Thermodynamic large fluctuations from uniformized dynamics

Large fluctuations have received considerable attention as they encode information on the fine-scale dynamics. Large deviation relations known as fluctuation theorems also capture crucial nonequilibrium thermodynamical properties. Here we report that, using the technique of uniformization, the thermodynamic large deviation functions of continuous-time Markov processes can be obtained from Markov chains evolving in discrete time. This formulation offers new theoretical and numerical approaches to explore large deviation properties. In particular, the time evolution of autonomous and non-autonomous processes can be expressed in terms of a single Poisson rate. In this way the uniformization procedure leads to a simple and efficient way to simulate stochastic trajectories that reproduce the exact fluxes statistics. We illustrate the formalism for the current fluctuations in a stochastic pump model

A Modified Uniformization Method for the Solution of the Chemical Master Equation

The chemical master equation is considered an accurate description of general chemical systems, and especially so for modeling cell cycle and gene regulatory networks. This paper proposes an efficient way of solving the chemical master equation for some prototypical problems in systems biology. A comparison between this new approach and some traditional approaches is also given

Efficient Transition Probability Computation for Continuous-Time Branching Processes via Compressed Sensing

Branching processes are a class of continuous-time Markov chains (CTMCs) with ubiquitous applications. A general difficulty in statistical inference under partially observed CTMC models arises in computing transition probabilities when the discrete state space is large or uncountable. Classical methods such as matrix exponentiation are infeasible for large or countably infinite state spaces, and sampling-based alternatives are computationally intensive, requiring a large integration step to impute over all possible hidden events. Recent work has successfully applied generating function techniques to computing transition probabilities for linear multitype branching processes. While these techniques often require significantly fewer computations than matrix exponentiation, they also become prohibitive in applications with large populations. We propose a compressed sensing framework that significantly accelerates the generating function method, decreasing computational cost up to a logarithmic factor by only assuming the probability mass of transitions is sparse. We demonstrate accurate and efficient transition probability computations in branching process models for hematopoiesis and transposable element evolution.Comment: 18 pages, 4 figures, 2 table

Model Checking CSL for Markov Population Models

Markov population models (MPMs) are a widely used modelling formalism in the area of computational biology and related areas. The semantics of a MPM is an infinite-state continuous-time Markov chain. In this paper, we use the established continuous stochastic logic (CSL) to express properties of Markov population models. This allows us to express important measures of biological systems, such as probabilistic reachability, survivability, oscillations, switching times between attractor regions, and various others. Because of the infinite state space, available analysis techniques only apply to a very restricted subset of CSL properties. We present a full algorithm for model checking CSL for MPMs, and provide experimental evidence showing that our method is effective.Comment: In Proceedings QAPL 2014, arXiv:1406.156

Efficient Bayesian inference under the structured coalescent

Motivation: Population structure significantly affects evolutionary dynamics. Such structure may be due to spatial segregation, but may also reflect any other gene-flow-limiting aspect of a model. In combination with the structured coalescent, this fact can be used to inform phylogenetic tree reconstruction, as well as to infer parameters such as migration rates and subpopulation sizes from annotated sequence data. However, conducting Bayesian inference under the structured coalescent is impeded by the difficulty of constructing Markov Chain Monte Carlo (MCMC) sampling algorithms (samplers) capable of efficiently exploring the state space. Results: In this article, we present a new MCMC sampler capable of sampling from posterior distributions over structured trees: timed phylogenetic trees in which lineages are associated with the distinct subpopulation in which they lie. The sampler includes a set of MCMC proposal functions that offer significant mixing improvements over a previously published method. Furthermore, its implementation as a BEAST 2 package ensures maximum flexibility with respect to model and prior specification. We demonstrate the usefulness of this new sampler by using it to infer migration rates and effective population sizes of H3N2 influenza between New Zealand, New York and Hong Kong from publicly available hemagglutinin (HA) gene sequences under the structured coalescent. Availability and implementation: The sampler has been implemented as a publicly available BEAST 2 package that is distributed under version 3 of the GNU General Public License at http://compevol.github.io/MultiTypeTree. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

State aggregation for fast likelihood computations in molecular evolution.

MOTIVATION: Codon models are widely used to identify the signature of selection at the molecular level and to test for changes in selective pressure during the evolution of genes encoding proteins. The large size of the state space of the Markov processes used to model codon evolution makes it difficult to use these models with large biological datasets. We propose here to use state aggregation to reduce the state space of codon models and, thus, improve the computational performance of likelihood estimation on these models. RESULTS: We show that this heuristic speeds up the computations of the M0 and branch-site models up to 6.8 times. We also show through simulations that state aggregation does not introduce a detectable bias. We analysed a real dataset and show that aggregation provides highly correlated predictions compared to the full likelihood computations. Finally, state aggregation is a very general approach and can be applied to any continuous-time Markov process-based model with large state space, such as amino acid and coevolution models. We therefore discuss different ways to apply state aggregation to Markov models used in phylogenetics. AVAILABILITY: The heuristic is implemented in the godon package (https://bitbucket.org/Davydov/godon) and in a version of FastCodeML (https://gitlab.isb-sib.ch/phylo/fastcodeml). CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

The application of Approximate Dynamic Programming techniques

Koole, G.M. [Promotor]Bhulai, S. [Copromotor