Visualization of complex biological systems: An immune response model using OpenGL

In this paper we present an update on our novel visualization technologies based on cellular immune interaction from both large-scale spatial and temporal perspectives. We do so with a primary motive: to present a visually and behaviourally realistic environment to the community of experimental biologists and physicians such that their knowledge and expertise may be more readily integrated into the model creation and calibration process. Visualization aids understanding as we rely on visual perception to make crucial decisions. For example, with our initial model, we can visualize the dynamics of an idealized lymphatic compartment, with antigen presenting cells (APC) and cytotoxic T lymphocyte (CTL) cells. The visualization technology presented here offers the researcher the ability to start, pause, zoom-in, zoom-out and navigate in 3-dimensions through an idealised lymphatic compartment.

Evaluating functional network inference using simulations of complex biological systems.

MOTIVATION: Although many network inference algorithms have been presented in the bioinformatics literature, no suitable approach has been formulated for evaluating their effectiveness at recovering models of complex biological systems from limited data. To overcome this limitation, we propose an approach to evaluate network inference algorithms according to their ability to recover a complex functional network from biologically reasonable simulated data. RESULTS: We designed a simulator to generate data representing a complex biological system at multiple levels of organization: behaviour, neural anatomy, brain electrophysiology, and gene expression of songbirds. About 90% of the simulated variables are unregulated by other variables in the system and are included simply as distracters. We sampled the simulated data at intervals as one would sample from a biological system in practice, and then used the sampled data to evaluate the effectiveness of an algorithm we developed for functional network inference. We found that our algorithm is highly effective at recovering the functional network structure of the simulated system-including the irrelevance of unregulated variables-from sampled data alone. To assess the reproducibility of these results, we tested our inference algorithm on 50 separately simulated sets of data and it consistently recovered almost perfectly the complex functional network structure underlying the simulated data. To our knowledge, this is the first approach for evaluating the effectiveness of functional network inference algorithms at recovering models from limited data. Our simulation approach also enables researchers a priori to design experiments and data-collection protocols that are amenable to functional network inference.

Memory and Epileptogenesis in Complex Biological and Simulated Systems

Oscillations of neural activity may bind widespread cortical areas into a neural representation that encodes disparate aspects of an event. In order to test this theory we have turned to data collected from complex partial epilepsy (CPE) patients with chronically implanted depth electrodes. Data from regions critical to word and face information processing was analyzed using spectral coherence measurements. Similar analyses of intracranial EEG (iEEG) during seizure episodes display HippoCampal Formation (HCF)—NeoCortical (NC) spectral coherence patterns that are characteristic of specific seizure stages (Klopp et al. 1996). We are now building a computational memory model to examine whether spatio-temporal patterns of human iEEG spectral coherence emerge in a computer simulation of HCF cellular distribution, membrane physiology and synaptic connectivity. Once the model is reasonably scaled it will be used as a tool to explore neural parameters that are critical to memory formation and epileptogenesis.

Mapping fibre orientation in complex-shaped biological systems with micrometre resolution by scanning X-ray microdiffraction

A fully automated procedure to extract and to image local fibre orientation in biological tissues from scanning X-ray diffraction is presented. The preferred chitin fibre orientation in the flow sensing system of crickets is determined with high spatial resolution by applying synchrotron radiation based X-ray microbeam diffraction in conjunction with advanced sample sectioning using a UV micro-laser. The data analysis is based on an automated detection of azimuthal diffraction maxima after 2D convolution filtering (smoothing) of the 2D diffraction patterns. Under the assumption of crystallographic fibre symmetry around the morphological fibre axis, the evaluation method allows mapping the three-dimensional orientation of the fibre axes in space. The resulting two-dimensional maps of the local fibre orientations - together with the complex shape of the flow sensing system - may be useful for a better understanding of the mechanical optimization of such tissues.

Some novel techniques of parameter estimation for the dynamical models in biological systems

Inverse problems based on using experimental data to estimate unknown parameters of a system often arise in biological and chaotic systems. In this paper, we consider parameter estimation in systems biology involving linear and non-linear complex dynamical models, including the Michaelis–Menten enzyme kinetic system, a dynamical model of competence induction in Bacillus subtilis bacteria and a model of feedback bypass in B. subtilis bacteria. We propose some novel techniques for inverse problems. Firstly, we establish an approximation of a non-linear differential algebraic equation that corresponds to the given biological systems. Secondly, we use the Picard contraction mapping, collage methods and numerical integration techniques to convert the parameter estimation into a minimization problem of the parameters. We propose two optimization techniques: a grid approximation method and a modified hybrid Nelder–Mead simplex search and particle swarm optimization (MH-NMSS-PSO) for non-linear parameter estimation. The two techniques are used for parameter estimation in a model of competence induction in B. subtilis bacteria with noisy data. The MH-NMSS-PSO scheme is applied to a dynamical model of competence induction in B. subtilis bacteria based on experimental data and the model for feedback bypass. Numerical results demonstrate the effectiveness of our approach.

The use of metabolomics in the study of metals in biological systems

Metabolomics may be defined as the comprehensive quantitative and/or qualitative analysis of all metabolites present in a bio-fluid, cell, tissue, or organism. It is essentially the study of biochemical phenotypes (or metabotypes). Metabolic profiles are context dependent, and vary in response to a variety of factors including environment and environmental stimuli, health status, disease and a myriad of other factors; as such, metabolomics has been applied to a wide range of fields and has been increasingly utilised to the study of the roles played by metals in a range of biological systems as well as, encouragingly, in understanding the underlying biochemical mechanisms. The role of metals (and metalloids) in biological organisms is complex and the majority of studies in this area have been performed in plants but the fields of natural product chemistry, human health and even bacterial corrosion of water distribution systems have been investigated using this technique. In this review some of the novel approaches in which the metabolomics toolbox has been used to unravel the roles of metals and metalloids in a range of biological systems are discussed and suggestions made for future research.

Robust multivariable control of complex biological processes

This paper addresses advanced control of a biological nutrient removal (BNR) activated sludge process. Based on a previously validated distributed parameter model of the BNR activated sludge process, we present robust multivariable controller designs for the process, involving loop shaping of plant model, robust stability and performance analyses. Results from three design case studies showed that a multivariable controller with stability margins of 0.163, 0.492 and 1.062 measured by the normalised coprime factor, multiplicative and additive uncertainties respectively give the best results for meeting performance robustness specifications. The controller robustly stabilises effluent nutrients in the presence of uncertainties with the behaviour of phosphorus accumulating organisms as well as to effectively attenuate major disturbances introduced as step changes. This study also shows that, performance of the multivariable robust controller is superior to multi-loops SISO PI controllers for regulating the BNR activated sludge process in terms of robust stability and performance and controlling the process using inlet feed flowrate is infeasible. (C) 2003 Elsevier Ltd. All rights reserved.

Managing infrastructure transitions : a complex adaptive systems perspective

Engineering assets such as roads, rail, bridges and other forms of public works are vital to the effective functioning of societies {Herder, 2006 #128}. Proficient provision of this physical infrastructure is therefore one of the key activities of government {Lædre, 2006 #123}. In order to ensure engineering assets are procured and maintained on behalf of citizens, government needs to devise the appropriate policy and institutional architecture for this purpose. The changing institutional arrangements around the procurement of engineering assets are the focus of this paper. The paper describes and analyses the transition to new, more collaborative forms of procurement arrangements which are becoming increasingly prevalent in Australia and other OECD countries. Such fundamental shifts from competitive to more collaborative approaches to project governance can be viewed as a major transition in procurement system arrangements. In many ways such changes mirror the shift from New Public Management, with its emphasis on the use of market mechanisms to achieve efficiencies {Hood, 1991 #166}, towards more collaborative approaches to service delivery, such as those under network governance arrangements {Keast, 2007 #925}. However, just as traditional forms of procurement in a market context resulted in unexpected outcomes for industry, such as a fragmented industry afflicted by chronic litigation {Dubois, 2002 #9}, the change to more collaborative forms of procurement is unlikely to be a panacea to the problems of procurement, and may well also have unintended consequences. This paper argues that perspectives from complex adaptive systems (CAS) theory can contribute to the theory and practice of managing system transitions. In particular the concept of emergence provides a key theoretical construct to understand the aggregate effect that individual project governance arrangements can have upon the structure of specific industries, which in turn impact individual projects. Emergence is understood here as the macro structure that emerges out of the interaction of agents in the system {Holland, 1998 #100; Tang, 2006 #51}.

The organisation of action in complex neurobiological systems

This chapter elucidates key ideas behind neurocomputational and ecological dynamics and perspectives of understanding the organisation of action in complex neurobiological systems. The need to study the close link between neurobiological systems and their environments (particularly their sensory and movement subsystems and the surrounding energy sources) is advocated. It is proposed how degeneracy in complex neurobiological systems provides the basis for functional variability in organisation of action. In such systems processes of cognition and action facilitate the specific interactions of each performer with particular task and environmental constraints.

Complex Urban Systems

Presentation about research projects that build understanding of urban design and interactions and plan for future opportunities. What do we need to model?

Networks as a novel tool for studying team ball sports as complex social systems

This paper describes and evaluates the novel utility of network methods for understanding human interpersonal interactions within social neurobiological systems such as sports teams. We show how collective system networks are supported by the sum of interpersonal interactions that emerge from the activity of system agents (such as players in a sports team). To test this idea we trialled the methodology in analyses of intra-team collective behaviours in the team sport of water polo. We observed that the number of interactions between team members resulted in varied intra-team coordination patterns of play, differentiating between successful and unsuccessful performance outcomes. Future research on small-world networks methodologies needs to formalize measures of node connections in analyses of collective behaviours in sports teams, to verify whether a high frequency of interactions is needed between players in order to achieve competitive performance outcomes.

A Krylov-based finite state projection algorithm for solving the chemical master equation arising in the discrete modelling of biological systems

Biochemical reactions underlying genetic regulation are often modelled as a continuous-time, discrete-state, Markov process, and the evolution of the associated probability density is described by the so-called chemical master equation (CME). However the CME is typically difficult to solve, since the state-space involved can be very large or even countably infinite. Recently a finite state projection method (FSP) that truncates the state-space was suggested and shown to be effective in an example of a model of the Pap-pili epigenetic switch. However in this example, both the model and the final time at which the solution was computed, were relatively small. Presented here is a Krylov FSP algorithm based on a combination of state-space truncation and inexact matrix-vector product routines. This allows larger-scale models to be studied and solutions for larger final times to be computed in a realistic execution time. Additionally the new method computes the solution at intermediate times at virtually no extra cost, since it is derived from Krylov-type methods for computing matrix exponentials. For the purpose of comparison the new algorithm is applied to the model of the Pap-pili epigenetic switch, where the original FSP was first demonstrated. Also the method is applied to a more sophisticated model of regulated transcription. Numerical results indicate that the new approach is significantly faster and extendable to larger biological models.