1589839
Optimization of the Sliding Window Size for Protein Structure Prediction
Sliding window based methods are relatively often applied in prediction of various aspects related to protein structure. Despite their wide spread use, researchers did not establish a standard related to the size of the window, i.e., window sizes ranging between 7 and 17 residues were used in the past. To this end, this paper performs a computational study based on a probabilistic approach that aims at finding an optimal sliding window size. The results shows that formation of helical structure can be affected by amino acids (AAs) that are up to 9 positions away in the sequence, while the formation of coils and strands can be affected by AAs that are up to 3 and 6 positions away, respectively. Overall, our results suggest that a sliding window with 19 residues is optimal for secondary structure prediction, while for a specific prediction tasks, such as prediction of p-strands, a smaller window size is sufficient. Finally, the 20 AAs are categorized into five groups based on their influence of formation of the secondary structure. The finding related to the optimal window size was confirmed based on an independent experimental study related to the prediction of secondary protein structure
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.
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.
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.
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.
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
14878951
The orienteering problem in the plane revisited
We consider the <i>orienteering problem</i>: Given a set <i>P</i> of <i>n</i> points in the plane, a starting point <i>r</i> ∈ <i>P</i>, and a length constraint <i>B</i>, one needs to find a tour starting at <i>r</i> that visits as many points of <i>P</i> as possible and of length not exceeding <i>B</i>. We present a (1−ε)-approximation algorithm for this problem that runs in <i>n</i><sup><i>O</i>(1/ε)</sup> time, and visits at least (1−ε)<i>k</i><sub>opt</sub> points of <i>P</i>, where <i>k</i><sub>opt</sub> is the number of points visited by the optimal solution. This is the first polynomial time approximation scheme (PTAS) for this problem. The algorithm also works in higher dimensions.
3182057
A method of combining multiple probabilistic classifiers through soft competition on different feature sets
Abstract A novel method is proposed for combining multiple probabilistic classifiers on different feature sets. In order to achieve the improved classification performance, a generalized finite mixture model is proposed as a linear combination scheme and implemented based on radial basis function networks. In the linear combination scheme, soft competition on different feature sets is adopted as an automatic feature rank mechanism so that different feature sets can be always simultaneously used in an optimal way to determine linear combination weights. For training the linear combination scheme, a learning algorithm is developed based on Expectation–Maximization (EM) algorithm. The proposed method has been applied to a typical real-world problem, viz., speaker identification, in which different feature sets often need consideration simultaneously for robustness. Simulation results show that the proposed method yields good performance in speaker identification.
21847139
An Analysis of Sparse Approximate Inverse Preconditioners for Boundary Integral Equations
Preconditioning techniques for dense linear systems arising from singular boundary integral equations are described and analyzed. A particular class of approximate inverse based preconditioners related to the mesh neighbor methods is known to be efficient. This paper shows that it is an operator splitting preconditioner and clusters eigenvalues for the normal equation matrix thus ensuring a fast convergence of the conjugate gradient normal method. Clustering of the eigenvalues of the preconditioned matrix and fast convergence of the generalized minimal residual method are also observed. For the type of problems considered, we demonstrate a crucial connection between two essential features of eigenvalue clustering for a sparse preconditioner---approximate inversion for a small cluster radius and operator splitting for a small cluster size. Experimental results from several boundary integral equations are presented.
25215706
On Two Variants of an Algebraic Wavelet Preconditioner
A recursive method of constructing preconditioning matrices for the nonsymmetric stiffness matrix in a wavelet basis is proposed for solving a class of integral and differential equations. It is based on a level-by-level application of the wavelet scales decoupling the different wavelet levels in a matrix form just as in the well-known nonstandard form. The result is a powerful iterative method with built-in preconditioning leading to two specific algebraic multilevel iteration algorithms: one with an exact Schur preconditioning and the other with an approximate Schur preconditioning. Numerical examples are presented to illustrate the efficiency of the new algorithms.
17327326
UBM-based incremental speaker adaptation
This paper addresses a novel algorithm of incremental speaker adaptation (ISA) based on universal background model (UBM) for saving storage and real-time processing. This algorithm can be seen as an extension of traditional speaker adaptation. It consists of two steps, adaptation and combination. It not only considers the speaker's characteristics in limited training data, but also prohibits over-fitting of the updated model. The incremental adaptation algorithm needs little storage and meets the requirement of real-time processing. In order to evaluate the efficiency and effectivity of the proposed approach, a real-time speaker segmentation system for broadcasting news is built. Experiment results demonstrate that our approach yields real time operation and achieves satisfactory performance.