Distinguishing the rates of gene activation from phenotypic variations

التفاصيل البيبلوغرافية
العنوان: Distinguishing the rates of gene activation from phenotypic variations
المؤلفون: Tiejun Li, Cheng Lv, Ye Chen, Fangting Li
المصدر: BMC Systems Biology
بيانات النشر: Springer Nature
مصطلحات موضوعية: Transcriptional Activation, Energy landscape, Gene regulatory network, Biology, Positive feedback, Stability (probability), Switching time, Structural Biology, Modelling and Simulation, Rare events, Molecular Biology, Feedback, Physiological, Genetics, Regulation of gene expression, Stochastic Processes, Models, Genetic, Stochastic process, Applied Mathematics, Ode, Computer Science Applications, Flow cytometry experiment, Kinetics, Phenotype, Modeling and Simulation, Gene expression, Biological system, Research Article
الوصف: Background Stochastic genetic switching driven by intrinsic noise is an important process in gene expression. When the rates of gene activation/inactivation are relatively slow, fast, or medium compared with the synthesis/degradation rates of mRNAs and proteins, the variability of protein and mRNA levels may exhibit very different dynamical patterns. It is desirable to provide a systematic approach to identify their key dynamical features in different regimes, aiming at distinguishing which regime a considered gene regulatory network is in from their phenotypic variations. Results We studied a gene expression model with positive feedbacks when genetic switching rates vary over a wide range. With the goal of providing a method to distinguish the regime of the switching rates, we first focus on understanding the essential dynamics of gene expression system in different cases. In the regime of slow switching rates, we found that the effective dynamics can be reduced to independent evolutions on two separate layers corresponding to gene activation and inactivation states, and the transitions between two layers are rare events, after which the system goes mainly along deterministic ODE trajectories on a particular layer to reach new steady states. The energy landscape in this regime can be well approximated by using Gaussian mixture model. In the regime of intermediate switching rates, we analyzed the mean switching time to investigate the stability of the system in different parameter ranges. We also discussed the case of fast switching rates from the viewpoint of transition state theory. Based on the obtained results, we made a proposal to distinguish these three regimes in a simulation experiment. We identified the intermediate regime from the fact that the strength of cellular memory is lower than the other two cases, and the fast and slow regimes can be distinguished by their different perturbation-response behavior with respect to the switching rates perturbations. Conclusions We proposed a simulation experiment to distinguish the slow, intermediate and fast regimes, which is the main point of our paper. In order to achieve this goal, we systematically studied the essential dynamics of gene expression system when the switching rates are in different regimes. Our theoretical understanding provides new insights on the gene expression experiments. Electronic supplementary material The online version of this article (doi:10.1186/s12918-015-0172-0) contains supplementary material, which is available to authorized users.
اللغة: English
تدمد: 1752-0509
DOI: 10.1186/s12918-015-0172-0
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f815ce66a4001e7127d3dda40e45c7aTest
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....3f815ce66a4001e7127d3dda40e45c7a
قاعدة البيانات: OpenAIRE
الوصف
تدمد:17520509
DOI:10.1186/s12918-015-0172-0