24 resultados para Bayesian hierarchical modelling


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Details about the parameters of kinetic systems are crucial for progress in both medical and industrial research, including drug development, clinical diagnosis and biotechnology applications. Such details must be collected by a series of kinetic experiments and investigations. The correct design of the experiment is essential to collecting data suitable for analysis, modelling and deriving the correct information. We have developed a systematic and iterative Bayesian method and sets of rules for the design of enzyme kinetic experiments. Our method selects the optimum design to collect data suitable for accurate modelling and analysis and minimises the error in the parameters estimated. The rules select features of the design such as the substrate range and the number of measurements. We show here that this method can be directly applied to the study of other important kinetic systems, including drug transport, receptor binding, microbial culture and cell transport kinetics. It is possible to reduce the errors in the estimated parameters and, most importantly, increase the efficiency and cost-effectiveness by reducing the necessary amount of experiments and data points measured. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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Purpose: Acquiring details of kinetic parameters of enzymes is crucial to biochemical understanding, drug development, and clinical diagnosis in ocular diseases. The correct design of an experiment is critical to collecting data suitable for analysis, modelling and deriving the correct information. As classical design methods are not targeted to the more complex kinetics being frequently studied, attention is needed to estimate parameters of such models with low variance. Methods: We have developed Bayesian utility functions to minimise kinetic parameter variance involving differentiation of model expressions and matrix inversion. These have been applied to the simple kinetics of the enzymes in the glyoxalase pathway (of importance in posttranslational modification of proteins in cataract), and the complex kinetics of lens aldehyde dehydrogenase (also of relevance to cataract). Results: Our successful application of Bayesian statistics has allowed us to identify a set of rules for designing optimum kinetic experiments iteratively. Most importantly, the distribution of points in the range is critical; it is not simply a matter of even or multiple increases. At least 60 % must be below the KM (or plural if more than one dissociation constant) and 40% above. This choice halves the variance found using a simple even spread across the range.With both the glyoxalase system and lens aldehyde dehydrogenase we have significantly improved the variance of kinetic parameter estimation while reducing the number and costs of experiments. Conclusions: We have developed an optimal and iterative method for selecting features of design such as substrate range, number of measurements and choice of intermediate points. Our novel approach minimises parameter error and costs, and maximises experimental efficiency. It is applicable to many areas of ocular drug design, including receptor-ligand binding and immunoglobulin binding, and should be an important tool in ocular drug discovery.

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In areas such as drug development, clinical diagnosis and biotechnology research, acquiring details about the kinetic parameters of enzymes is crucial. The correct design of an experiment is critical to collecting data suitable for analysis, modelling and deriving the correct information. As classical design methods are not targeted to the more complex kinetics being frequently studied, attention is needed to estimate parameters of such models with low variance. We demonstrate that a Bayesian approach (the use of prior knowledge) can produce major gains quantifiable in terms of information, productivity and accuracy of each experiment. Developing the use of Bayesian Utility functions, we have used a systematic method to identify the optimum experimental designs for a number of kinetic model data sets. This has enabled the identification of trends between kinetic model types, sets of design rules and the key conclusion that such designs should be based on some prior knowledge of K-M and/or the kinetic model. We suggest an optimal and iterative method for selecting features of the design such as the substrate range, number of measurements and choice of intermediate points. The final design collects data suitable for accurate modelling and analysis and minimises the error in the parameters estimated. (C) 2003 Elsevier Science B.V. All rights reserved.

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Climate change is one of the major challenges facing economic systems at the start of the 21st century. Reducing greenhouse gas emissions will require both restructuring the energy supply system (production) and addressing the efficiency and sufficiency of the social uses of energy (consumption). The energy production system is a complicated supply network of interlinked sectors with 'knock-on' effects throughout the economy. End use energy consumption is governed by complex sets of interdependent cultural, social, psychological and economic variables driven by shifts in consumer preference and technological development trajectories. To date, few models have been developed for exploring alternative joint energy production-consumption systems. The aim of this work is to propose one such model. This is achieved in a methodologically coherent manner through integration of qualitative input-output models of production, with Bayesian belief network models of consumption, at point of final demand. The resulting integrated framework can be applied either (relatively) quickly and qualitatively to explore alternative energy scenarios, or as a fully developed quantitative model to derive or assess specific energy policy options. The qualitative applications are explored here.

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This paper proposes and demonstrates an approach, Skilloscopy, to the assessment of decision makers. In an increasingly sophisticated, connected and information-rich world, decision making is becoming both more important and more difficult. At the same time, modelling decision-making on computers is becoming more feasible and of interest, partly because the information-input to those decisions is increasingly on record. The aims of Skilloscopy are to rate and rank decision makers in a domain relative to each other: the aims do not include an analysis of why a decision is wrong or suboptimal, nor the modelling of the underlying cognitive process of making the decisions. In the proposed method a decision-maker is characterised by a probability distribution of their competence in choosing among quantifiable alternatives. This probability distribution is derived by classic Bayesian inference from a combination of prior belief and the evidence of the decisions. Thus, decision-makers’ skills may be better compared, rated and ranked. The proposed method is applied and evaluated in the gamedomain of Chess. A large set of games by players across a broad range of the World Chess Federation (FIDE) Elo ratings has been used to infer the distribution of players’ rating directly from the moves they play rather than from game outcomes. Demonstration applications address questions frequently asked by the Chess community regarding the stability of the Elo rating scale, the comparison of players of different eras and/or leagues, and controversial incidents possibly involving fraud. The method of Skilloscopy may be applied in any decision domain where the value of the decision-options can be quantified.

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We present, pedagogically, the Bayesian approach to composed error models under alternative, hierarchical characterizations; demonstrate, briefly, the Bayesian approach to model comparison using recent advances in Markov Chain Monte Carlo (MCMC) methods; and illustrate, empirically, the value of these techniques to natural resource economics and coastal fisheries management, in particular. The Bayesian approach to fisheries efficiency analysis is interesting for at least three reasons. First, it is a robust and highly flexible alternative to commonly applied, frequentist procedures, which dominate the literature. Second,the Bayesian approach is extremely simple to implement, requiring only a modest addition to most natural-resource economist tool-kits. Third, despite its attractions, applications of Bayesian methodology in coastal fisheries management are few.

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We consider the forecasting of macroeconomic variables that are subject to revisions, using Bayesian vintage-based vector autoregressions. The prior incorporates the belief that, after the first few data releases, subsequent ones are likely to consist of revisions that are largely unpredictable. The Bayesian approach allows the joint modelling of the data revisions of more than one variable, while keeping the concomitant increase in parameter estimation uncertainty manageable. Our model provides markedly more accurate forecasts of post-revision values of inflation than do other models in the literature.

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This paper investigates the feasibility of using approximate Bayesian computation (ABC) to calibrate and evaluate complex individual-based models (IBMs). As ABC evolves, various versions are emerging, but here we only explore the most accessible version, rejection-ABC. Rejection-ABC involves running models a large number of times, with parameters drawn randomly from their prior distributions, and then retaining the simulations closest to the observations. Although well-established in some fields, whether ABC will work with ecological IBMs is still uncertain. Rejection-ABC was applied to an existing 14-parameter earthworm energy budget IBM for which the available data consist of body mass growth and cocoon production in four experiments. ABC was able to narrow the posterior distributions of seven parameters, estimating credible intervals for each. ABC’s accepted values produced slightly better fits than literature values do. The accuracy of the analysis was assessed using cross-validation and coverage, currently the best available tests. Of the seven unnarrowed parameters, ABC revealed that three were correlated with other parameters, while the remaining four were found to be not estimable given the data available. It is often desirable to compare models to see whether all component modules are necessary. Here we used ABC model selection to compare the full model with a simplified version which removed the earthworm’s movement and much of the energy budget. We are able to show that inclusion of the energy budget is necessary for a good fit to the data. We show how our methodology can inform future modelling cycles, and briefly discuss how more advanced versions of ABC may be applicable to IBMs. We conclude that ABC has the potential to represent uncertainty in model structure, parameters and predictions, and to embed the often complex process of optimizing an IBM’s structure and parameters within an established statistical framework, thereby making the process more transparent and objective.

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Land cover data derived from satellites are commonly used to prescribe inputs to models of the land surface. Since such data inevitably contains errors, quantifying how uncertainties in the data affect a model’s output is important. To do so, a spatial distribution of possible land cover values is required to propagate through the model’s simulation. However, at large scales, such as those required for climate models, such spatial modelling can be difficult. Also, computer models often require land cover proportions at sites larger than the original map scale as inputs, and it is the uncertainty in these proportions that this article discusses. This paper describes a Monte Carlo sampling scheme that generates realisations of land cover proportions from the posterior distribution as implied by a Bayesian analysis that combines spatial information in the land cover map and its associated confusion matrix. The technique is computationally simple and has been applied previously to the Land Cover Map 2000 for the region of England and Wales. This article demonstrates the ability of the technique to scale up to large (global) satellite derived land cover maps and reports its application to the GlobCover 2009 data product. The results show that, in general, the GlobCover data possesses only small biases, with the largest belonging to non–vegetated surfaces. In vegetated surfaces, the most prominent area of uncertainty is Southern Africa, which represents a complex heterogeneous landscape. It is also clear from this study that greater resources need to be devoted to the construction of comprehensive confusion matrices.