Conditional Moment Closure Schemes for Studying Stochastic Dynamics of Genetic Circuits

IEEE Transactions on Biomedical Circuits and Systems
Mohammad SoltaniAbhyudai Singh

Abstract

Inside individual cells, stochastic expression drives random fluctuations in gene product copy numbers, which corrupts functioning of both natural and synthetic genetic circuits. Dynamic models of genetic circuits are formulated stochastically using the chemical master equation framework. Since obtaining probability distributions can be computationally expensive in these models, noise is typically investigated through lower-order statistical moments (mean, variance, correlation, skewness, etc.) of mRNA/proteins levels. However, due to the nonlinearities in genetic circuits, this moment dynamics is typically not closed, in the sense that the time derivative of the lower-order statistical moments depends on high-order moments. Moment equations are closed by expressing higher-order moments as nonlinear functions of lower-order moments, a technique commonly referred to as moment closure. We provide a new moment closure scheme for studying stochastic dynamics of genetic circuits, where genes randomly toggle between transcriptionally active and inactive states. The method is based on conditioning protein levels on active states of genes and then expressing higher-order moments as functions of lower-order conditional moments. The cond...Continue Reading

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Citations

Jan 23, 2016·IEEE Transactions on Biomedical Circuits and Systems·Chih-Yuan HsuBor-Sen Chen
Oct 21, 2016·IET Systems Biology·Alessandro BorriAbhyudai Singh
Aug 19, 2016·PLoS Computational Biology·Mohammad SoltaniAbhyudai Singh
Oct 23, 2016·BMC Systems Biology·Alexander Lück, Verena Wolf
Jul 1, 2017·Physical Biology·Khem Raj GhusingaAbhyudai Singh
Apr 4, 2019·Journal of the Royal Society, Interface·Zhixing Cao, Ramon Grima
Aug 19, 2018·Nature Communications·Zhixing Cao, Ramon Grima
Jan 14, 2017·Royal Society Open Science·Mohammad Soltani, Abhyudai Singh
Nov 21, 2020·Physical Review. E·Yan-Mei Kang, Ruo-Nan Liu
Jun 26, 2021·Bioinformatics·Augustinas Sukys, Ramon Grima
Aug 13, 2021·PloS One·Abhyudai Singh

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