Gene expression is intrinsically noisy. Experimental studies have shown that random fluctuations are large bursts and heavytailed distributions. Therefore, this study aims to consider transition dynamics in a gene tra...Gene expression is intrinsically noisy. Experimental studies have shown that random fluctuations are large bursts and heavytailed distributions. Therefore, this study aims to consider transition dynamics in a gene transcriptional regulatory system via the mean first exit time(MFET) and first escape probability(FEP), when the degradation rate is under multiplicative non-Gaussian Lévy fluctuations in the sense of It? and Marcus forms. We find that, in the Marcus form case, the FEP corresponding to different stability index and noise intensity has an intersection point, whereas in the It? form case, the turning point only occurs at stability index. Increasing the initial CI concentration is helpful for improving the likelihood of transcription in both cases. Our results also imply that larger jumps of Lévy noise and smaller noise intensity can shorten the time of state transition to boost protein production.展开更多
Mammals have evolved mechanisms to sense hypoxia and induce hypoxic responses.Recently,high-throughput techniques have greatly promoted global studies of protein expression changes during hypoxia and the identificatio...Mammals have evolved mechanisms to sense hypoxia and induce hypoxic responses.Recently,high-throughput techniques have greatly promoted global studies of protein expression changes during hypoxia and the identification of candidate genes associated with hypoxiaadaptive evolution,which have contributed to the understanding of the complex regulatory networks of hypoxia.In this study,we developed an integrated resource for the expression dynamics of proteins in response to hypoxia(iHypoxia),and this database contains 2589 expression events of 1944 proteins identified by low-throughput experiments(LTEs)and 422,553 quantitative expression events of 33,559 proteins identified by high-throughput experiments from five mammals that exhibit a response to hypoxia.Various experimental details,such as the hypoxic experimental conditions,expression patterns,and sample types,were carefully collected and integrated.Furthermore,8788 candidate genes from diverse species inhabiting low-oxygen environments were also integrated.In addition,we conducted an orthologous search and computationally identified 394,141 proteins that may respond to hypoxia among 48 animals.An enrichment analysis of human proteins identified from LTEs shows that these proteins are enriched in certain drug targets and cancer genes.Annotation of known posttranslational modification(PTM)sites in the proteins identified by LTEs reveals that these proteins undergo extensive PTMs,particularly phosphorylation,ubiquitination,and acetylation.iHypoxia provides a convenient and user-friendly method for users to obtain hypoxia-related information of interest.展开更多
We present an algorithm for the stochastic simulation of gene expression and heterogeneous population dynamics.The algorithm combines an exact method to simulate molecular-level fluctuations in single cells and a cons...We present an algorithm for the stochastic simulation of gene expression and heterogeneous population dynamics.The algorithm combines an exact method to simulate molecular-level fluctuations in single cells and a constant-number Monte Carlo method to simulate time-dependent statistical characteristics of growing cell populations.To benchmark performance,we compare simulation results with steadystate and time-dependent analytical solutions for several scenarios,including steadystate and time-dependent gene expression,and the effects on population heterogeneity of cell growth,division,and DNA replication.This comparison demonstrates that the algorithm provides an efficient and accurate approach to simulate how complex biological features influence gene expression.We also use the algorithm to model gene expression dynamics within"bet-hedging"cell populations during their adaption to environmental stress.These simulations indicate that the algorithm provides a framework suitable for simulating and analyzing realistic models of heterogeneous population dynamics combining molecular-level stochastic reaction kinetics,relevant physiological details and phenotypic variability.展开更多
We present an accelerated method for stochastically simulating the dynamics of heterogeneous cell populations.The algorithm combines a Monte Carlo approach for simulating the biochemical kinetics in single cells with ...We present an accelerated method for stochastically simulating the dynamics of heterogeneous cell populations.The algorithm combines a Monte Carlo approach for simulating the biochemical kinetics in single cells with a constant-number Monte Carlo method for simulating the reproductive fitness and the statistical characteristics of growing cell populations.To benchmark accuracy and performance,we compare simulation results with those generated from a previously validated population dynamics algorithm.The comparison demonstrates that the accelerated method accurately simulates population dynamics with significant reductions in runtime under commonly invoked steady-state and symmetric cell division assumptions.Considering the increasing complexity of cell population models,the method is an important addition to the arsenal of existing algorithms for simulating cellular and population dynamics that enables efficient,coarse-grained exploration of parameter space.展开更多
How to accurately characterize the lift force on the particles near the solid surfaces is an ongoing challenge in fluid mechanics and microfluidic techniques, especially in a complex system with viscoelastic fluid or/...How to accurately characterize the lift force on the particles near the solid surfaces is an ongoing challenge in fluid mechanics and microfluidic techniques, especially in a complex system with viscoelastic fluid or/and soft surface that is commonly encountered in a biological system. The motions of the particles in vicinity of a surface can be simplified to be a rigid cylinder surrounded by the viscoelastic fluid moving along a substrate which can be rigid or soft according to different cases. In such an inertial free system with a wide range of Weissenberg number (Wi < 5.00, representing the ratio of the elastic force to the viscous force), firstly we numerically evaluate the influence of the systematic parameters, including the polymer viscosity, the geometry and Wi, on the net normal force for a cylinder closely moving along a rigid substrate, and the elasticity-induced lift force in a scaled form. It is shown that a strong shear arises in the viscoelastic confinement between the moving cylinder and the rigid substrate, it leads to the asymmetry of the first normal stress distribution around the cylinder, and thus the lift force. Then, the influence of a soft substrate on the lift force is considered, and we find that the lift force induced by the viscoelastic fluid always dominates in magnitude over that induced by the soft substrate deformation. This work provides a reliable scaling that can be utilized to quantify the elasticity-induced lift force on the particles in a viscoelastic system, such as the micro- and nanofluidic systems in biological applications.展开更多
Temperature influences the distribution, range, and phenology of plants. The key transcriptional activators of heat shock response in eukaryotes, the heat shock factors (HSFs), have undergone large-scale gene amplif...Temperature influences the distribution, range, and phenology of plants. The key transcriptional activators of heat shock response in eukaryotes, the heat shock factors (HSFs), have undergone large-scale gene amplification in plants. While HSFs are central in heat stress responses, their role in the response to ambient temperature changes is less well understood. We show here that the warm ambient temperature transcriptome is dependent upon the HSFA1 clade ofArabidopsis HSFs, which cause a rapid and dynamic eviction of H2A.Z nucleosomes at target genes. A transcriptional cascade results in the activation of multiple downstream stress-responsive transcription factors, triggering large-scale changes to the transcriptome in response to elevated temperature. H2A.Z nucleosomes are enriched at temperature-responsive genes at non-inducible temperature, and thus likely confer inducibility of gene expression and higher responsive dynamics. We propose that the antagonistic effects of H2A.Z and HSF1 provide a mechanism to activate gene expression rapidly and precisely in response to temperature, while preventing leaky transcription in the absence of an activation signal.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos. 12072261 and 11872305)the Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University (Grant No. CX2022069)。
文摘Gene expression is intrinsically noisy. Experimental studies have shown that random fluctuations are large bursts and heavytailed distributions. Therefore, this study aims to consider transition dynamics in a gene transcriptional regulatory system via the mean first exit time(MFET) and first escape probability(FEP), when the degradation rate is under multiplicative non-Gaussian Lévy fluctuations in the sense of It? and Marcus forms. We find that, in the Marcus form case, the FEP corresponding to different stability index and noise intensity has an intersection point, whereas in the It? form case, the turning point only occurs at stability index. Increasing the initial CI concentration is helpful for improving the likelihood of transcription in both cases. Our results also imply that larger jumps of Lévy noise and smaller noise intensity can shorten the time of state transition to boost protein production.
基金supported by grants from the National Key R&D Program of China(Grant No.2021YFA1302100 to Ze-Xian Liu)the National Natural Science Foundation of China(Grant No.U2004152 to Zhenlong Wang,Grant Nos.81972239 and 91953123 to Ze-Xian Liu)+2 种基金the Fostering Fund of Fundamental Research for Young Teachers of Zhengzhou University,China(Grant No.JC21343016 to Han Cheng)the Program for Guangdong Introducing Innovative and Entrepreneurial Teams,China(Grant No.2017ZT07S096 to Ze-Xian Liu)the Tip-Top Scientific and Technical Innovative Youth Talents of Guangdong Special Support Program,China(Grant No.2019TQ05Y351 to Ze-Xian Liu).
文摘Mammals have evolved mechanisms to sense hypoxia and induce hypoxic responses.Recently,high-throughput techniques have greatly promoted global studies of protein expression changes during hypoxia and the identification of candidate genes associated with hypoxiaadaptive evolution,which have contributed to the understanding of the complex regulatory networks of hypoxia.In this study,we developed an integrated resource for the expression dynamics of proteins in response to hypoxia(iHypoxia),and this database contains 2589 expression events of 1944 proteins identified by low-throughput experiments(LTEs)and 422,553 quantitative expression events of 33,559 proteins identified by high-throughput experiments from five mammals that exhibit a response to hypoxia.Various experimental details,such as the hypoxic experimental conditions,expression patterns,and sample types,were carefully collected and integrated.Furthermore,8788 candidate genes from diverse species inhabiting low-oxygen environments were also integrated.In addition,we conducted an orthologous search and computationally identified 394,141 proteins that may respond to hypoxia among 48 animals.An enrichment analysis of human proteins identified from LTEs shows that these proteins are enriched in certain drug targets and cancer genes.Annotation of known posttranslational modification(PTM)sites in the proteins identified by LTEs reveals that these proteins undergo extensive PTMs,particularly phosphorylation,ubiquitination,and acetylation.iHypoxia provides a convenient and user-friendly method for users to obtain hypoxia-related information of interest.
基金the National Science and Engineering Research Council of Canada(NSERC)the Canadian Institutes of Health Research(CIHR)+1 种基金the Academy of Finland(Application Number 129657,Finnish Programme for Centres of Excellence in Research 2006-2011,and 124615)the Tampere Graduate School in Information Science and Engineering(TISE).
文摘We present an algorithm for the stochastic simulation of gene expression and heterogeneous population dynamics.The algorithm combines an exact method to simulate molecular-level fluctuations in single cells and a constant-number Monte Carlo method to simulate time-dependent statistical characteristics of growing cell populations.To benchmark performance,we compare simulation results with steadystate and time-dependent analytical solutions for several scenarios,including steadystate and time-dependent gene expression,and the effects on population heterogeneity of cell growth,division,and DNA replication.This comparison demonstrates that the algorithm provides an efficient and accurate approach to simulate how complex biological features influence gene expression.We also use the algorithm to model gene expression dynamics within"bet-hedging"cell populations during their adaption to environmental stress.These simulations indicate that the algorithm provides a framework suitable for simulating and analyzing realistic models of heterogeneous population dynamics combining molecular-level stochastic reaction kinetics,relevant physiological details and phenotypic variability.
基金supported financially by the National Science and Engineering Research Council of Canada(NSERC).
文摘We present an accelerated method for stochastically simulating the dynamics of heterogeneous cell populations.The algorithm combines a Monte Carlo approach for simulating the biochemical kinetics in single cells with a constant-number Monte Carlo method for simulating the reproductive fitness and the statistical characteristics of growing cell populations.To benchmark accuracy and performance,we compare simulation results with those generated from a previously validated population dynamics algorithm.The comparison demonstrates that the accelerated method accurately simulates population dynamics with significant reductions in runtime under commonly invoked steady-state and symmetric cell division assumptions.Considering the increasing complexity of cell population models,the method is an important addition to the arsenal of existing algorithms for simulating cellular and population dynamics that enables efficient,coarse-grained exploration of parameter space.
基金the National Natural Science Foundation of China(Grant No.51875039).
文摘How to accurately characterize the lift force on the particles near the solid surfaces is an ongoing challenge in fluid mechanics and microfluidic techniques, especially in a complex system with viscoelastic fluid or/and soft surface that is commonly encountered in a biological system. The motions of the particles in vicinity of a surface can be simplified to be a rigid cylinder surrounded by the viscoelastic fluid moving along a substrate which can be rigid or soft according to different cases. In such an inertial free system with a wide range of Weissenberg number (Wi < 5.00, representing the ratio of the elastic force to the viscous force), firstly we numerically evaluate the influence of the systematic parameters, including the polymer viscosity, the geometry and Wi, on the net normal force for a cylinder closely moving along a rigid substrate, and the elasticity-induced lift force in a scaled form. It is shown that a strong shear arises in the viscoelastic confinement between the moving cylinder and the rigid substrate, it leads to the asymmetry of the first normal stress distribution around the cylinder, and thus the lift force. Then, the influence of a soft substrate on the lift force is considered, and we find that the lift force induced by the viscoelastic fluid always dominates in magnitude over that induced by the soft substrate deformation. This work provides a reliable scaling that can be utilized to quantify the elasticity-induced lift force on the particles in a viscoelastic system, such as the micro- and nanofluidic systems in biological applications.
文摘Temperature influences the distribution, range, and phenology of plants. The key transcriptional activators of heat shock response in eukaryotes, the heat shock factors (HSFs), have undergone large-scale gene amplification in plants. While HSFs are central in heat stress responses, their role in the response to ambient temperature changes is less well understood. We show here that the warm ambient temperature transcriptome is dependent upon the HSFA1 clade ofArabidopsis HSFs, which cause a rapid and dynamic eviction of H2A.Z nucleosomes at target genes. A transcriptional cascade results in the activation of multiple downstream stress-responsive transcription factors, triggering large-scale changes to the transcriptome in response to elevated temperature. H2A.Z nucleosomes are enriched at temperature-responsive genes at non-inducible temperature, and thus likely confer inducibility of gene expression and higher responsive dynamics. We propose that the antagonistic effects of H2A.Z and HSF1 provide a mechanism to activate gene expression rapidly and precisely in response to temperature, while preventing leaky transcription in the absence of an activation signal.