Efficient and accurate experimental design for enzyme kinetics: Bayesian studies reveal a systematic approach

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.

A study of the effect of heat source location in a ventilated room using multiple regression analysis

Multiple regression analysis is a statistical technique which allows to predict a dependent variable from m ore than one independent variable and also to determine influential independent variables. Using experimental data, in this study the multiple regression analysis is applied to predict the room mean velocity and determine the most influencing parameters on the velocity. More than 120 experiments for four different heat source locations were carried out in a test chamber with a high level wall mounted air supply terminal at air change rates 3-6 ach. The influence of the environmental parameters such as supply air momentum, room heat load, Archimedes number and local temperature ratio, were examined by two methods: a simple regression analysis incorporated into scatter matrix plots and multiple stepwise regression analysis. It is concluded that, when a heat source is located along the jet centre line, the supply momentum mainly influences the room mean velocity regardless of the plume strength. However, when the heat source is located outside the jet region, the local temperature ratio (the inverse of the local heat removal effectiveness) is a major influencing parameter.

Regression, developmental trajectory and associated problems in disorders in the autism spectrum: the SNAP study

We report rates of regression and associated findings in a population derived group of 255 children aged 9-14 years, participating in a prevalence study of autism spectrum disorders (ASD); 53 with narrowly defined autism, 105 with broader ASD and 97 with non-ASD neurodevelopmental problems, drawn from those with special educational needs within a population of 56,946 children. Language regression was reported in 30% with narrowly defined autism, 8% with broader ASD and less than 3% with developmental problems without ASD. A smaller group of children were identified who underwent a less clear setback. Regression was associated with higher rates of autistic symptoms and a deviation in developmental trajectory. Regression was not associated with epilepsy or gastrointestinal problems.

A combined Bayesian Markovian approach for behaviour recognition

Numerous techniques exist which can be used for the task of behavioural analysis and recognition. Common amongst these are Bayesian networks and Hidden Markov Models. Although these techniques are extremely powerful and well developed, both have important limitations. By fusing these techniques together to form Bayes-Markov chains, the advantages of both techniques can be preserved, while reducing their limitations. The Bayes-Markov technique forms the basis of a common, flexible framework for supplementing Markov chains with additional features. This results in improved user output, and aids in the rapid development of flexible and efficient behaviour recognition systems.

Fully complex-valued radial basis function networks for orthogonal least squares regression

We consider a fully complex-valued radial basis function (RBF) network for regression application. The locally regularised orthogonal least squares (LROLS) algorithm with the D-optimality experimental design, originally derived for constructing parsimonious real-valued RBF network models, is extended to the fully complex-valued RBF network. Like its real-valued counterpart, the proposed algorithm aims to achieve maximised model robustness and sparsity by combining two effective and complementary approaches. The LROLS algorithm alone is capable of producing a very parsimonious model with excellent generalisation performance while the D-optimality design criterion further enhances the model efficiency and robustness. By specifying an appropriate weighting for the D-optimality cost in the combined model selecting criterion, the entire model construction procedure becomes automatic. An example of identifying a complex-valued nonlinear channel is used to illustrate the regression application of the proposed fully complex-valued RBF network.

A sparse parallel hybrid Monte Carlo algorithm for matrix computations

In this paper we introduce a new algorithm, based on the successful work of Fathi and Alexandrov, on hybrid Monte Carlo algorithms for matrix inversion and solving systems of linear algebraic equations. This algorithm consists of two parts, approximate inversion by Monte Carlo and iterative refinement using a deterministic method. Here we present a parallel hybrid Monte Carlo algorithm, which uses Monte Carlo to generate an approximate inverse and that improves the accuracy of the inverse with an iterative refinement. The new algorithm is applied efficiently to sparse non-singular matrices. When we are solving a system of linear algebraic equations, Bx = b, the inverse matrix is used to compute the solution vector x = B(-1)b. We present results that show the efficiency of the parallel hybrid Monte Carlo algorithm in the case of sparse matrices.

Sparse multioutput radial basis function network construction using combined locally regularised orthogonal least square and D-optimality experimental design

A construction algorithm for multioutput radial basis function (RBF) network modelling is introduced by combining a locally regularised orthogonal least squares (LROLS) model selection with a D-optimality experimental design. The proposed algorithm aims to achieve maximised model robustness and sparsity via two effective and complementary approaches. The LROLS method alone is capable of producing a very parsimonious RBF network model with excellent generalisation performance. The D-optimality design criterion enhances the model efficiency and robustness. A further advantage of the combined approach is that the user only needs to specify a weighting for the D-optimality cost in the combined RBF model selecting criterion and the entire model construction procedure becomes automatic. The value of this weighting does not influence the model selection procedure critically and it can be chosen with ease from a wide range of values.

Modified radial basis function neural network using output transformation

A modified radial basis function (RBF) neural network and its identification algorithm based on observational data with heterogeneous noise are introduced. The transformed system output of Box-Cox is represented by the RBF neural network. To identify the model from observational data, the singular value decomposition of the full regression matrix consisting of basis functions formed by system input data is initially carried out and a new fast identification method is then developed using Gauss-Newton algorithm to derive the required Box-Cox transformation, based on a maximum likelihood estimator (MLE) for a model base spanned by the largest eigenvectors. Finally, the Box-Cox transformation-based RBF neural network, with good generalisation and sparsity, is identified based on the derived optimal Box-Cox transformation and an orthogonal forward regression algorithm using a pseudo-PRESS statistic to select a sparse RBF model with good generalisation. The proposed algorithm and its efficacy are demonstrated with numerical examples.