13931461
Accurate sequence-based prediction of catalytic residues
MOTIVATION
Prediction of catalytic residues provides useful information for the research on function of enzymes. Most of the existing prediction methods are based on structural information, which limits their use. We propose a sequence-based catalytic residue predictor that provides predictions with quality comparable to modern structure-based methods and that exceeds quality of state-of-the-art sequence-based methods.


RESULTS
Our method (CRpred) uses sequence-based features and the sequence-derived PSI-BLAST profile. We used feature selection to reduce the dimensionality of the input (and explain the input) to support vector machine (SVM) classifier that provides predictions. Tests on eight datasets and side-by-side comparison with six modern structure- and sequence-based predictors show that CRpred provides predictions with quality comparable to current structure-based methods and better than sequence-based methods. The proposed method obtains 15-19% precision and 48-58% TP (true positive) rate, depending on the dataset used. CRpred also provides confidence values that allow selecting a subset of predictions with higher precision. The improved quality is due to newly designed features and careful parameterization of the SVM. The features incorporate amino acids characterized by the highest and the lowest propensities to constitute catalytic residues, Gly that provides flexibility for catalytic sites and sequence motifs characteristic to certain catalytic reactions. Our features indicate that catalytic residues are on average more conserved when compared with the general population of residues and that highly conserved amino acids characterized by high catalytic propensity are likely to form catalytic sites. We also show that local (with respect to the sequence) hydrophobicity contributes towards the prediction.
3658125
PFRES: protein fold classification by using evolutionary information and predicted secondary structure
MOTIVATION
The number of protein families has been estimated to be as small as 1000. Recent study shows that the growth in discovery of novel structures that are deposited into PDB and the related rate of increase of SCOP categories are slowing down. This indicates that the protein structure space will be soon covered and thus we may be able to derive most of remaining structures by using the known folding patterns. Present tertiary structure prediction methods behave well when a homologous structure is predicted, but give poorer results when no homologous templates are available. At the same time, some proteins that share twilight-zone sequence identity can form similar folds. Therefore, determination of structural similarity without sequence similarity would be beneficial for prediction of tertiary structures.


RESULTS
The proposed PFRES method for automated protein fold classification from low identity (<35%) sequences obtains 66.4% and 68.4% accuracy for two test sets, respectively. PFRES obtains 6.3-12.4% higher accuracy than the existing methods. The prediction accuracy of PFRES is shown to be statistically significantly better than the accuracy of competing methods. Our method adopts a carefully designed, ensemble-based classifier, and a novel, compact and custom-designed feature representation that includes nearly 90% less features than the representation of the most accurate competing method (36 versus 283). The proposed representation combines evolutionary information by using the PSI-BLAST profile-based composition vector and information extracted from the secondary structure predicted with PSI-PRED.


AVAILABILITY
The method is freely available from the authors upon request.
15411856
Prediction of the Number of Helices for the Twilight Zone Proteins
Protein structure prediction is one of the core research areas in bioinformatics. This paper addresses the protein secondary structure prediction problem for the twilight zone proteins, which are characterized by low, about 25% homology to the sets of known sequences. The commonly used sequence alignment based algorithms fail to provide accurate prediction for sequences of such low homology, and thus alternative solutions should be sought. We propose a novel method that aims at the prediction of the number of helical structures based on the twilight zone protein sequences. The method is based on a custom designed and compact feature based sequences representation and applies a decision tree prediction algorithm. The performed experimental study shows superiority of the proposed method over three other prediction algorithms and the results provided by YASPIN algorithm, which is a state-of-the-art alignment based secondary structure prediction method designed using low homology sequences
13249966
Prediction of integral membrane protein type by collocated hydrophobic amino acid pairs
A computational model, IMP-TYPE, is proposed for the classification of five types of integral membrane proteins from protein sequence. The proposed model aims not only at providing accurate predictions but most importantly it incorporates interesting and transparent biological patterns. When contrasted with the best-performing existing models, IMP-TYPE reduces the error rates of these methods by 19 and 34% for two out-of-sample tests performed on benchmark datasets. Our empirical evaluations also show that the proposed method provides even bigger improvements, i.e., 29 and 45% error rate reductions, when predictions are performed for sequences that share low (40%) identity with sequences from the training dataset. We also show that IMP-TYPE can be used in a standalone mode, i.e., it duplicates significant majority of correct predictions provided by other leading methods, while providing additional correct predictions which are incorrectly classified by the other methods. Our method computes predictions using a Support Vector Machine classifier that takes feature-based encoded sequence as its input. The input feature set includes hydrophobic AA pairs, which were selected by utilizing a consensus of three feature selection algorithms. The hydrophobic residues that build up the AA pairs used by our method are shown to be associated with the formation of transmembrane helices in a few recent studies concerning integral membrane proteins. Our study also indicates that Met and Phe display a certain degree of hydrophobicity, which may be more crucial than their polarity or aromaticity when they occur in the transmembrane segments. This conclusion is supported by a recent study on potential of mean force for membrane protein folding and a study of scales for membrane propensity of amino acids.
193129
Sequence based residue depth prediction using evolutionary information and predicted secondary structure
BackgroundResidue depth allows determining how deeply a given residue is buried, in contrast to the solvent accessibility that differentiates between buried and solvent-exposed residues. When compared with the solvent accessibility, the depth allows studying deep-level structures and functional sites, and formation of the protein folding nucleus. Accurate prediction of residue depth would provide valuable information for fold recognition, prediction of functional sites, and protein design.ResultsA new method, RDPred, for the real-value depth prediction from protein sequence is proposed. RDPred combines information extracted from the sequence, PSI-BLAST scoring matrices, and secondary structure predicted with PSIPRED. Three-fold/ten-fold cross validation based tests performed on three independent, low-identity datasets show that the distance based depth (computed using MSMS) predicted by RDPred is characterized by 0.67/0.67, 0.66/0.67, and 0.64/0.65 correlation with the actual depth, by the mean absolute errors equal 0.56/0.56, 0.61/0.60, and 0.58/0.57, and by the mean relative errors equal 17.0%/16.9%, 18.2%/18.1%, and 17.7%/17.6%, respectively. The mean absolute and the mean relative errors are shown to be statistically significantly better when compared with a method recently proposed by Yuan and Wang [Proteins 2008; 70:509–516]. The results show that three-fold cross validation underestimates the variability of the prediction quality when compared with the results based on the ten-fold cross validation. We also show that the hydrophilic and flexible residues are predicted more accurately than hydrophobic and rigid residues. Similarly, the charged residues that include Lys, Glu, Asp, and Arg are the most accurately predicted. Our analysis reveals that evolutionary information encoded using PSSM is characterized by stronger correlation with the depth for hydrophilic amino acids (AAs) and aliphatic AAs when compared with hydrophobic AAs and aromatic AAs. Finally, we show that the secondary structure of coils and strands is useful in depth prediction, in contrast to helices that have relatively uniform distribution over the protein depth. Application of the predicted residue depth to prediction of buried/exposed residues shows consistent improvements in detection rates of both buried and exposed residues when compared with the competing method. Finally, we contrasted the prediction performance among distance based (MSMS and DPX) and volume based (SADIC) depth definitions. We found that the distance based indices are harder to predict due to the more complex nature of the corresponding depth profiles.ConclusionThe proposed method, RDPred, provides statistically significantly better predictions of residue depth when compared with the competing method. The predicted depth can be used to provide improved prediction of both buried and exposed residues. The prediction of exposed residues has implications in characterization/prediction of interactions with ligands and other proteins, while the prediction of buried residues could be used in the context of folding predictions and simulations.
2074142
Prediction of protein structural class using novel evolutionary collocation-based sequence representation
Knowledge of structural classes is useful in understanding of folding patterns in proteins. Although existing structural class prediction methods applied virtually all state-of-the-art classifiers, many of them use a relatively simple protein sequence representation that often includes amino acid (AA) composition. To this end, we propose a novel sequence representation that incorporates evolutionary information encoded using PSI-BLAST profile-based collocation of AA pairs. We used six benchmark datasets and five representative classifiers to quantify and compare the quality of the structural class prediction with the proposed representation. The best, classifier support vector machine achieved 61-96% accuracy on the six datasets. These predictions were comprehensively compared with a wide range of recently proposed methods for prediction of structural classes. Our comprehensive comparison shows superiority of the proposed representation, which results in error rate reductions that range between 14% and 26% when compared with predictions of the best-performing, previously published classifiers on the considered datasets. The study also shows that, for the benchmark dataset that includes sequences characterized by low identity (i.e., 25%, 30%, and 40%), the prediction accuracies are 20-35% lower than for the other three datasets that include sequences with a higher degree of similarity. In conclusion, the proposed representation is shown to substantially improve the accuracy of the structural class prediction. A web server that implements the presented prediction method is freely available at http://biomine.ece.ualberta.ca/Structural_Class/SCEC.html.
7013408
Towards better making a decision in speaker verification
Speaker verification is a process that accepts or rejects the identity claim of a speaker. How to make a decision is a critical problem; a threshold for decision-making critically determines performance of a speaker verification system. Traditional threshold estimation methods take only information conveyed by training data into consideration and, to a great extent, do not relate it to production data. It turns out that a speaker verification system with such threshold estimation suffers from poor performance in reality due to mismatches. In this paper, we propose several methods towards better decision-making in a practical speaker verification system. Our methods include the use of additional reliable statistical information for threshold estimation, elimination of abnormal data for better estimation of underlying statistics, and on-line incremental threshold update. To evaluate the performance of our methods, we have done simulations based on a baseline system, Gaussian Mixture Model, in both text-dependent and text-independent modes. Comparative results show that in contrast to the recent threshold estimation methods our methods yield considerably better performance, especially on miscellaneous mismatch conditions, in terms of generalization. Thus our methods provide a promising way for real speaker verification applications.
16833900
Securely Sharing Data in Encrypted Databases
Collaborative design and application integration emphasize the demand for database security. Database encryption is widely adopted to ensure data privacy, which can prevent attacks from both outside intruders and inside malicious users. Current researches on this area are mainly focusing on encryption algorithms, key management and encryption efficiency. However, data sharing nature of database system is usually neglected. In this paper, we propose an access control model, 3S-RBAC, which enables data sharing while guaranteeing privacy. The model has many features: the novel concept of strong permission and weak permission; the hierarchy of database objects and keys; the permission and key inheritance; the binding of keys and permissions. Implementation in OSCAR Secure DBMS shows that the model is flexible, secure, practical, and can be integrated easily into existing enterprise applications
12726286
Fast Multilevel Algorithm for a Minimization Problem in Impulse Noise Removal
An effective 2-phase method for removing impulse noise was recently proposed. Its phase 1 identifies noisy pixel candidates by using median-type filters. Then in phase $2$, it restores only the noisy pixel candidates by some variational methods. The resulting method can handle salt-and-pepper noise and random-valued impulse noise at a level as high as 90% and 60%, respectively. The aim of this paper is to generalize a fast multilevel method for Gaussian denoising to solving the minimization problem arising in phase $2$ of the 2-phase method. The multilevel algorithm gives better images than standard optimization methods such as the Newton method or the conjugate gradient method. Also it can handle more general regularization functionals than the smooth ones previously considered. Supporting numerical experiments on two-dimensional gray-scale images are presented.
15986478
MATLAB Simulink Modeling and Simulation of Zhang Neural Network for Online Time-Varying Matrix Inversion
Recently, a special kind of recurrent neural networks (RNN) with implicit dynamics has been proposed by Zhang et al for online time-varying problems solving (such as time-varying matrix inversion). Such a neural-dynamic system is elegantly designed by defining a matrix-valued error function rather than the usual scalar-valued norm-based error function. Its computational error can be made decrease to zero globally and exponentially. For the final purpose of field programmable gate array (FPGA) and application-specific integrated circuit (ASIC) realization, we investigate in this paper the MATLAB Simulink modeling and simulative verification of such a Zhang neural network (ZNN). By using click-and-drag mouse operations, it is easier to model and simulate in comparison with MATLAB coding. Both convergence and robustness properties of such a ZNN model are analyzed, which substantiate the effectiveness of Zhang neural network on inverting the time-varying matrices.
11647155
Methods of Combining Multiple Classifiers with Different Features and Their Applications to Text-Independent Speaker Identification
In practical applications of pattern recognition, there are often different features extracted from raw data which needs recognizing. Methods of combining multiple classifiers with different features are viewed as a general problem in various application areas of pattern recognition. In this paper, a systematic investigation has been made and possible solutions are classified into three frameworks, i.e. linear opinion pools, winner-take-all and evidential reasoning. For combining multiple classifiers with different features, a novel method is presented in the framework of linear opinion pools and a modified training algorithm for associative switch is also proposed in the framework of winner-take-all. In the framework of evidential reasoning, several typical methods are briefly reviewed for use. All aforementioned methods have already been applied to text-independent speaker identification. The simulations show that results yielded by the methods described in this paper are better than not only the individual classifiers' but also ones obtained by combining multiple classifiers with the same feature. It indicates that the use of combining multiple classifiers with different features is an effective way to attack the problem of text-independent speaker identification.