17815381
SCPRED: Accurate prediction of protein structural class for sequences of twilight-zone similarity with predicting sequences
BackgroundProtein structure prediction methods provide accurate results when a homologous protein is predicted, while poorer predictions are obtained in the absence of homologous templates. However, some protein chains that share twilight-zone pairwise identity can form similar folds and thus determining structural similarity without the sequence similarity would be desirable for the structure prediction. The folding type of a protein or its domain is defined as the structural class. Current structural class prediction methods that predict the four structural classes defined in SCOP provide up to 63% accuracy for the datasets in which sequence identity of any pair of sequences belongs to the twilight-zone. We propose SCPRED method that improves prediction accuracy for sequences that share twilight-zone pairwise similarity with sequences used for the prediction.ResultsSCPRED uses a support vector machine classifier that takes several custom-designed features as its input to predict the structural classes. Based on extensive design that considers over 2300 index-, composition- and physicochemical properties-based features along with features based on the predicted secondary structure and content, the classifier's input includes 8 features based on information extracted from the secondary structure predicted with PSI-PRED and one feature computed from the sequence. Tests performed with datasets of 1673 protein chains, in which any pair of sequences shares twilight-zone similarity, show that SCPRED obtains 80.3% accuracy when predicting the four SCOP-defined structural classes, which is superior when compared with over a dozen recent competing methods that are based on support vector machine, logistic regression, and ensemble of classifiers predictors.ConclusionThe SCPRED can accurately find similar structures for sequences that share low identity with sequence used for the prediction. The high predictive accuracy achieved by SCPRED is attributed to the design of the features, which are capable of separating the structural classes in spite of their low dimensionality. We also demonstrate that the SCPRED's predictions can be successfully used as a post-processing filter to improve performance of modern fold classification methods.
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
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.
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.
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.
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.
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.
41845464
Advances in Natural Computation, First International Conference, ICNC 2005, Changsha, China, August 27-29, 2005, Proceedings, Part I
52833236
Boosting Input/Output Hidden Markov Models for Sequence Classification
Input/output hidden Markov model (IOHMM) has turned out to be effective in sequential data processing via supervised learning. However, there are several difficulties, e.g. model selection, unexpected local optima and high computational complexity, which hinder an IOHMM from yielding the satisfactory performance in sequence classification. Unlike previous efforts, this paper presents an ensemble learning approach to tackle the aforementioned problems of the IOHMM. As a result, simple IOHMMs of different topological structures are used as base learners in our boosting algorithm and thus an ensemble of simple IOHMMs tend to tackle a complicated sequence classification problem without the need of explicit model selection. Simulation results in text-dependent speaker identification demonstrate the effectiveness of boosted IOHMMs for sequence classification.
1262783
An Immunity-Based Intrusion Detection Solution for Database Systems
Database intrusion detection has been an important research area in database security. It focuses on malicious transaction attacks, which cannot be handled by traditional database security mechanisms, such as authorization, access control, integrity control, and so on. Although there have appeared some intrusion detection systems, current researches on malicious transaction detection are limited in accuracy and efficiency. Inspired by natural immune system, we propose a novel immunity-based intrusion detection solution for database system in this paper. It provides an additional layer of defense against DBMS misuse, especially malicious transactions. The ability to learn and to adapt to the environment dynamically entitles the system to detect both known and unknown malicious transaction intrusions efficiently. Simulations show that the database intrusion detection system based on data immunity can accelerate detection of malicious transaction attacks and improve its accuracy without causing any other performance penalty.
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