Bayesian learning of sparse gene regulatory networks.

Differential equations (DEs) have been the most widespread formalism for gene regulatory network (GRN) modeling, as they offer natural interpretation of biological processes, easy elucidation of gene relationships, and the capability of using efficient parameter estimation methods. However, an important limitation of DEs is their requirement of O(d(2)) parameters where d is the number of genes modeled, which often causes over-parameterization for large d, leading to the over-fitting of data and dense parameter sets that are hard to interpret. This paper presents the first effort to address the over-parameterization problem by applying the sparse Bayesian learning (SBL) method to sparsify the GRN model of DEs. SBL operates on the parsimony principle, with the objective to reduce the number of effective parameters by driving the redundant parameters to zero. The resulting sparse parameter set offers three important advantages for GRN inference: first, the inferred GRNs are more plausible, since the biological counterparts are known to be sparse; second, gene relationships can be more easily elucidated from sparse sets than from dense sets; and third, the solutions become more optimal and consistent, due to the reduction in the volume of solution space. Experiments are conducted on the yeast Saccharomyces cerevisiae time-series gene expression data, in which known regulatory events related to the cell cycle G1/S phase are reliably reproduced.

A hybrid genetic algorithm and expectation maximization method for global gene trajectory clustering.

Clustering time-course gene expression data (gene trajectories) is an important step towards solving the complex problem of gene regulatory network modeling and discovery as it significantly reduces the dimensionality of the gene space required for analysis. Traditional clustering methods that perform hill-climbing from randomly initialized cluster centers are prone to produce inconsistent and sub-optimal cluster solutions over different runs. This paper introduces a novel method that hybridizes genetic algorithm (GA) and expectation maximization algorithms (EM) for clustering gene trajectories with the mixtures of multiple linear regression models (MLRs), with the objective of improving the global optimality and consistency of the clustering performance. The proposed method is applied to cluster the human fibroblasts and the yeast time-course gene expression data based on their trajectory similarities. It outperforms the standard EM method significantly in terms of both clustering accuracy and consistency. The biological implications of the improved clustering performance are demonstrated.

An intelligent controller for automated operation of sequencing batch reactors.

In this paper the results are presented of original research into the automatic and "intelligent" detection of breakpoints in Dissolved Oxygen (DO) profiles. The research has been based on a large body of data collected from laboratory SBRs operating on synthetic wastewater. Two different approaches were followed to identify the endpoints. The paper analyses and evaluates the results of automatic detection on the basis of geometric features in the DO profiles. This was followed by classification of the detected breakpoints using different soft computing techniques based on Neural Network (NN), Fuzzy Neural Network (FuNN) and Evolving Fuzzy Neural Network (EfuNN) software systems for breakpoint classification. A high rate of successful detection and classification was obtained with up to 96% of the decisions made correctly. In order to overcome the limitations of this system to adapt to dynamically changing process conditions, an intelligent control model was developed by a combination between an Evolving Fuzzy Neural Net (EfuNN) combined with a logic decision unit. This system has the ability to "learn on-the-fly" and adjust its response pattern in order to maintain a high rate of successful breakpoint detection under varying changing process conditions. This software system has been sucessfully embedded on a small programmable controller for integration into larger process control systems for the operation of SBR plants.

Evolving fuzzy neural networks for supervised/unsupervised online knowledge-based learning.

This paper introduces evolving fuzzy neural networks (EFuNNs) as a means for the implementation of the evolving connectionist systems (ECOS) paradigm that is aimed at building online, adaptive intelligent systems that have both their structure and functionality evolving in time. EFuNNs evolve their structure and parameter values through incremental, hybrid supervised/unsupervised, online learning. They can accommodate new input data, including new features, new classes, etc., through local element tuning. New connections and new neurons are created during the operation of the system. EFuNNs can learn spatial-temporal sequences in an adaptive way through one pass learning and automatically adapt their parameter values as they operate. Fuzzy or crisp rules can be inserted and extracted at any time of the EFuNN operation. The characteristics of EFuNNs are illustrated on several case study data sets for time series prediction and spoken word classification. Their performance is compared with traditional connectionist methods and systems. The applicability of EFuNNs as general purpose online learning machines, what concerns systems that learn from large databases, life-long learning systems, and online adaptive systems in different areas of engineering are discussed.

HyFIS: adaptive neuro-fuzzy inference systems and their application to nonlinear dynamical systems.

This paper proposes an adaptive neuro-fuzzy system, HyFIS (Hybrid neural Fuzzy Inference System), for building and optimising fuzzy models. The proposed model introduces the learning power of neural networks to fuzzy logic systems and provides linguistic meaning to the connectionist architectures. Heuristic fuzzy logic rules and input-output fuzzy membership functions can be optimally tuned from training examples by a hybrid learning scheme comprised of two phases: rule generation phase from data; and rule tuning phase using error backpropagation learning scheme for a neural fuzzy system. To illustrate the performance and applicability of the proposed neuro-fuzzy hybrid model, extensive simulation studies of nonlinear complex dynamic systems are carried out. The proposed method can be applied to an on-line incremental adaptive learning for the prediction and control of nonlinear dynamical systems. Two benchmark case studies are used to demonstrate that the proposed HyFIS system is a superior neuro-fuzzy modelling technique.