Since age is the most significant risk factor for the development of Alzheimer's disease (AD), it is important to understand the effect of normal ageing on brain network characteristics before we can accurately diagnose the condition based on information derived from resting state electroencephalogram (EEG) recordings, aiming to detect brain network disruption. This article proposes a novel brain functional connectivity imaging method, particularly targeting the contribution of nonlinear dynamics of functional connectivity, on distinguishing participants with AD from healthy controls (HC). We describe a parametric method established upon a Nonlinear Finite Impulse Response model, and a revised orthogonal least squares algorithm used to estimate the linear, nonlinear and combined connectivity between any two EEG channels without fitting a full model. This approach, where linear and non-linear interactions and their spatial distribution and dynamics can be estimated independently, offered us the means to dissect the dynamic brain network disruption in AD from a new perspective and to gain some insight into the dynamic behaviour of brain networks in two age groups (above and below 70) with normal cognitive function. Although linear and stationary connectivity dominates the classification contributions, quantitative results have demonstrated that nonlinear and dynamic connectivity can significantly improve the classification accuracy, barring the group of participants below the age of 70, for resting state EEG recorded during eyes open. The developed approach is generic and can be used as a powerful tool to examine brain network characteristics and disruption in a user friendly and systematic way.

An important step in the identification of cellular automata (CA) is to detect the correct neighborhood before parameter estimation. Many authors have suggested procedures based on the removal of redundant neighbors from a very large initial neighborhood one by one to find the real model, but this often induces ill conditioning and overfitting. This is true particularly for a large initial neighborhood where there are few significant terms, and this will be demonstrated by an example in this paper. By introducing a new criteria and three new techniques, this paper proposes a new adaptive fast CA orthogonal-least-square (Adaptive-FCA-OLS) algorithm, which cannot only adaptively search for the correct neighborhood without any preset tolerance but can also considerably reduce the computational complexity and memory usage. Several numerical examples demonstrate that the Adaptive-FCA-OLS algorithm has better robustness to noise and to the size of the initial neighborhood than other recently developed neighborhood detection methods in the identification of binary CA.

MOTIVATION: Human pluripotent stem cell lines persist in culture as a heterogeneous population of SSEA3 positive and SSEA3 negative cells. Tracking individual stem cells in real time can elucidate the kinetics of cells switching between the SSEA3 positive and negative substates. However, identifying a cell's substate at all time points within a cell lineage tree is technically difficult. RESULTS: A variational Bayesian Expectation Maximization (EM) with smoothed probabilities (VBEMS) algorithm for hidden Markov trees (HMT) is proposed for incomplete tree structured data. The full posterior of the HMT parameters is determined and the underflow problems associated with previous algorithms are eliminated. Example results for the prediction of the types of cells in synthetic and real stem cell lineage trees are presented. AVAILABILITY: The Matlab code for the VBEMS algorithm is freely available at http://www.acse.dept.shef.ac.uk/repository/vbems_lineage_tree/VBEMS.ZIP CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In this brief, by combining an efficient wavelet representation with a coupled map lattice model, a new family of adaptive wavelet neural networks, called lattice dynamical wavelet neural networks (LDWNNs), is introduced for spatio-temporal system identification. A new orthogonal projection pursuit (OPP) method, coupled with a particle swarm optimization (PSO) algorithm, is proposed for augmenting the proposed network. A novel two-stage hybrid training scheme is developed for constructing a parsimonious network model. In the first stage, by applying the OPP algorithm, significant wavelet neurons are adaptively and successively recruited into the network, where adjustable parameters of the associated wavelet neurons are optimized using a particle swarm optimizer. The resultant network model, obtained in the first stage, however, may be redundant. In the second stage, an orthogonal least squares algorithm is then applied to refine and improve the initially trained network by removing redundant wavelet neurons from the network. An example for a real spatio-temporal system identification problem is presented to demonstrate the performance of the proposed new modeling framework.

Neighborhood detection and local state vector construction for the identification of spatiotemporal systems is considered in this paper. Determining the neighborhood size both in the space and time domain can considerably reduce the complexity of the set of candidate model terms for the identification of coupled map lattice models. The computation requirements of the model identification algorithm can also be greatly reduced instead of the more direct identification approach of searching over the entire spatiotemporal neighborhood in the original space. In this paper, a new neighborhood detection method is introduced based on embedding theory for nonlinear dynamical systems to produce an initial spatiotemporal neighborhood for the identification of spatiotemporal systems. Numerical examples are provided to demonstrate the feasibility and applicability of the new neighborhood detection method.

Agent-based models are widely used for the simulation of systems from several domains (biology, economics, meteorology, etc). In biology agent-based models are very useful for predicting the social behaviour of systems; in particular they seem well adapted to model the behaviour of a cell population. In this paper an agent-based model, developed to study normal human keratinocytes (tissue cells), will be investigated. This kind of model exhibits probabilistic behaviour and the validation of simulation results is often done with a qualitative analysis by the experts (biologists). The main objective of this paper is to propose new variables and metrics that allow the comparison and a possible quantitative validation using numerical results from simulations.

In this work, the problem of metabolic flux estimation is formulated as a problem of parameter estimation from incomplete labelling data. The expectation/conditional maximisation (ECM) algorithm is used to determined a maximum-likelihood (ML) estimate because of its simplicity and stable convergence. We propose to simplify a nonlinear inverse problem, generally numerically solved by an iterative optimisation algorithm, to a linear regression problem which is arrived at from a linear-in-the-parameter formulation during a partial optimisation process of the ECM algorithm. Three linear least square algorithms, the ordinary least squares (LS), the total least squares (TLS) and the constrained least squares (CLS), have been tested to solve the linear regression in this step. Using simulations, resulting parameter estimates and errors in flux estimation are compared and evaluated. The performance of the algorithms are investigated under two scenarios; when the labelling data are corrupted by a wide range of noise and when the labelling data are incompletely observed. Results suggest that the estimates from the ECM algorithm using CLS produce results superior to other combinations and have potential to be refined to improve its performance in metabolic flux estimation

The quantitative comprehension of a metabolic system in its dynamic state is a prerequisite for purposed strain improvement and enzymatic regulation. It is therefore crucial to accurately obtain the extracellular and intracellular metabolite concentrations in vivo in the time scale faster than typical metabolite turn-over rate. Though intracellular metabolite dynamics are addressable by latest rapid sampling technology, the measurements are not satisfactory due to the low percentage of intracellular volume to the total sample volume and often the low concentration levels of most intracellular metabolites. When the examined system is observable, a possible solution to this problem is by means of available statistical estimation approach. Hence, in this paper, the sequential Monte Carlo filter is applied to estimate the intracellular metabolite concentrations with the knowledge of extracellular metabolite concentrations. The application of this algorithm in a synthetic system with simulated data illustrates the applicability of this approach. All the intracellular metabolite concentrations are accurately estimated and the extracellular states are reconstructed from their noisy measurements. The dynamic flux distributions are also obtained and their underlying biological meanings are described

Increasingly, personalised robots - robots especially designed and programmed for an individual's needs and preferences - are being used to support humans in their daily lives, most notably in the area of service robotics. Arguably, the closer the robot is programmed to the individual's needs, the more useful it is, and we believe that giving people the opportunity to program their own robots, rather than programming robots for them, will push robotics research one step further in the personalised robotics field. However, traditional robot programming techniques require specialised technical skills from different disciplines and it is not reasonable to expect end-users to have these skills. In this paper, we therefore present a new method of obtaining robot control code - programming by demonstration through system identification - which algorithmically and automatically transfers human behaviours into robot control code, using transparent, analysable mathematical functions. Besides providing a simple means of generating perception-action mappings, they have the additional advantage that can also be used to form hypotheses and theoretical analysis of robot behaviour. We demonstrate the viability of this approach by teaching a Scitos G5 mobile robot to achieve wall following and corridor passing behaviours.

A new unsupervised forward orthogonal search (FOS) algorithm is introduced for feature selection and ranking. In the new algorithm, features are selected in a stepwise way, one at a time, by estimating the capability of each specified candidate feature subset to represent the overall features in the measurement space. A squared correlation function is employed as the criterion to measure the dependency between features and this makes the new algorithm easy to implement. The forward orthogonalization strategy, which combines good effectiveness with high efficiency, enables the new algorithm to produce efficient feature subsets with a clear physical interpretation.

Metabolic flux analysis is important for metabolic system regulation and intracellular pathway identification. A popular approach for intracellular flux estimation involves using 13C tracer experiments to label states that can be measured by nuclear magnetic resonance spectrometry or gas chromatography mass spectrometry. However, the bilinear balance equations derived from 13C tracer experiments and the noisy measurements require a nonlinear optimization approach to obtain the optimal solution. In this paper, the flux quantification problem is formulated as an error-minimization problem with equality and inequality constraints through the 13C balance and stoichiometric equations. The stoichiometric constraints are transformed to a null space by singular value decomposition. Self-adaptive evolutionary algorithms are then introduced for flux quantification. The performance of the evolutionary algorithm is compared with ordinary least squares estimation by the simulation of the central pentose phosphate pathway. The proposed algorithm is also applied to the central metabolism of Corynebacterium glutamicum under lysine-producing conditions. A comparison between the results from the proposed algorithm and data from the literature is given. The complexity of a metabolic system with bidirectional reactions is also investigated by analyzing the fluctuations in the flux estimates when available measurements are varied.

A sparse representation, with satisfactory approximation accuracy, is usually desirable in any nonlinear system identification and signal processing problem. A new forward orthogonal regression algorithm, with mutual information interference, is proposed for sparse model selection and parameter estimation. The new algorithm can be used to construct parsimonious linear-in-the-parameters models.

MOTIVATION: Metabolic flux analysis via a (13)C tracer experiment has been achieved using a Monte Carlo method with the assumption of system noise as Gaussian noise. However, an unbiased flux analysis requires the estimation of fluxes and metabolites jointly without the restriction on the assumption of Gaussian noise. The flux distributions under such a framework can be freely obtained with various system noise and uncertainty models. RESULTS: In this paper, a stochastic generative model of the metabolic system is developed. Following this, the Markov Chain Monte Carlo (MCMC) approach is applied to flux distribution analysis. The disturbances and uncertainties in the system are simplified as truncated Gaussian multiplicative models. The performance in a real metabolic system is illustrated by the application to the central metabolism of Corynebacterium glutamicum. The flux distributions are illustrated and analyzed in order to understand the underlying flux activities in the system. AVAILABILITY: Algorithms are available upon request.

Extracting the rules from spatio-temporal patterns generated by the evolution of cellular automata (CA) usually requires a priori information about the observed system, but in many applications little information will be known about the pattern. This paper introduces a new neighborhood detection algorithm which can determine the range of the neighborhood without any knowledge of the system by introducing a criterion based on mutual information (and an indication of over-estimation). A coarse-to-fine identification routine is then proposed to determine the CA rule from the observed pattern. Examples, including data from a real experiment, are employed to evaluate the new algorithm.

A new class of wavelet networks (WNs) is proposed for nonlinear system identification. In the new networks, the model structure for a high-dimensional system is chosen to be a superimposition of a number of functions with fewer variables. By expanding each function using truncated wavelet decompositions, the multivariate nonlinear networks can be converted into linear-in-the-parameter regressions, which can be solved using least-squares type methods. An efficient model term selection approach based upon a forward orthogonal least squares (OLS) algorithm and the error reduction ratio (ERR) is applied to solve the linear-in-the-parameters problem in the present study. The main advantage of the new WN is that it exploits the attractive features of multiscale wavelet decompositions and the capability of traditional neural networks. By adopting the analysis of variance (ANOVA) expansion, WNs can now handle nonlinear identification problems in high dimensions.

Metabolic fluxes have been regarded as an important quantity for metabolic engineering as they reveal cause-effect relationships between genetic modifications and resulting changes in metabolic activity and are used as a prerequisite for the design of optimal whole cell biocatalysts. The intracellular fluxes must be estimated due to the inability to measure them directly. A particular useful technique involves the use of /sup 13/C-enriched substrates and the measurement of label distribution generated for each intermediate to uncover all unmeasured fluxes by solving the label balance equations, e.g. isotopomer balances, at steady state. However, the formation of these equations typically requires tedious algebraic manipulation and in many cases the resulting equations must be solved numerically, due to the nonlinearity and high dimensionality. Here we present three different evolutionary algorithm (EA) based approaches in combination with the least squares algorithm to show the applicability of EAs in metabolic flux quantification. The performance of the algorithms are illustrated and discussed through the simulation of the cyclic pentose phosphate network in a noisy environment and the identifiability problem is also considered.

The identification of probabilistic cellular automata (PCA) is studied using a new two stage neighborhood detection algorithm. It is shown that a binary probabilistic cellular automaton (BPCA) can be described by an integer-parameterized polynomial corrupted by noise. Searching for the correct neighborhood of a BPCA is then equivalent to selecting the correct terms which constitute the polynomial model of the BPCA, from a large initial term set. It is proved that the contribution values for the correct terms can be calculated independently of the contribution values for the noise terms. This allows the neighborhood detection technique developed for deterministic rules in to be applied with a larger cutoff value to discard the majority of spurious terms and to produce an initial presearch for the BPCA neighborhood. A multiobjective genetic algorithm (GA) search with integer constraints is then evolved to refine the reduced neighborhood and to identify the polynomial rule which is equivalent to the probabilistic rule with the largest probability. A probability table representing the BPCA can then be determined based on the identified neighborhood and the deterministic rule. The new algorithm is tested over a large set of one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) BPCA rules. Simulation results demonstrate the efficiency of the new method.

Extracting the rules from spatio-temporal patterns generated by the evolution of cellular automata (CA) usually produces a CA rule table without providing a clear understanding of the structure of the neighborhood or the CA rule. In this paper, a new identification method based on using a modified orthogonal least squares or CA-OLS algorithm to detect the neighborhood structure and the underlying polynomial form of the CA rules is proposed. The Quine-McCluskey method is then applied to extract minimum Boolean expressions from the polynomials. Spatio-temporal patterns produced by the evolution of 1D, 2D, and higher dimensional binary CAs are used to illustrate the new algorithm, and simulation results show that the CA-OLS algorithm can quickly select both the correct neighborhood structure and the corresponding rule.

An alternative solution to the model structure selection problem is introduced by conducting a forward search through the many possible candidate model terms initially and then performing an exhaustive all subset model selection on the resulting model. An example is included to demonstrate that this approach leads to dynamically valid nonlinear models.

A multiobjective genetic algorithm (GA) is introduced to identify both the neighborhood and the rule set in the form of a parsimonious Boolean expression for both one- and two-dimensional cellular automata (CA). Simulation results illustrate that the new algorithm performs well even when the patterns are corrupted by static and dynamic noise.

Using genetic algorithms (GAs) to search for cellular automation (CA) rules from spatio-temporal patterns produced in CA evolution is usually complicated and time-consuming when both, the neighborhood structure and the local rule are searched simultaneously. The complexity of this problem motivates the development of a new search which separates the neighborhood detection from the GA search. In the paper, the neighborhood is determined by independently selecting terms from a large term set on the basis of the contribution each term makes to the next state of the cell to be updated. The GA search is then started with a considerably smaller set of candidate rules pre-defined by the detected neighhorhood. This approach is tested over a large set of one-dimensional (1-D) and two-dimensional (2-D) CA rules. Simulation results illustrate the efficiency of the new algorithm.

This paper is concerned with the adaptive control of continuous-time nonlinear dynamical systems using neural networks. A novel neural network architecture, referred to as a variable neural network, is proposed and shown to be useful in approximating the unknown nonlinearities of dynamical systems. In the variable neural networks, the number of basis functions can be either increased or decreased with time, according to specified design strategies, so that the network will not overfit or underfit the data set. Based on the Gaussian radial basis function (GRBF) variable neural network, an adaptive control scheme is presented. The location of the centers and the determination of the widths of the GRBFs in the variable neural network are analyzed to make a compromise between orthogonality and smoothness. The weight-adaptive laws developed using the Lyapunov synthesis approach guarantee the stability of the overall control scheme, even in the presence of modeling error(s). The tracking errors converge to the required accuracy through the adaptive control algorithm derived by combining the variable neural network and Lyapunov synthesis techniques. The operation of an adaptive control scheme using the variable neural network is demonstrated using two simulated examples.