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Search Results: 1 - 10 of 133071 matches for " Rahul V. Kulkarni "
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On the structural properties of small-world networks with finite range of shortcut links
Tao Jia,Rahul V. Kulkarni
Computer Science , 2011,
Abstract: We explore a new variant of Small-World Networks (SWNs), in which an additional parameter ($r$) sets the length scale over which shortcuts are uniformly distributed. When $r=0$ we have an ordered network, whereas $r=1$ corresponds to the original SWN model. These short-range SWNs have a similar degree distribution and scaling properties as the original SWN model. We observe the small-world phenomenon for $r \ll 1$ indicating that global shortcuts are not necessary for the small-world effect. For short-range SWNs, the average path length changes nonmonotonically with system size, whereas for the original SWN model it increases monotonically. We propose an expression for the average path length for short-range SWNs based on numerical simulations and analytical approximations.
Post-transcriptional regulation of noise in protein distributions during gene expression
Tao Jia,Rahul V. Kulkarni
Quantitative Biology , 2010, DOI: 10.1103/PhysRevLett.105.018101
Abstract: The intrinsic stochasticity of gene expression can lead to large variability of protein levels across a population of cells. Variability (or noise) in protein distributions can be modulated by cellular mechanisms of gene regulation; in particular, there is considerable interest in understanding the role of post-transcriptional regulation. To address this issue, we propose and analyze a stochastic model for post-transcriptional regulation of gene expression. The analytical solution of the model provides insight into the effects of different mechanisms of post-transcriptional regulation on the noise in protein distributions. The results obtained also demonstrate how different sources of intrinsic noise in gene expression can be discriminated based on observations of regulated protein distributions.
Intrinsic noise in stochastic models of gene expression with molecular memory and bursting
Tao Jia,Rahul V. Kulkarni
Quantitative Biology , 2011, DOI: 10.1103/PhysRevLett.106.058102
Abstract: Regulation of intrinsic noise in gene expression is essential for many cellular functions. Correspondingly, there is considerable interest in understanding how different molecular mechanisms of gene expression impact variations in protein levels across a population of cells. In this work, we analyze a stochastic model of bursty gene expression which considers general waiting-time distributions governing arrival and decay of proteins. By mapping the system to models analyzed in queueing theory, we derive analytical expressions for the noise in steady-state protein distributions. The derived results extend previous work by including the effects of arbitrary probability distributions representing the effects of molecular memory and bursting. The analytical expressions obtained provide insight into the role of transcriptional, post-transcriptional and post-translational mechanisms in controlling the noise in gene expression.
Transcriptional bursting in gene expression: analytical results for general stochastic models
Niraj Kumar,Abhyudai Singh,Rahul V. Kulkarni
Physics , 2014,
Abstract: Gene expression in individual cells is highly variable and sporadic, often resulting in the synthesis of mRNAs and proteins in bursts. Bursting in gene expression is known to impact cell-fate in diverse systems ranging from latency in HIV-1 viral infections to cellular differentiation. It is generally assumed that bursts are geometrically distributed and that they arrive according to a Poisson process. On the other hand, recent single-cell experiments provide evidence for complex burst arrival processes, highlighting the need for more general stochastic models. To address this issue, we invoke a mapping between general models of gene expression and systems studied in queueing theory to derive exact analytical expressions for the moments associated with mRNA/protein steady-state distributions. These moments are then used to derive explicit conditions, based entirely on experimentally measurable quantities, that determine if the burst distributions deviate from the geometric distribution or if burst arrival deviates from a Poisson process. For non-Poisson arrivals, we develop approaches for accurate estimation of burst parameters.
Exact distributions for stochastic gene expression models with bursting and feedback
Niraj Kumar,Thierry Platini,Rahul V. Kulkarni
Physics , 2014, DOI: 10.1103/PhysRevLett.113.268105
Abstract: Stochasticity in gene expression can give rise to fluctuations in protein levels and lead to phenotypic variation across a population of genetically identical cells. Recent experiments indicate that bursting and feedback mechanisms play important roles in controlling noise in gene expression and phenotypic variation. A quantitative understanding of the impact of these factors requires analysis of the corresponding stochastic models. However, for stochastic models of gene expression with feedback and bursting, exact analytical results for protein distributions have not been obtained so far. Here, we analyze a model of gene expression with bursting and feedback regulation and obtain exact results for the corresponding protein steady-state distribution. The results obtained provide new insights into the role of bursting and feedback in noise regulation and optimization. Furthermore, for a specific choice of parameters, the system studied maps on to a two-state biochemical switch driven by a bursty input noise source. The analytical results derived thus provide quantitative insights into diverse cellular processes involving noise in gene expression and biochemical switching.
Regulation by small RNAs via coupled degradation: mean-field and variational approaches
Thierry Platini,Tao Jia,Rahul V. Kulkarni
Quantitative Biology , 2011, DOI: 10.1103/PhysRevE.84.021928
Abstract: Regulatory genes called small RNAs (sRNAs) are known to play critical roles in cellular responses to changing environments. For several sRNAs, regulation is effected by coupled stoichiometric degradation with messenger RNAs (mRNAs). The nonlinearity inherent in this regulatory scheme indicates that exact analytical solutions for the corresponding stochastic models are intractable. Here, we present a variational approach to analyze a well-studied stochastic model for regulation by sRNAs via coupled degradation. The proposed approach is efficient and provides accurate estimates of mean mRNA levels as well as higher order terms. Results from the variational ansatz are in excellent agreement with data from stochastic simulations for a wide range of parameters, including regions of parameter space where mean-field approaches break down. The proposed approach can be applied to quantitatively model stochastic gene expression in complex regulatory networks.
Stochastic modeling of regulation of gene expression by multiple small RNAs
Charles Baker,Tao Jia,Rahul V. Kulkarni
Quantitative Biology , 2011, DOI: 10.1103/PhysRevE.85.061915
Abstract: A wealth of new research has highlighted the critical roles of small RNAs (sRNAs) in diverse processes such as quorum sensing and cellular responses to stress. The pathways controlling these processes often have a central motif comprising of a master regulator protein whose expression is controlled by multiple sRNAs. However, the regulation of stochastic gene expression of a single target gene by multiple sRNAs is currently not well understood. To address this issue, we analyze a stochastic model of regulation of gene expression by multiple sRNAs. For this model, we derive exact analytic results for the regulated protein distribution including compact expressions for its mean and variance. The derived results provide novel insights into the roles of multiple sRNAs in fine-tuning the noise in gene expression. In particular, we show that, in contrast to regulation by a single sRNA, multiple sRNAs provide a mechanism for independently controlling the mean and variance of the regulated protein distribution.
Exact protein distributions for stochastic models of gene expression using partitioning of Poisson processes
Hodjat Pendar,Thierry Platini,Rahul V. Kulkarni
Quantitative Biology , 2013, DOI: 10.1103/PhysRevE.87.042720
Abstract: Stochasticity in gene expression gives rise to fluctuations in protein levels across a population of genetically identical cells. Such fluctuations can lead to phenotypic variation in clonal populations, hence there is considerable interest in quantifying noise in gene expression using stochastic models. However, obtaining exact analytical results for protein distributions has been an intractable task for all but the simplest models. Here, we invoke the partitioning property of Poisson processes to develop a mapping that significantly simplifies the analysis of stochastic models of gene expression. The mapping leads to exact protein distributions using results for mRNA distributions in models with promoter-based regulation. Using this approach, we derive exact analytical results for steady-state and time-dependent distributions for the basic 2-stage model of gene expression. Furthermore, we show how the mapping leads to exact protein distributions for extensions of the basic model that include the effects of post-transcriptional and post-translational regulation. The approach developed in this work is widely applicable and can contribute to a quantitative understanding of stochasticity in gene expression and its regulation.
Applications of Little's Law to stochastic models of gene expression
Vlad Elgart,Tao Jia,Rahul V. Kulkarni
Quantitative Biology , 2010, DOI: 10.1103/PhysRevE.82.021901
Abstract: The intrinsic stochasticity of gene expression can lead to large variations in protein levels across a population of cells. To explain this variability, different sources of mRNA fluctuations ('Poisson' and 'Telegraph' processes) have been proposed in stochastic models of gene expression. Both Poisson and Telegraph scenario models explain experimental observations of noise in protein levels in terms of 'bursts' of protein expression. Correspondingly, there is considerable interest in establishing relations between burst and steady-state protein distributions for general stochastic models of gene expression. In this work, we address this issue by considering a mapping between stochastic models of gene expression and problems of interest in queueing theory. By applying a general theorem from queueing theory, Little's Law, we derive exact relations which connect burst and steady-state distribution means for models with arbitrary waiting-time distributions for arrival and degradation of mRNAs and proteins. The derived relations have implications for approaches to quantify the degree of transcriptional bursting and hence to discriminate between different sources of intrinsic noise in gene expression. To illustrate this, we consider a model for regulation of protein expression bursts by small RNAs. For a broad range of parameters, we derive analytical expressions (validated by stochastic simulations) for the mean protein levels as the levels of regulatory small RNAs are varied. The results obtained show that the degree of transcriptional bursting can, in principle, be determined from changes in mean steady-state protein levels for general stochastic models of gene expression.
Connecting protein and mRNA burst distributions for stochastic models of gene expression
Vlad Elgart,Tao Jia,Andrew T. Fenley,Rahul V. Kulkarni
Physics , 2011, DOI: 10.1088/1478-3975/8/4/046001
Abstract: The intrinsic stochasticity of gene expression can lead to large variability in protein levels for genetically identical cells. Such variability in protein levels can arise from infrequent synthesis of mRNAs which in turn give rise to bursts of protein expression. Protein expression occurring in bursts has indeed been observed experimentally and recent studies have also found evidence for transcriptional bursting, i.e. production of mRNAs in bursts. Given that there are distinct experimental techniques for quantifying the noise at different stages of gene expression, it is of interest to derive analytical results connecting experimental observations at different levels. In this work, we consider stochastic models of gene expression for which mRNA and protein production occurs in independent bursts. For such models, we derive analytical expressions connecting protein and mRNA burst distributions which show how the functional form of the mRNA burst distribution can be inferred from the protein burst distribution. Additionally, if gene expression is repressed such that observed protein bursts arise only from single mRNAs, we show how observations of protein burst distributions (repressed and unrepressed) can be used to completely determine the mRNA burst distribution. Assuming independent contributions from individual bursts, we derive analytical expressions connecting means and variances for burst and steady-state protein distributions. Finally, we validate our general analytical results by considering a specific reaction scheme involving regulation of protein bursts by small RNAs. For a range of parameters, we derive analytical expressions for regulated protein distributions that are validated using stochastic simulations. The analytical results obtained in this work can thus serve as useful inputs for a broad range of studies focusing on stochasticity in gene expression.
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