Bayesian inference of biochemical kinetic parameters using the linear noise approximation

Background Fluorescent and luminescent gene reporters allow us to dynamically quantify changes in molecular species concentration over time on the single cell level. The mathematical modeling of their interaction through multivariate dynamical models requires the deveopment of effective statistical methods to calibrate such models against available data. Given the prevalence of stochasticity and noise in biochemical systems inference for stochastic models is of special interest. In this paper we present a simple and computationally efficient algorithm for the estimation of biochemical kinetic parameters from gene reporter data. Results We use the linear noise approximation to model biochemical reactions through a stochastic dynamic model which essentially approximates a diffusion model by an ordinary differential equation model with an appropriately defined noise process. An explicit formula for the likelihood function can be derived allowing for computationally efficient parameter estimation. The proposed algorithm is embedded in a Bayesian framework and inference is performed using Markov chain Monte Carlo. Conclusion The major advantage of the method is that in contrast to the more established diffusion approximation based methods the computationally costly methods of data augmentation are not necessary. Our approach also allows for unobserved variables and measurement error. The application of the method to both simulated and experimental data shows that the proposed methodology provides a useful alternative to diffusion approximation based methods

An iterative semi-implicit scheme with robust damping

An efficient, iterative semi-implicit (SI) numerical method for the time integration of stiff wave systems is presented. Physics-based assumptions are used to derive a convergent iterative formulation of the SI scheme which enables the monitoring and control of the error introduced by the SI operator. This iteration essentially turns a semi-implicit method into a fully implicit method. Accuracy, rather than stability, determines the timestep. The scheme is second-order accurate and shown to be equivalent to a simple preconditioning method. We show how the diffusion operators can be handled so as to yield the property of robust damping, i.e., dissipating the solution at all values of the parameter \mathcal D\dt, where $\mathcal D$ is a diffusion operator and \dt the timestep. The overall scheme remains second-order accurate even if the advection and diffusion operators do not commute. In the limit of no physical dissipation, and for a linear test wave problem, the method is shown to be symplectic. The method is tested on the problem of Kinetic Alfv\'en wave mediated magnetic reconnection. A Fourier (pseudo-spectral) representation is used. A 2-field gyrofluid model is used and an efficacious k-space SI operator for this problem is demonstrated. CPU speed-up factors over a CFL-limited explicit algorithm ranging from $\sim20$ to several hundreds are obtained, while accurately capturing the results of an explicit integration. Possible extension of these results to a real-space (grid) discretization is discussed.Comment: Submitted to the Journal of Computational Physics. Clarifications and caveats in response to referees, numerical demonstration of convergence rate, generalized symplectic proo

Simple digital quantum algorithm for symmetric first order linear hyperbolic systems

This paper is devoted to the derivation of a digital quantum algorithm for the Cauchy problem for symmetric first order linear hyperbolic systems, thanks to the reservoir technique. The reservoir technique is a method designed to avoid artificial diffusion generated by first order finite volume methods approximating hyperbolic systems of conservation laws. For some class of hyperbolic systems, namely those with constant matrices in several dimensions, we show that the combination of i) the reservoir method and ii) the alternate direction iteration operator splitting approximation, allows for the derivation of algorithms only based on simple unitary transformations, thus perfectly suitable for an implementation on a quantum computer. The same approach can also be adapted to scalar one-dimensional systems with non-constant velocity by combining with a non-uniform mesh. The asymptotic computational complexity for the time evolution is determined and it is demonstrated that the quantum algorithm is more efficient than the classical version. However, in the quantum case, the solution is encoded in probability amplitudes of the quantum register. As a consequence, as with other similar quantum algorithms, a post-processing mechanism has to be used to obtain general properties of the solution because a direct reading cannot be performed as efficiently as the time evolution.Comment: 28 pages, 12 figures, major rewriting of the section describing the numerical method, simplified the presentation and notation, reorganized the sections, comments are welcome

An Investigation Into the use of Swarm Intelligence for an Evolutionary Algorithm Optimisation; The Optimisation Performance of Differential Evolution Algorithm Coupled with Stochastic Diffusion Search

The integration of Swarm Intelligence (SI) algorithms and Evolutionary algorithms (EAs) might be one of the future approaches in the Evolutionary Computation (EC). This work narrates the early research on using Stochastic Diffusion Search (SDS) -- a swarm intelligence algorithm -- to empower the Differential Evolution (DE) -- an evolutionary algorithm -- over a set of optimisation problems. The results reported herein suggest that the powerful resource allocation mechanism deployed in SDS has the potential to improve the optimisation capability of the classical evolutionary algorithm used in this experiment. Different performance measures and statistical analyses were utilised to monitor the behaviour of the final coupled algorithm

Local error estimates for adaptive simulation of the Reaction-Diffusion Master Equation via operator splitting

The efficiency of exact simulation methods for the reaction-diffusion master equation (RDME) is severely limited by the large number of diffusion events if the mesh is fine or if diffusion constants are large. Furthermore, inherent properties of exact kinetic-Monte Carlo simulation methods limit the efficiency of parallel implementations. Several approximate and hybrid methods have appeared that enable more efficient simulation of the RDME. A common feature to most of them is that they rely on splitting the system into its reaction and diffusion parts and updating them sequentially over a discrete timestep. This use of operator splitting enables more efficient simulation but it comes at the price of a temporal discretization error that depends on the size of the timestep. So far, existing methods have not attempted to estimate or control this error in a systematic manner. This makes the solvers hard to use for practitioners since they must guess an appropriate timestep. It also makes the solvers potentially less efficient than if the timesteps are adapted to control the error. Here, we derive estimates of the local error and propose a strategy to adaptively select the timestep when the RDME is simulated via a first order operator splitting. While the strategy is general and applicable to a wide range of approximate and hybrid methods, we exemplify it here by extending a previously published approximate method, the Diffusive Finite-State Projection (DFSP) method, to incorporate temporal adaptivity

Holistic Influence Maximization: Combining Scalability and Efficiency with Opinion-Aware Models

The steady growth of graph data from social networks has resulted in wide-spread research in finding solutions to the influence maximization problem. In this paper, we propose a holistic solution to the influence maximization (IM) problem. (1) We introduce an opinion-cum-interaction (OI) model that closely mirrors the real-world scenarios. Under the OI model, we introduce a novel problem of Maximizing the Effective Opinion (MEO) of influenced users. We prove that the MEO problem is NP-hard and cannot be approximated within a constant ratio unless P=NP. (2) We propose a heuristic algorithm OSIM to efficiently solve the MEO problem. To better explain the OSIM heuristic, we first introduce EaSyIM - the opinion-oblivious version of OSIM, a scalable algorithm capable of running within practical compute times on commodity hardware. In addition to serving as a fundamental building block for OSIM, EaSyIM is capable of addressing the scalability aspect - memory consumption and running time, of the IM problem as well. Empirically, our algorithms are capable of maintaining the deviation in the spread always within 5% of the best known methods in the literature. In addition, our experiments show that both OSIM and EaSyIM are effective, efficient, scalable and significantly enhance the ability to analyze real datasets.Comment: ACM SIGMOD Conference 2016, 18 pages, 29 figure

An Exact Auxiliary Variable Gibbs Sampler for a Class of Diffusions

Stochastic differential equations (SDEs) or diffusions are continuous-valued continuous-time stochastic processes widely used in the applied and mathematical sciences. Simulating paths from these processes is usually an intractable problem, and typically involves time-discretization approximations. We propose an exact Markov chain Monte Carlo sampling algorithm that involves no such time-discretization error. Our sampler is applicable to the problem of prior simulation from an SDE, posterior simulation conditioned on noisy observations, as well as parameter inference given noisy observations. Our work recasts an existing rejection sampling algorithm for a class of diffusions as a latent variable model, and then derives an auxiliary variable Gibbs sampling algorithm that targets the associated joint distribution. At a high level, the resulting algorithm involves two steps: simulating a random grid of times from an inhomogeneous Poisson process, and updating the SDE trajectory conditioned on this grid. Our work allows the vast literature of Monte Carlo sampling algorithms from the Gaussian process literature to be brought to bear to applications involving diffusions. We study our method on synthetic and real datasets, where we demonstrate superior performance over competing methods.Comment: 37 pages, 13 figure

Efficient Reactive Brownian Dynamics

We develop a Split Reactive Brownian Dynamics (SRBD) algorithm for particle simulations of reaction-diffusion systems based on the Doi or volume reactivity model, in which pairs of particles react with a specified Poisson rate if they are closer than a chosen reactive distance. In our Doi model, we ensure that the microscopic reaction rules for various association and disassociation reactions are consistent with detailed balance (time reversibility) at thermodynamic equilibrium. The SRBD algorithm uses Strang splitting in time to separate reaction and diffusion, and solves both the diffusion-only and reaction-only subproblems exactly, even at high packing densities. To efficiently process reactions without uncontrolled approximations, SRBD employs an event-driven algorithm that processes reactions in a time-ordered sequence over the duration of the time step. A grid of cells with size larger than all of the reactive distances is used to schedule and process the reactions, but unlike traditional grid-based methods such as Reaction-Diffusion Master Equation (RDME) algorithms, the results of SRBD are statistically independent of the size of the grid used to accelerate the processing of reactions. We use the SRBD algorithm to compute the effective macroscopic reaction rate for both reaction- and diffusion-limited irreversible association in three dimensions. We also study long-time tails in the time correlation functions for reversible association at thermodynamic equilibrium. Finally, we compare different particle and continuum methods on a model exhibiting a Turing-like instability and pattern formation. We find that for models in which particles diffuse off lattice, such as the Doi model, reactions lead to a spurious enhancement of the effective diffusion coefficients.Comment: To appear in J. Chem. Phy