scholarly journals Cluster mean-field theory accurately predicts statistical properties of large-scale DNA methylation patterns

2021 ◽  
Author(s):  
Lyndsay Kerr ◽  
Duncan Sproul ◽  
Ramon Grima

The accurate establishment and maintenance of DNA methylation patterns is vital for mammalian development and disruption to these processes causes human disease. Our understanding of DNA methylation mechanisms has been facilitated by mathematical modelling, particularly stochastic simulations. Mega-base scale variation in DNA methylation patterns is observed in development, cancer and ageing and the mechanisms generating these patterns are little understood. However, the computational cost of stochastic simulations prevents them from modelling such large genomic regions. Here we test the utility of three different mean-field models to predict large-scale DNA methylation patterns. By comparison to stochastic simulations, we show that a cluster mean-field model accurately predicts the statistical properties of steady-state DNA methylation patterns, including the mean and variance of methylation levels calculated across a system of CpG sites, as well as the covariance and correlation of methylation levels between neighbouring sites. We also demonstrate that a cluster mean-field model can be used within an approximate Bayesian computation framework to accurately infer model parameters from data. As mean-field models can be solved numerically in a few seconds, our work demonstrates their utility for understanding the processes underpinning large-scale DNA methylation patterns.

2018 ◽  
Author(s):  
Matteo di Volo ◽  
Alberto Romagnoni ◽  
Cristiano Capone ◽  
Alain Destexhe

AbstractAccurate population models are needed to build very large scale neural models, but their derivation is difficult for realistic networks of neurons, in particular when nonlinear properties are involved such as conductance-based interactions and spike-frequency adaptation. Here, we consider such models based on networks of Adaptive exponential Integrate and fire excitatory and inhibitory neurons. Using a Master Equation formalism, we derive a mean-field model of such networks and compare it to the full network dynamics. The mean-field model is capable to correctly predict the average spontaneous activity levels in asynchronous irregular regimes similar to in vivo activity. It also captures the transient temporal response of the network to complex external inputs. Finally, the mean-field model is also able to quantitatively describe regimes where high and low activity states alternate (UP-DOWN state dynamics), leading to slow oscillations. We conclude that such mean-field models are “biologically realistic” in the sense that they can capture both spontaneous and evoked activity, and they naturally appear as candidates to build very large scale models involving multiple brain areas.


2019 ◽  
Vol 31 (4) ◽  
pp. 653-680 ◽  
Author(s):  
Matteo di Volo ◽  
Alberto Romagnoni ◽  
Cristiano Capone ◽  
Alain Destexhe

Accurate population models are needed to build very large-scale neural models, but their derivation is difficult for realistic networks of neurons, in particular when nonlinear properties are involved, such as conductance-based interactions and spike-frequency adaptation. Here, we consider such models based on networks of adaptive exponential integrate-and-fire excitatory and inhibitory neurons. Using a master equation formalism, we derive a mean-field model of such networks and compare it to the full network dynamics. The mean-field model is capable of correctly predicting the average spontaneous activity levels in asynchronous irregular regimes similar to in vivo activity. It also captures the transient temporal response of the network to complex external inputs. Finally, the mean-field model is also able to quantitatively describe regimes where high- and low-activity states alternate (up-down state dynamics), leading to slow oscillations. We conclude that such mean-field models are biologically realistic in the sense that they can capture both spontaneous and evoked activity, and they naturally appear as candidates to build very large-scale models involving multiple brain areas.


2021 ◽  
Vol 4 (2) ◽  
Author(s):  
Corrado Rainone ◽  
Pierfrancesco Urbani ◽  
Francesco Zamponi ◽  
Edan Lerner ◽  
Eran Bouchbinder

Structural glasses feature quasilocalized excitations whose frequencies \omegaω follow a universal density of states {D}(\omega)\!\sim\!\omega^4D(ω)∼ω4. Yet, the underlying physics behind this universality is not fully understood. Here we study a mean-field model of quasilocalized excitations in glasses, viewed as groups of particles embedded inside an elastic medium and described collectively as anharmonic oscillators. The oscillators, whose harmonic stiffness is taken from a rather featureless probability distribution (of upper cutoff \kappa_0κ0) in the absence of interactions, interact among themselves through random couplings (characterized by a strength JJ) and with the surrounding elastic medium (an interaction characterized by a constant force hh). We first show that the model gives rise to a gapless density of states {D}(\omega)\!=\!A_{g}\,\omega^4D(ω)=Agω4 for a broad range of model parameters, expressed in terms of the strength of the oscillators’ stabilizing anharmonicity, which plays a decisive role in the model. Then — using scaling theory and numerical simulations — we provide a complete understanding of the non-universal prefactor A_{g}(h,J,\kappa_0)Ag(h,J,κ0), of the oscillators’ interaction-induced mean square displacement and of an emerging characteristic frequency, all in terms of properly identified dimensionless quantities. In particular, we show that A_{g}(h,J,\kappa_0)Ag(h,J,κ0) is a non-monotonic function of JJ for a fixed hh, varying predominantly exponentially with -(\kappa_0 h^{2/3}\!/J^2)−(κ0h2/3/J2) in the weak interactions (small JJ) regime — reminiscent of recent observations in computer glasses — and predominantly decays as a power-law for larger JJ, in a regime where hh plays no role. We discuss the physical interpretation of the model and its possible relations to available observations in structural glasses, along with delineating some future research directions.


Author(s):  
Nikki Sonenberg ◽  
Grzegorz Kielanski ◽  
Benny Van Houdt

Randomized work stealing is used in distributed systems to increase performance and improve resource utilization. In this article, we consider randomized work stealing in a large system of homogeneous processors where parent jobs spawn child jobs that can feasibly be executed in parallel with the parent job. We analyse the performance of two work stealing strategies: one where only child jobs can be transferred across servers and the other where parent jobs are transferred. We define a mean-field model to derive the response time distribution in a large-scale system with Poisson arrivals and exponential parent and child job durations. We prove that the model has a unique fixed point that corresponds to the steady state of a structured Markov chain, allowing us to use matrix analytic methods to compute the unique fixed point. The accuracy of the mean-field model is validated using simulation. Using numerical examples, we illustrate the effect of different probe rates, load, and different child job size distributions on performance with respect to the two stealing strategies, individually, and compared to each other.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Weijie Ye

Since the high dimension and complexity of the large-scale spiking neural network, it is difficult to research the network dynamics. In recent decades, the mean-field approximation has been a useful method to reduce the dimension of the network. In this study, we construct a large-scale spiking neural network with quadratic integrate-and-fire neurons and reduce it to a mean-field model to research the network dynamics. We find that the activity of the mean-field model is consistent with the network activity. Based on this agreement, a two-parameter bifurcation analysis is performed on the mean-field model to understand the network dynamics. The bifurcation scenario indicates that the network model has the quiescence state, the steady state with a relatively high firing rate, and the synchronization state which correspond to the stable node, stable focus, and stable limit cycle of the system, respectively. There exist several stable limit cycles with different periods, so we can observe the synchronization states with different periods. Additionally, the model shows bistability in some regions of the bifurcation diagram which suggests that two different activities coexist in the network. The mechanisms that how these states switch are also indicated by the bifurcation curves.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matteo Di Volo ◽  
Alain Destexhe

AbstractCerebral cortex is characterized by a strong neuron-to-neuron heterogeneity, but it is unclear what consequences this may have for cortical computations, while most computational models consider networks of identical units. Here, we study network models of spiking neurons endowed with heterogeneity, that we treat independently for excitatory and inhibitory neurons. We find that heterogeneous networks are generally more responsive, with an optimal responsiveness occurring for levels of heterogeneity found experimentally in different published datasets, for both excitatory and inhibitory neurons. To investigate the underlying mechanisms, we introduce a mean-field model of heterogeneous networks. This mean-field model captures optimal responsiveness and suggests that it is related to the stability of the spontaneous asynchronous state. The mean-field model also predicts that new dynamical states can emerge from heterogeneity, a prediction which is confirmed by network simulations. Finally we show that heterogeneous networks maximise the information flow in large-scale networks, through recurrent connections. We conclude that neuronal heterogeneity confers different responsiveness to neural networks, which should be taken into account to investigate their information processing capabilities.


2011 ◽  
Vol 25 (13) ◽  
pp. 1791-1806 ◽  
Author(s):  
H. YURTSEVEN ◽  
M. KURT

We study here the tilt angle and the temperature shifts as a function of concentration for the AC* phase transition in a binary mixture, using our mean field model with the biquadratic P2θ2 coupling — and also with the bilinear Pθ and P2θ2 couplings. By expanding the free energy in terms of the tilt angle and polarization, the tilt angle and the temperature shift are evaluated by using the coefficients given in the free energy expansion. By employing a concentration-dependent coefficient, the tilt angle and the temperature shift are calculated as a function of concentration of 10.O.4 for the SmAC* transition in a binary mixture of C7 and 10.O.4. Our calculated values of the tilt angle and the temperature shifts decrease as the concentration of 10.O.4 increases, as confirmed experimentally for the AC* transition in this binary mixture. This indicates that our mean field models studied here are satisfactory to explain the observed behavior of the AC* transition of the binary mixture of C7 and 10.O.4.


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