Gillespie's Stochastic Algorithm Research Articles

Modeling and simulation of cell migration on the basis of force equilibrium.

To study cell behavior, we developed a cell model to simulate cell movements and the interacting forces among cells and between cells and obstacles. The developed model simulates several cells simultaneously and examines correlations among characteristic parameters between cells and substrates during migration. We modified Odde's model to develop fundamental model, applied Gillespie's stochastic algorithm to design time during in the migration simulation, and employed Keren's membrane theory to analyze the equilibrium at the leading edges. Thus, the proposed model can analyze stresses due to substrate, the intracellular body, and the external interaction between cells and obstacles. Simulation results indicate that cell-cell interaction depends on the equilibrium between the forces at the leading edge of the membrane, namely the cell-substrate interaction force, cell-cell interaction forces, and the cell membrane force. These results also indicate that the migration direction is dependent on the resultant forces. The membrane force and substrate force directions are "low correlation," and the polymerization rate exhibits "little correlative" with the migration direction. We propose a modified cell migration model for simulating allocation and interaction among multiple cells. This model helps indicate the weightings of characteristic parameters that affect the cell migration direction and velocity.

Stochastic Kinetic Treatment of Protein Aggregation and the Effects of Macromolecular Crowding.

Investigation of protein self-assembly processes is important for understanding the growth processes of functional proteins as well as disease-causing amyloids. Inside cells, intrinsic molecular fluctuations are so high that they cast doubt on the validity of the deterministic rate-equation approach. Furthermore, the protein environments inside cells are often crowded with other macromolecules, with volume fractions of the crowders as high as 40%. We have developed a stochastic kinetic framework using Gillespie's algorithm for general systems undergoing particle self-assembly, including particularly protein aggregation at the cellular level. The effects of macromolecular crowding are investigated using models built on scaled-particle and transition-state theories. The stochastic kinetic method can be formulated to provide information on the dominating aggregation mechanisms in a method called reaction frequency (or propensity) analysis. This method reveals that the change of scaling laws related to the lag time can be directly related to the change in the frequencies of reaction mechanisms. Further examination of the time evolution of the fibril mass and length quantities unveils that maximal fluctuations occur in the periods of rapid fibril growth and the fluctuations of both quantities can be sensitive functions of rate constants. The presence of crowders often amplifies the roles of primary and secondary nucleation and causes shifting in the relative importance of elongation, shrinking, fragmentation, and coagulation of linear aggregates. We also show a dual effect of changing volume on the halftime of aggregation for ApoC2 which is reduced in the presence of crowders. A comparison of the results of stochastic simulations with those of rate equations gives us information on the convergence relation between them and how the roles of reaction mechanisms change as the system volume is varied.

Coevolutionary dynamics of a variant of the cyclic Lotka–Volterra model with three-agent interactions

We study a variant of the cyclic Lotka-Volterra model with three-agent interactions. Inspired by a multiplayer variation of the Rock-Paper-Scissors game, the model describes an ideal ecosystem in which cyclic competition among three species develops through cooperative predation. Its rate equations in a well-mixed environment display a degenerate Hopf bifurcation, occurring as reactions involving two predators plus one prey have the same rate as reactions involving two preys plus one predator. We estimate the magnitude of the stochastic noise at the bifurcation point, where finite size effects turn neutrally stable orbits into erratically diverging trajectories. In particular, we compare analytic predictions for the extinction probability, derived in the Fokker-Planck approximation, with numerical simulations based on the Gillespie stochastic algorithm. We then extend the analysis of the phase portrait to heterogeneous rates. In a well-mixed environment, we observe a continuum of degenerate Hopf bifurcations, generalizing the above one. Neutral stability ensues from a complex equilibrium between different reactions. Remarkably, on a two-dimensional lattice, all bifurcations disappear as a consequence of the spatial locality of the interactions. In the second part of the paper, we investigate the effects of mobility in a lattice metapopulation model with patches hosting several agents. We find that strategies propagate along the arms of rotating spirals, as they usually do in models of cyclic dominance. We observe propagation instabilities in the regime of large wavelengths. We also examine three-agent interactions inducing nonlinear diffusion.

Pandæsim: An Epidemic Spreading Stochastic Simulator.

Simple SummaryIn order to study the efficiency of countermeasures used against the Covid-19 pandemic at the scale of a country, we designed a model and developed an efficient simulation program based on a well known discrete stochastic simulation framework along with a standard, coarse grain, spatial localisation extension. Our particular approach allows us also to implement deterministic continuous resolutions of the same model. We applied it to the Covid-19 epidemic in France where lockdown countermeasures were used. With the stochastic discrete method, we found good correlations between the simulation results and the statistics gathered from hospitals. In contrast, the deterministic continuous approach lead to very different results. We proposed an explanation based on the fact that the effects of discretisation are high for small values, but low for large values. When we add stochasticity, it can explain the differences in behaviour of those two approaches. This system is one more tool to study different countermeasures to epidemics, from lockdowns to social distancing, and also the effects of mass vaccination. It could be improved by including the possibility of individual reinfection.Many methods have been used to model epidemic spreading. They include ordinary differential equation systems for globally homogeneous environments and partial differential equation systems to take into account spatial localisation and inhomogeneity. Stochastic differential equations systems have been used to model the inherent stochasticity of epidemic spreading processes. In our case study, we wanted to model the numbers of individuals in different states of the disease, and their locations in the country. Among the many existing methods we used our own variant of the well known Gillespie stochastic algorithm, along with the sub-volumes method to take into account the spatial localisation. Our algorithm allows us to easily switch from stochastic discrete simulation to continuous deterministic resolution using mean values. We applied our approaches on the study of the Covid-19 epidemic in France. The stochastic discrete version of Pandæsim showed very good correlations between the simulation results and the statistics gathered from hospitals, both on day by day and on global numbers, including the effects of the lockdown. Moreover, we have highlighted interesting differences in behaviour between the continuous and discrete methods that may arise in some particular conditions.

Fast and Precise Emulation of Stochastic Biochemical Reaction Networks With Amplified Thermal Noise in Silicon Chips.

The analysis and simulation of complex interacting biochemical reaction pathways in cells is important in all of systems biology and medicine. Yet, the dynamics of even a modest number of noisy or stochastic coupled biochemical reactions is extremely time consuming to simulate. In large part, this is because of the expensive cost of random number and Poisson process generation and the presence of stiff, coupled, nonlinear differential equations. Here, we demonstrate that we can amplify inherent thermal noise in chips to emulate randomness physically, thus alleviating these costs significantly. Concurrently, molecular flux in thermodynamic biochemical reactions maps to thermodynamic electronic current in a transistor such that stiff nonlinear biochemical differential equations are emulated exactly in compact, digitally programmable, highly parallel analog "cytomorphic" transistor circuits. For even small-scale systems involving just 80 stochastic reactions, our 0.35-μm BiCMOS chips yield a 311× speedup in the simulation time of Gillespie's stochastic algorithm over COPASI, a fast biochemical-reaction software simulator that is widely used in computational biology; they yield a 15500× speedup over equivalent MATLAB stochastic simulations. The chip emulation results are consistent with these software simulations over a large range of signal-to-noise ratios. Most importantly, our physical emulation of Poisson chemical dynamics does not involve any inherently sequential processes and updates such that, unlike prior exact simulation approaches, they are parallelizable, asynchronous, and enable even more speedup for larger-size networks.

Modeling Langmuir isotherms with the Gillespie stochastic algorithm

The overall goal of this work is to develop a robust modeling approach that is capable of simulating single and multicomponent isotherms for biological molecules interacting with a variety of adsorbents. Provided the ratio between the forward and reverse adsorption/desorption constants is known, the Gillespie stochastic algorithm has been shown to be effective in modeling isotherms consistent with the Langmuir theory and uptake curves that fall outside this traditional approach. We have used this method to model protein adsorption on ion-exchange adsorbents, hydrophobic interactive adsorbents and ice crystals. In our latest efforts we have applied the Gillespie approach to simulate binary and ternary isotherms from the literature involving gas–solid adsorption applications. In each case the model is consistent with the experimental results presented.