Parameter estimation and treatment optimization in a stochastic model for immunotherapy of cancer

Adoptive Cell Transfer therapy of cancer is currently in full development and mathematical modeling is playing a critical role in this area. We study a stochastic model developed by Baar et al. in 2015 for modeling immunotherapy against melanoma skin cancer. First, we estimate the parameters of the deterministic limit of the model based on biological data of tumor growth in mice. A Nonlinear Mixed Effects Model is estimated by the Stochastic Approximation Expectation Maximization algorithm. With the estimated parameters, we head back to the stochastic model and calculate the probability that the T cells all get exhausted during the treatment. We show that for some relevant parameter values, an early relapse is due to stochastic fluctuations (complete T cells exhaustion) with a non negligible probability. Then, focusing on the relapse related to the T cell exhaustion, we propose to optimize the treatment plan (treatment doses and restimulation times) by minimizing the T cell exhaustion probability in the parameter estimation ranges.Comment: major reorganisation of the paper and the reformulation of many substantial part

Optimal vaccination in a stochastic epidemic model of two non-interacting populations

Developing robust, quantitative methods to optimize resource allocations in response to epidemics has the potential to save lives and minimize health care costs. In this paper, we develop and apply a computationally efficient algorithm that enables us to calculate the complete probability distribution for the final epidemic size in a stochastic Susceptible-Infected-Recovered (SIR) model. Based on these results, we determine the optimal allocations of a limited quantity of vaccine between two non-interacting populations. We compare the stochastic solution to results obtained for the traditional, deterministic SIR model. For intermediate quantities of vaccine, the deterministic model is a poor estimate of the optimal strategy for the more realistic, stochastic case.Comment: 21 pages, 7 figure

Approximate Bayesian computation scheme for parameter inference and model selection in dynamical systems

Approximate Bayesian computation methods can be used to evaluate posterior distributions without having to calculate likelihoods. In this paper we discuss and apply an approximate Bayesian computation (ABC) method based on sequential Monte Carlo (SMC) to estimate parameters of dynamical models. We show that ABC SMC gives information about the inferability of parameters and model sensitivity to changes in parameters, and tends to perform better than other ABC approaches. The algorithm is applied to several well known biological systems, for which parameters and their credible intervals are inferred. Moreover, we develop ABC SMC as a tool for model selection; given a range of different mathematical descriptions, ABC SMC is able to choose the best model using the standard Bayesian model selection apparatus.Comment: 26 pages, 9 figure

Ascent trajectory optimisation for a single-stage-to-orbit vehicle with hybrid propulsion

This paper addresses the design of ascent trajectories for a hybrid-engine, high performance, unmanned, single-stage-to-orbit vehicle for payload deployment into low Earth orbit. A hybrid optimisation technique that couples a population-based, stochastic algorithm with a deterministic, gradient-based technique is used to maximize the nal vehicle mass in low Earth orbit after accounting for operational constraints on the dynamic pressure, Mach number and maximum axial and normal accelerations. The control search space is first explored by the population-based algorithm, which uses a single shooting method to evaluate the performance of candidate solutions. The resultant optimal control law and corresponding trajectory are then further refined by a direct collocation method based on finite elements in time. Two distinct operational phases, one using an air-breathing propulsion mode and the second using rocket propulsion, are considered. The presence of uncertainties in the atmospheric and vehicle aerodynamic models are considered in order to quantify their effect on the performance of the vehicle. Firstly, the deterministic optimal control law is re-integrated after introducing uncertainties into the models. The proximity of the final solutions to the target states are analysed statistically. A second analysis is then performed, aimed at determining the best performance of the vehicle when these uncertainties are included directly in the optimisation. The statistical analysis of the results obtained are summarized by an expectancy curve which represents the probable vehicle performance as a function of the uncertain system parameters. This analysis can be used during the preliminary phase of design to yield valuable insights into the robustness of the performance of the vehicle to uncertainties in the specification of its parameters

A partially linearized sigma point filter for latent state estimation in nonlinear time series models

A new technique for the latent state estimation of a wide class of nonlinear time series models is proposed. In particular, we develop a partially linearized sigma point filter in which random samples of possible state values are generated at the prediction step using an exact moment matching algorithm and then a linear programming-based procedure is used in the update step of the state estimation. The effectiveness of the new ¯ltering procedure is assessed via a simulation example that deals with a highly nonlinear, multivariate time series representing an interest rate process