们推导了一种特定于模型的生死近似,并研究其在推断中的应用,与线性噪声近似进行比较,其中两种近似都在状态空间模型的统一框架内进行考虑。该方法应用于合成以及实验性单细胞成像数据,这些数据测量了垂体细胞中人催乳素基因的表达。