Shinn-Jang Ho

Predicting and analyzing DNA-binding domains using a systematic approach to identifying a set of informative physicochemical and biochemical properties

BackgroundExisting methods of predicting DNA-binding proteins used valuable features of physicochemical properties to design support vector machine (SVM) based classifiers. Generally, selection of physicochemical properties and determination of their corresponding feature vectors rely mainly on known properties of binding mechanism and experience of designers. However, there exists a troublesome problem for designers that some different physicochemical properties have similar vectors of representing 20 amino acids and some closely related physicochemical properties have dissimilar vectors.ResultsThis study proposes a systematic approach (named Auto-IDPCPs) to automatically identify a set of physicochemical and biochemical properties in the AAindex database to design SVM-based classifiers for predicting and analyzing DNA-binding domains/proteins. Auto-IDPCPs consists of 1) clustering 531 amino acid indices in AAindex into 20 clusters using a fuzzy c-means algorithm, 2) utilizing an efficient genetic algorithm based optimization method IBCGA to select an informative feature set of size m to represent sequences, and 3) analyzing the selected features to identify related physicochemical properties which may affect the binding mechanism of DNA-binding domains/proteins. The proposed Auto-IDPCPs identified m=22 features of properties belonging to five clusters for predicting DNA-binding domains with a five-fold cross-validation accuracy of 87.12%, which is promising compared with the accuracy of 86.62% of the existing method PSSM-400. For predicting DNA-binding sequences, the accuracy of 75.50% was obtained using m=28 features, where PSSM-400 has an accuracy of 74.22%. Auto-IDPCPs and PSSM-400 have accuracies of 80.73% and 82.81%, respectively, applied to an independent test data set of DNA-binding domains. Some typical physicochemical properties discovered are hydrophobicity, secondary structure, charge, solvent accessibility, polarity, flexibility, normalized Van Der Waals volume, pK (pK-C, pK-N, pK-COOH and pK-a(RCOOH)), etc.ConclusionsThe proposed approach Auto-IDPCPs would help designers to investigate informative physicochemical and biochemical properties by considering both prediction accuracy and analysis of binding mechanism simultaneously. The approach Auto-IDPCPs can be also applicable to predict and analyze other protein functions from sequences.

Optimizing fuzzy neural networks for tuning PID controllers using an orthogonal simulated annealing algorithm OSA

In this paper, we formulate an optimization problem of establishing a fuzzy neural network model (FNNM) for efficiently tuning proportional-integral-derivative (PID) controllers of various test plants with under-damped responses using a large number P of training plants such that the mean tracking error J of the obtained P control systems is minimized. The FNNM consists of four fuzzy neural networks (FNNs) where each FNN models one of controller parameters (K, T/sub i/, T/sub d/, and b) of PID controllers. An existing indirect, two-stage approach used a dominant pole assignment method with P=198 to find the corresponding PID controllers. Consequently, an adaptive neuro-fuzzy inference system (ANFIS) is used to independently train the four individual FNNs using input the selected 176 of the 198 PID controllers that 22 controllers with parameters having large variation are abandoned. The innovation of the proposed approach is to directly and simultaneously optimize the four FNNs by using a novel orthogonal simulated annealing algorithm (OSA). High performance of the OSA-based approach arises from that OSA can effectively optimize lots of parameters of the FNNM to minimize J. It is shown that the OSA-based FNNM with P=176 can improve the ANFIS-based FNNM in averagely decreasing 13.08% error J and 88.07% tracking error of the 22 test plants by refining the solution of the ANFIS-based method. Furthermore, the OSA-based FNNMs using P=198 and 396 from an extensive tuning domain have similar good performance with that using P=176 in terms of J.

A Novel Intelligent Multiobjective Simulated Annealing Algorithm for Designing Robust PID Controllers

This paper proposes an intelligent multiobjective simulated annealing algorithm (IMOSA) and its application to an optimal proportional integral derivative (PID) controller design problem. A well-designed PID-type controller should satisfy the following objectives: 1) disturbance attenuation; 2) robust stability; and 3) accurate setpoint tracking. The optimal PID controller design problem is a large-scale multiobjective optimization problem characterized by the following: 1) nonlinear multimodal search space; 2) large-scale search space; 3) three tight constraints; 4) multiple objectives; and 5) expensive objective function evaluations. In contrast to existing multiobjective algorithms of simulated annealing, the high performance in IMOSA arises mainly from a novel multiobjective generation mechanism using a Pareto-based scoring function without using heuristics. The multiobjective generation mechanism operates on a high-score nondominated solution using a systematic reasoning method based on an orthogonal experimental design, which exploits its neighborhood to economically generate a set of well-distributed nondominated solutions by considering individual and overall objectives. IMOSA is evaluated by using a practical design example of a super-maneuverable fighter aircraft system. An efficient existing multiobjective algorithm, the improved strength Pareto evolutionary algorithm, is also applied to the same example for comparison. Simulation results demonstrate high performance of the IMOSA-based method in designing robust PID controllers.

Designing structure-specified mixed H/sub 2//H/sub /spl infin// optimal controllers using an intelligent genetic algorithm IGA

This brief proposes an efficient method for designing accurate structure-specified mixed H/sub 2//H/sub /spl infin// optimal controllers for systems with uncertainties and disturbance using an intelligent genetic algorithm (IGA). The newly-developed IGA with intelligent crossover based on orthogonal experimental design (OED) is efficient for solving intractable engineering problems with lots of design parameters. The IGA-based method without using prior domain knowledge can efficiently solve design problems of multi-input-multi-output (MIMO) optimal control systems, which is very suitable for practical engineering designs. High performance and validity of the proposed method are evaluated by two test problems, a MIMO distillation column model and a MIMO super maneuverable F18/HARV fighter aircraft system. It is shown empirically that the IGA-based method has good tracking performance, robust stability and disturbance attenuation for both controllers, compared with the existing methods.

Prediction and analysis of protein solubility using a novel scoring card method with dipeptide composition.

BackgroundExisting methods for predicting protein solubility on overexpression in Escherichia coli advance performance by using ensemble classifiers such as two-stage support vector machine (SVM) based classifiers and a number of feature types such as physicochemical properties, amino acid and dipeptide composition, accompanied with feature selection. It is desirable to develop a simple and easily interpretable method for predicting protein solubility, compared to existing complex SVM-based methods.ResultsThis study proposes a novel scoring card method (SCM) by using dipeptide composition only to estimate solubility scores of sequences for predicting protein solubility. SCM calculates the propensities of 400 individual dipeptides to be soluble using statistic discrimination between soluble and insoluble proteins of a training data set. Consequently, the propensity scores of all dipeptides are further optimized using an intelligent genetic algorithm. The solubility score of a sequence is determined by the weighted sum of all propensity scores and dipeptide composition. To evaluate SCM by performance comparisons, four data sets with different sizes and variation degrees of experimental conditions were used. The results show that the simple method SCM with interpretable propensities of dipeptides has promising performance, compared with existing SVM-based ensemble methods with a number of feature types. Furthermore, the propensities of dipeptides and solubility scores of sequences can provide insights to protein solubility. For example, the analysis of dipeptide scores shows high propensity of α-helix structure and thermophilic proteins to be soluble.ConclusionsThe propensities of individual dipeptides to be soluble are varied for proteins under altered experimental conditions. For accurately predicting protein solubility using SCM, it is better to customize the score card of dipeptide propensities by using a training data set under the same specified experimental conditions. The proposed method SCM with solubility scores and dipeptide propensities can be easily applied to the protein function prediction problems that dipeptide composition features play an important role.AvailabilityThe used datasets, source codes of SCM, and supplementary files are available at http://iclab.life.nctu.edu.tw/SCM/.

Intelligent particle swarm optimization in multi-objective problems

In this paper, we proposes a novel intelligent multi-objective particle swarm optimization (IMOPSO) to solve multi-objective optimization problems. High performance of IMOPSO mainly arises from two parts: one is using generalized Pareto-based scale-independent fitness function (GPSISF) can efficiently given all candidate solutions a score, and then decided candidate solutions level. The other one is replacing the conventional particle move process of PSO with an intelligent move mechanism (IMM) based on orthogonal experimental design to enhance the search ability. IMM can evenly sample and analyze from the best experience of an individual particle and group particles by using a systematic reasoning method, and then efficiently generate a good candidate solution for the next move of the particle. Some benchmark functions are used to evaluate the performance of IMOPSO, and compared with some existing multi-objective evolution algorithms. According to experimental results and analysis, they show that IMOPSO performs well.

Prediction of non-classical secreted proteins using informative physicochemical properties

The prediction of non-classical secreted proteins is a significant problem for drug discovery and development of disease diagnosis. The characteristic of non-classical secreted proteins is they are leaderless proteins without signal peptides in N-terminal. This characteristic makes the prediction of non-classical proteins more difficult and complicated than the classical secreted proteins. We identify a set of informative physicochemical properties of amino acid indices cooperated with support vector machine (SVM) to find discrimination between secreted and non-secreted proteins and to predict non-classical secreted proteins. When the sequence identity of dataset was reduced to 25%, the prediction accuracy on training dataset is 85% which is much better than the traditional sequence similarity-based BLAST or PSI-BLAST tool. The accuracy of independent test is 82%. The most effective features of prediction revealed the fundamental differences of physicochemical properties between secreted and non-secreted proteins. The interpretable and valuable information could be beneficial for drug discovery or the development of new blood biochemical examinations.

A Novel Multi-objective Orthogonal Simulated Annealing Algorithm for Solving Multi-objective Optimization Problems with a Large Number of Parameters

In this paper, a novel multi-objective orthogonal simulated annealing algorithm MOOSA using a generalized Pareto-based scale-independent fitness function and multi-objective intelligent generation mechanism (MOIGM) is proposed to efficiently solve multi-objective optimization problems with large parameters. Instead of generate-and-test methods, MOIGM makes use of a systematic reasoning ability of orthogonal experimental design to efficiently search for a set of Pareto solutions. It is shown empirically that MOOSA is comparable to some existing population-based algorithms in solving some multi-objective test functions with a large number of parameters.

Prediction of mouse senescence from HE-Stain liver images using an ensemble SVM classifier

Study of cellular senescence from images in molecular level plays an important role in understanding the molecular basis of ageing. It is desirable to know the morphological variation between young and senescent cells. This study proposes an ensemble support vector machine (SVM) based classifier with a novel set of image features to predict mouse senescence from HE-stain liver images categorized into four classes. For the across-subject prediction that all images of the same mouse are divided into training and test images, the test accuracy is as high as 97.01% by selecting an optimal set of informative image features using an intelligent genetic algorithm. For the leave-one-subject-out prediction that the test mouse is not involved in the training images of 20 mice, we identified eight informative feature sets and established eight SVM classifiers with a single feature set. The best accuracy of using an SVM classifier is 71.73% and the ensemble classifier consisting of these eight SVM classifiers can advance performance with accuracy of 80.95%. The best two feature sets are the gray level correlation matrix for describing texture and Haralick texture set, which are good morphological features in studying cellular senescence.

Inferring S-system models of genetic networks from a time-series real data set of gene expression profiles

It is desirable to infer cellular dynamic regulation networks from gene expression profiles to discover more delicate and substantial functions in molecular biology, biochemistry, bioengineering, and pharmaceutics. The S-system model is suitable to characterize biochemical network systems and capable of analyzing the regulatory system dynamics. To cope with the problem ldquomultiplicity of solutionsrdquo, a sufficient amount of data sets of time-series gene expression profiles were often used. An efficient newly-developed method iTEA was proposed to effectively obtain S-system models from a large number (e.g., 15) of simulated data sets with/without noise. In this study, we propose an extended optimization method (named iTEAP) based on iTEA to infer the S-system models of genetic networks from a time-series real data set of gene expression profiles (using SOS DNA microarray data in E. coli as an example). The algorithm iTEAP generated additionally multiple data sets of gene expression profiles by perturbing the given data set. The results reveal that 1) iTEAP can obtain S-system models with high-quality profiles to best fit the observed profiles; 2) the performance of using multiple data sets is better than that of using a single data set in terms of solution quality, and 3) the effectiveness of iTEAP using a single data set is close to that of iTEA using two real data sets.