scholarly journals Inferring extrinsic noise from single-cell gene expression data using Approximate Bayesian Computation.

2015 ◽  
Author(s):  
Oleg Lenive ◽  
Paul DW Kirk ◽  
Michael PH Stumpf

Background: Gene expression is known to be an intrinsically stochastic process which can involve single-digit numbers of mRNA molecules in a cell at any given time. The modelling of such processes calls for the use of exact stochastic simulation methods, most notably the Gillespie algorithm. However, this stochasticity, also termed “intrinsic noise”, does not account for all the variability between genetically identical cells growing in a homogeneous environment. Despite substantial experimental efforts, determining appropriate model parameters continues to be a challenge. Methods based on approximate Bayesian computation can be used to obtain posterior parameter distributions given the observed data. However, such inference procedures require large numbers of simulations of the model and exact stochastic simulation is computationally costly. In this work we focus on the specific case of trying to infer model parameters describing reaction rates and extrinsic noise on the basis of measurements of molecule numbers in individual cells at a given time point. Results: To make the problem computationally tractable we develop an exact, model-specific, stochastic simulation algorithm for the commonly used two-state model of gene expression. This algorithm relies on certain assumptions and favourable properties of the model to forgo the simulation of the whole temporal trajectory of protein numbers in the system, instead returning only the number of protein and mRNA molecules present in the system at a specified time point. The computational gain is proportional to the number of protein molecules created in the system and becomes significant for systems involving hundreds or thousands of protein molecules. We employ this algorithm, approximate Bayesian computation, and published gene expression data for Escherichia coli to simultaneously infer the model's rate parameters and parameters describing extrinsic noise for 86 genes.

Sensors ◽  
2020 ◽  
Vol 20 (11) ◽  
pp. 3197 ◽  
Author(s):  
Zhouquan Feng ◽  
Yang Lin ◽  
Wenzan Wang ◽  
Xugang Hua ◽  
Zhengqing Chen

A novel probabilistic approach for model updating based on approximate Bayesian computation with subset simulation (ABC-SubSim) is proposed for damage assessment of structures using modal data. The ABC-SubSim is a likelihood-free Bayesian approach in which the explicit expression of likelihood function is avoided and the posterior samples of model parameters are obtained using the technique of subset simulation. The novel contributions of this paper are on three fronts: one is the introduction of some new stopping criteria to find an appropriate tolerance level for the metric used in the ABC-SubSim; the second one is the employment of a hybrid optimization scheme to find finer optimal values for the model parameters; and the last one is the adoption of an iterative approach to determine the optimal weighting factors related to the residuals of modal frequency and mode shape in the metric. The effectiveness of this approach is demonstrated using three illustrative examples.


2016 ◽  
Author(s):  
Robert J. H. Ross ◽  
R. E. Baker ◽  
Andrew Parker ◽  
M. J. Ford ◽  
R. L. Mort ◽  
...  

AbstractIn this work we implement approximate Bayesian computational methods to improve the design of a wound-healing assay used to quantify cell-cell interactions. This is important as cell-cell interactions, such as adhesion and repulsion, have been shown to play an important role in cell migration. Initially, we demonstrate with a model of an ideal experiment that we are able to identify model parameters for agent motility and adhesion, given we choose appropriate summary statistics. Following this, we replace our model of an ideal experiment with a model representative of a practically realisable experiment. We demonstrate that, given the current (and commonly used) experimental set-up, model parameters cannot be accurately identified using approximate Bayesian computation methods. We compare new experimental designs through simulation, and show more accurate identification of model parameters is possible by expanding the size of the domain upon which the experiment is performed, as opposed to increasing the number of experimental repeats. The results presented in this work therefore describe time and cost-saving alterations for a commonly performed experiment for identifying cell motility parameters. Moreover, the results presented in this work will be of interest to those concerned with performing experiments that allow for the accurate identification of parameters governing cell migratory processes, especially cell migratory processes in which cell-cell adhesion or repulsion are known to play a significant role.


2020 ◽  
Vol 5 ◽  
Author(s):  
Nikolai Bode

Simulation models for pedestrian crowds are a ubiquitous tool in research and industry. It is crucial that the parameters of these models are calibrated carefully and ultimately it will be of interest to compare competing models to decide which model is best suited for a particular purpose. In this contribution, I demonstrate how Approximate Bayesian Computation (ABC), which is already a popular tool in other areas of science, can be used for model fitting and model selection in a pedestrian dynamics context. I fit two different models for pedestrian dynamics to data on a crowd passing in one direction through a bottleneck. One model describes movement in continuous-space, the other model is a cellular automaton and thus describes movement in discrete-space. In addition, I compare models to data using two metrics. The first is based on egress times and the second on the velocity of pedestrians in front of the bottleneck. My results show that while model fitting is successful, a substantial degree of uncertainty about the value of some model parameters remains after model fitting. Importantly, the choice of metric in model fitting can influence parameter estimates. Model selection is inconclusive for the egress time metric but supports the continuous-space model for the velocity-based metric. These findings show that ABC is a flexible approach and highlights the difficulties associated with model fitting and model selection for pedestrian dynamics. ABC requires many simulation runs and choosing appropriate metrics for comparing data to simulations requires careful attention. Despite this, I suggest ABC is a promising tool, because it is versatile and easily implemented for the growing number of openly available crowd simulators and data sets.


2021 ◽  
Vol 8 (6) ◽  
pp. 202237
Author(s):  
Yunchen Xiao ◽  
Len Thomas ◽  
Mark A. J. Chaplain

We present two different methods to estimate parameters within a partial differential equation model of cancer invasion. The model describes the spatio-temporal evolution of three variables—tumour cell density, extracellular matrix density and matrix degrading enzyme concentration—in a one-dimensional tissue domain. The first method is a likelihood-free approach associated with approximate Bayesian computation; the second is a two-stage gradient matching method based on smoothing the data with a generalized additive model (GAM) and matching gradients from the GAM to those from the model. Both methods performed well on simulated data. To increase realism, additionally we tested the gradient matching scheme with simulated measurement error and found that the ability to estimate some model parameters deteriorated rapidly as measurement error increased.


Author(s):  
Anubhav Gupta ◽  
Owen Petchey

1) Food web models explain and predict the trophic interactions in a food web, and they can infer missing interactions among the organisms. The allometric diet breadth model (ADBM) is a food web model based on the foraging theory. In the ADBM the foraging parameters are allometrically scaled to body sizes of predators and prey. In Petchey et al. (2008), the parameterisation of the ADBM had two limitations: (a) the model parameters were point estimates, and (b) food web connectance was not estimated. 2) The novelty of our current approach is: (a) we consider multiple predictions from the ADBM by parameterising it with approximate Bayesian computation, to estimate parameter distributions and not point estimates. (b) Connectance emerges from the parameterisation, by measuring model fit using the true skill statistic, which takes into account prediction of both the presences and absences of links. 3) We fit the ADBM using approximate Bayesian computation to 16 observed food webs from a wide variety of ecosystems. Connectance was consistently overestimated in the new parameterisation method. In some of the food webs, considerable variation in estimated parameter distributions occurred, and resulted in considerable variation (i.e. uncertainty) in predicted food web structure. 4) We conclude that the observed food web data is likely missing some trophic links that do actually occur, and that the ADBM likely predicts some links that do not exist. The latter could be addressed by accounting in the ADBM for additional traits other than body size. Further work could also address the significance of uncertainty in parameter estimates for predicted food web responses to environmental change.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Tom Burr ◽  
Alexei Skurikhin

Approximate Bayesian computation (ABC) is an approach for using measurement data to calibrate stochastic computer models, which are common in biology applications. ABC is becoming the “go-to” option when the data and/or parameter dimension is large because it relies on user-chosen summary statistics rather than the full data and is therefore computationally feasible. One technical challenge with ABC is that the quality of the approximation to the posterior distribution of model parameters depends on the user-chosen summary statistics. In this paper, the user requirement to choose effective summary statistics in order to accurately estimate the posterior distribution of model parameters is investigated and illustrated by example, using a model and corresponding real data of mitochondrial DNA population dynamics. We show that for some choices of summary statistics, the posterior distribution of model parameters is closely approximated and for other choices of summary statistics, the posterior distribution is not closely approximated. A strategy to choose effective summary statistics is suggested in cases where the stochastic computer model can be run at many trial parameter settings, as in the example.


2017 ◽  
Author(s):  
Ye Zheng ◽  
Stéphane Aris-Brosou

AbstractStudies on Approximate Bayesian Computation (ABC) replacing the intractable likelihood function in evaluation of the posterior distribution have been developed for several years. However, their field of application has to date essentially been limited to inference in population genetics. Here, we propose to extend this approach to estimating the structure of transmission networks of viruses in human populations. In particular, we are interested in estimating the transmission parameters under four very general network structures: random, Watts-Strogatz, Barabasi-Albert and an extension that incorporates aging. Estimation was evaluated under three approaches, based on ABC, ABC-Markov chain Monte Carlo (ABC-MCMC) and ABC-Sequential Monte Carlo (ABC-SMC) samplers. We show that ABC-SMC samplers outperform both ABC and ABC-MCMC, achieving high accuracy and low variance in simulations. This approach paves the way to estimating parameters of real transmission networks of transmissible diseases.


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