ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

Background: Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, with the goal to gain a better understanding of the system. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. Although there exist sophisticated algorithms to determine the dynamics of discrete models, their implementations usually require labor-intensive formatting of the model formulation, and they are oftentimes not accessible to users without programming skills. Efficient analysis methods are needed that are accessible to modelers and easy to use. Method: By converting discrete models into algebraic models, tools from computational algebra can be used to analyze their dynamics. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Results: A method for efficiently identifying attractors, and the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness, i.e., while the number of nodes in a biological network may be quite large, each node is affected only by a small number of other nodes, and robustness, i.e., small number of attractors

Probabilistic Guarded P Systems, A New Formal Modelling Framework

Multienvironment P systems constitute a general, formal framework for modelling the dynamics of population biology, which consists of two main approaches: stochastic and probabilistic. The framework has been successfully used to model biologic systems at both micro (e.g. bacteria colony) and macro (e.g. real ecosystems) levels, respectively. In this paper, we extend the general framework in order to include a new case study related to P. Oleracea species. The extension is made by a new variant within the probabilistic approach, called Probabilistic Guarded P systems (in short, PGP systems). We provide a formal definition, a simulation algorithm to capture the dynamics, and a survey of the associated software.Ministerio de Economía y Competitividad TIN2012- 37434Junta de Andalucía P08-TIC-0420

Bayesian Updating, Model Class Selection and Robust Stochastic Predictions of Structural Response

A fundamental issue when predicting structural response by using mathematical models is how to treat both modeling and excitation uncertainty. A general framework for this is presented which uses probability as a multi-valued conditional logic for quantitative plausible reasoning in the presence of uncertainty due to incomplete information. The fundamental probability models that represent the structure’s uncertain behavior are specified by the choice of a stochastic system model class: a set of input-output probability models for the structure and a prior probability distribution over this set that quantifies the relative plausibility of each model. A model class can be constructed from a parameterized deterministic structural model by stochastic embedding utilizing Jaynes’ Principle of Maximum Information Entropy. Robust predictive analyses use the entire model class with the probabilistic predictions of each model being weighted by its prior probability, or if structural response data is available, by its posterior probability from Bayes’ Theorem for the model class. Additional robustness to modeling uncertainty comes from combining the robust predictions of each model class in a set of competing candidates weighted by the prior or posterior probability of the model class, the latter being computed from Bayes’ Theorem. This higherlevel application of Bayes’ Theorem automatically applies a quantitative Ockham razor that penalizes the data-fit of more complex model classes that extract more information from the data. Robust predictive analyses involve integrals over highdimensional spaces that usually must be evaluated numerically. Published applications have used Laplace's method of asymptotic approximation or Markov Chain Monte Carlo algorithms

Scalable Approach to Uncertainty Quantification and Robust Design of Interconnected Dynamical Systems

Development of robust dynamical systems and networks such as autonomous aircraft systems capable of accomplishing complex missions faces challenges due to the dynamically evolving uncertainties coming from model uncertainties, necessity to operate in a hostile cluttered urban environment, and the distributed and dynamic nature of the communication and computation resources. Model-based robust design is difficult because of the complexity of the hybrid dynamic models including continuous vehicle dynamics, the discrete models of computations and communications, and the size of the problem. We will overview recent advances in methodology and tools to model, analyze, and design robust autonomous aerospace systems operating in uncertain environment, with stress on efficient uncertainty quantification and robust design using the case studies of the mission including model-based target tracking and search, and trajectory planning in uncertain urban environment. To show that the methodology is generally applicable to uncertain dynamical systems, we will also show examples of application of the new methods to efficient uncertainty quantification of energy usage in buildings, and stability assessment of interconnected power networks

Bridging the Gap between Probabilistic and Deterministic Models: A Simulation Study on a Variational Bayes Predictive Coding Recurrent Neural Network Model

The current paper proposes a novel variational Bayes predictive coding RNN model, which can learn to generate fluctuated temporal patterns from exemplars. The model learns to maximize the lower bound of the weighted sum of the regularization and reconstruction error terms. We examined how this weighting can affect development of different types of information processing while learning fluctuated temporal patterns. Simulation results show that strong weighting of the reconstruction term causes the development of deterministic chaos for imitating the randomness observed in target sequences, while strong weighting of the regularization term causes the development of stochastic dynamics imitating probabilistic processes observed in targets. Moreover, results indicate that the most generalized learning emerges between these two extremes. The paper concludes with implications in terms of the underlying neuronal mechanisms for autism spectrum disorder and for free action.Comment: This paper is accepted the 24th International Conference On Neural Information Processing (ICONIP 2017). The previous submission to arXiv is replaced by this version because there was an error in Equation

Probabilistic model checking of complex biological pathways

Probabilistic model checking is a formal verification technique that has been successfully applied to the analysis of systems from a broad range of domains, including security and communication protocols, distributed algorithms and power management. In this paper we illustrate its applicability to a complex biological system: the FGF (Fibroblast Growth Factor) signalling pathway. We give a detailed description of how this case study can be modelled in the probabilistic model checker PRISM, discussing some of the issues that arise in doing so, and show how we can thus examine a rich selection of quantitative properties of this model. We present experimental results for the case study under several different scenarios and provide a detailed analysis, illustrating how this approach can be used to yield a better understanding of the dynamics of the pathway

A probabilistic approach to model-based adaptive control for damping of interarea oscillations

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