PeTTSy: a computational tool for perturbation analysis of complex systems biology models

Abstract Background Over the last decade sensitivity analysis techniques have been shown to be very useful to analyse complex and high dimensional Systems Biology models. However, many of the currently available toolboxes have either used parameter sampling, been focused on a restricted set of model observables of interest, studied optimisation of a objective function, or have not dealt with multiple simultaneous model parameter changes where the changes can be permanent or temporary. Results Here we introduce our new, freely downloadable toolbox, PeTTSy (Perturbation Theory Toolbox for Systems). PeTTSy is a package for MATLAB which implements a wide array of techniques for the perturbation theory and sensitivity analysis of large and complex ordinary differential equation (ODE) based models. PeTTSy is a comprehensive modelling framework that introduces a number of new approaches and that fully addresses analysis of oscillatory systems. It examines sensitivity analysis of the models to perturbations of parameters, where the perturbation timing, strength, length and overall shape can be controlled by the user. This can be done in a system-global setting, namely, the user can determine how many parameters to perturb, by how much and for how long. PeTTSy also offers the user the ability to explore the effect of the parameter perturbations on many different types of outputs: period, phase (timing of peak) and model solutions. PeTTSy can be employed on a wide range of mathematical models including free-running and forced oscillators and signalling systems. To enable experimental optimisation using the Fisher Information Matrix it efficiently allows one to combine multiple variants of a model (i.e. a model with multiple experimental conditions) in order to determine the value of new experiments. It is especially useful in the analysis of large and complex models involving many variables and parameters. Conclusions PeTTSy is a comprehensive tool for analysing large and complex models of regulatory and signalling systems. It allows for simulation and analysis of models under a variety of environmental conditions and for experimental optimisation of complex combined experiments. With its unique set of tools it makes a valuable addition to the current library of sensitivity analysis toolboxes. We believe that this software will be of great use to the wider biological, systems biology and modelling communities

PeTTSy : a computational tool for perturbation analysis of complex systems biology models

Background Over the last decade sensitivity analysis techniques have been shown to be very useful to analyse complex and high dimensional Systems Biology models. However, many of the currently available toolboxes have either used parameter sampling, been focused on a restricted set of model observables of interest, studied optimisation of a objective function, or have not dealt with multiple simultaneous model parameter changes where the changes can be permanent or temporary. Results Here we introduce our new, freely downloadable toolbox, PeTTSy (Perturbation Theory Toolbox for Systems). PeTTSy is a package for MATLAB which implements a wide array of techniques for the perturbation theory and sensitivity analysis of large and complex ordinary differential equation (ODE) based models. PeTTSy is a comprehensive modelling framework that introduces a number of new approaches and that fully addresses analysis of oscillatory systems. It examines sensitivity analysis of the models to perturbations of parameters, where the perturbation timing, strength, length and overall shape can be controlled by the user. This can be done in a system-global setting, namely, the user can determine how many parameters to perturb, by how much and for how long. PeTTSy also offers the user the ability to explore the effect of the parameter perturbations on many different types of outputs: period, phase (timing of peak) and model solutions. PeTTSy can be employed on a wide range of mathematical models including free-running and forced oscillators and signalling systems. To enable experimental optimisation using the Fisher Information Matrix it efficiently allows one to combine multiple variants of a model (i.e. a model with multiple experimental conditions) in order to determine the value of new experiments. It is especially useful in the analysis of large and complex models involving many variables and parameters. Conclusions PeTTSy is a comprehensive tool for analysing large and complex models of regulatory and signalling systems. It allows for simulation and analysis of models under a variety of environmental conditions and for experimental optimisation of complex combined experiments. With its unique set of tools it makes a valuable addition to the current library of sensitivity analysis toolboxes. We believe that this software will be of great use to the wider biological, systems biology and modelling communities

Coherence Resonance and Noise-Induced Synchronization in Globally Coupled Hodgkin-Huxley Neurons

The coherence resonance (CR) of globally coupled Hodgkin-Huxley neurons is studied. When the neurons are set in the subthreshold regime near the firing threshold, the additive noise induces limit cycles. The coherence of the system is optimized by the noise. A bell-shaped curve is found for the peak height of power spectra of the spike train, being significantly different from a monotonic behavior for the single neuron. The coupling of the network can enhance CR in two different ways. In particular, when the coupling is strong enough, the synchronization of the system is induced and optimized by the noise. This synchronization leads to a high and wide plateau in the local measure of coherence curve. The local-noise-induced limit cycle can evolve to a refined spatiotemporal order through the dynamical optimization among the autonomous oscillation of an individual neuron, the coupling of the network, and the local noise.Comment: five pages, five figure

Stochastic synchronization in globally coupled phase oscillators

Cooperative effects of periodic force and noise in globally Cooperative effects of periodic force and noise in globally coupled systems are studied using a nonlinear diffusion equation for the number density. The amplitude of the order parameter oscillation is enhanced in an intermediate range of noise strength for a globally coupled bistable system, and the order parameter oscillation is entrained to the external periodic force in an intermediate range of noise strength. These enhancement phenomena of the response of the order parameter in the deterministic equations are interpreted as stochastic resonance and stochastic synchronization in globally coupled systems.Comment: 5 figure

Experimental Study of Noise-induced Phase Synchronization in Vertical-cavity Lasers

We report the experimental evidence of noise-induced phase synchronization in a vertical cavity laser. The polarized laser emission is entrained with the input periodic pump modulation when an optimal amount of white, gaussian noise is applied. We characterize the phenomenon, evaluating the average frequency of the output signal and the diffusion coefficient of the phase difference variable. Their values are roughly independent on different waveforms of periodic input, provided that a simple condition for the amplitudes is satisfied. The experimental results are compared with numerical simulations of a Langevin model

Phase synchronization and noise-induced resonance in systems of coupled oscillators

We study synchronization and noise-induced resonance phenomena in systems of globally coupled oscillators, each possessing finite inertia. The behavior of the order parameter, which measures collective synchronization of the system, is investigated as the noise level and the coupling strength are varied, and hysteretic behavior is manifested. The power spectrum of the phase velocity is also examined and the quality factor as well as the response function is obtained to reveal noise-induced resonance behavior.Comment: to be published in Phys. Rev.

Synchronization and resonance in a driven system of coupled oscillators

We study the noise effects in a driven system of globally coupled oscillators, with particular attention to the interplay between driving and noise. The self-consistency equation for the order parameter, which measures the collective synchronization of the system, is derived; it is found that the total order parameter decreases monotonically with noise, indicating overall suppression of synchronization. Still, for large coupling strengths, there exists an optimal noise level at which the periodic (ac) component of the order parameter reaches its maximum. The response of the phase velocity is also examined and found to display resonance behavior.Comment: 17 pages, 3 figure

Multifractal characterization of stochastic resonance

We use a multifractal formalism to study the effect of stochastic resonance in a noisy bistable system driven by various input signals. To characterize the response of a stochastic bistable system we introduce a new measure based on the calculation of a singularity spectrum for a return time sequence. We use wavelet transform modulus maxima method for the singularity spectrum computations. It is shown that the degree of multifractality defined as a width of singularity spectrum can be successfully used as a measure of complexity both in the case of periodic and aperiodic (stochastic or chaotic) input signals. We show that in the case of periodic driving force singularity spectrum can change its structure qualitatively becoming monofractal in the regime of stochastic synchronization. This fact allows us to consider the degree of multifractality as a new measure of stochastic synchronization also. Moreover, our calculations have shown that the effect of stochastic resonance can be catched by this measure even from a very short return time sequence. We use also the proposed approach to characterize the noise-enhanced dynamics of a coupled stochastic neurons model.Comment: 10 pages, 21 EPS-figures, RevTe

Lower plate structure and upper plate deformational segmentation at the Sunda-Banda arc transition, Indonesia

The Sunda‐Banda arc transition at the eastern termination of the Sunda margin (Indonesia) represents a unique natural laboratory to study the effects of lower plate variability on upper plate deformational segmentation. Neighboring margin segments display a high degree of structural diversity of the incoming plate (transition from an oceanic to a continental lower plate, presence/absence of an oceanic plateau, variability of subducting seafloor morphology) as well as a wide range of corresponding fore‐arc structures, including a large sedimentary basin and an accretionary prism/outer arc high of variable size and shape. Here, we present results of a combined analysis of seismic wide‐angle refraction, multichannel streamer and gravity data recorded in two trench normal corridors located offshore the islands of Lombok (116°E) and Sumba (119°E). On the incoming plate, the results reveal a 8.6–9.0 km thick oceanic crust, which is progressively faulted and altered when approaching the trench, where upper mantle velocities are reduced to ∼7.5 km/s. The outer arc high, located between the trench and the fore‐arc basin, is characterized by sedimentary‐type velocities (Vp < 5.5 km/s) down to the top of the subducting slab (∼13 km depth). The oceanic slab can be traced over 70–100 km distance beneath the fore arc. A shallow serpentinized mantle wedge at ∼16 km depth offshore Lombok is absent offshore Sumba, where our models reveal the transition to the collisional regime farther to the east and to the Sumba block in the north. Our results allow a detailed view into the complex structure of both the deeper and shallower portions of the eastern Sunda margin

Comunidade de pesquisa global: ¿o que os padrões internacionais de coautoria dizem sobre sua estrutura?

Global research community represents a noteworthy object for sociological studies. In this paper we regards it as an entity with network structure and try to analyze the current state of this structure and its recent dynamics. Among the many various approaches to studying the network links that bring together the researchers all over the world, we choose to look at the structure of international co-authorship of research papers published in journals indexed by Scopus Elsevier database. We try to provide a general outline of the network structure, to reveal distinct regional clusters existing at the various levels of this structure, and to discover whatever significant changes took place in the network structure over the last 25 years.La comunidad de investigación global representa un objeto notable para los estudios sociológicos. En este documento, lo consideramos como una entidad con estructura de red e intentamos analizar el estado actual de esta estructura y su dinámica reciente. Entre los diversos enfoques para estudiar los enlaces de red que reúnen a los investigadores de todo el mundo, elegimos observar la estructura de la coautoría internacional de los trabajos de investigación publicados en revistas indexadas por la base de datos Scopus Elsevier. Intentamos proporcionar una descripción general de la estructura de la red, revelar los distintos grupos regionales que existen en los distintos niveles de esta estructura y descubrir los cambios significativos que tuvieron lugar en la estructura de la red durante los últimos 25 años.A comunidade global de pesquisa representa um objeto notável para os estudos sociológicos. Neste trabalho nós o consideramos como uma entidade com estrutura de rede e tentamos analisar o estado atual dessa estrutura e sua dinâmica recente. Entre as várias abordagens para o estudo dos links de rede que reúnem pesquisadores de todo o mundo, optamos por analisar a estrutura de coautoria internacional de trabalhos de pesquisa publicados em periódicos indexados pela base de dados Scopus Elsevier. Tentamos fornecer um esboço geral da estrutura da rede, revelar clusters regionais distintos existentes nos vários níveis dessa estrutura e descobrir as mudanças significativas ocorridas na estrutura da rede nos últimos 25 anos