Using pseudo amino acid composition and binary-tree support vector machines to predict protein structural classes

Compared with the conventional amino acid composition (AA), the pseudo amino acid composition (PseAA) as originally introduced by Chou can incorporate much more information of a protein sequence; this remarkably enhances the power to use a discrete model for predicting various attributes of a protein. In this study, based on the concept of Chou's PseAA, a 46-D (dimensional) PseAA was formulated to represent the sample of a protein and a new approach based on binary-tree support vector machines (BTSVMs) was proposed to predict the protein structural class. BTSVMs algorithm has the capability in solving the problem of unclassifiable data points in multi-class SVMs. The results by both the 10-fold cross-validation and jackknife tests demonstrate that the predictive performance using the new PseAA (46-D) is better than that of AA (20-D), which is widely used in many algorithms for protein structural class prediction. The results obtained by the new approach are quite encouraging, indicating that it can at least play a complimentary role to many of the existing methods and is a useful tool for predicting many other protein attributes as well.     

Using the concept of Chou's pseudo amino acid composition to predict apoptosis proteins subcellular location: an approach by approximate entropy

The function of protein is closely correlated with it subcellular location. Prediction of subcellular location of apoptosis proteins is an important research area in post-genetic era because the knowledge of apoptosis proteins is useful to understand the mechanism of programmed cell death. Compared with the conventional amino acid composition (AAC), the Pseudo Amino Acid composition (PseAA) as originally introduced by Chou can incorporate much more information of a protein sequence so as to remarkably enhance the power of using a discrete model to predict various attributes of a protein. In this study, a novel approach is presented to predict apoptosis protein solely from sequence based on the concept of Chou's PseAA composition. The concept of approximate entropy (ApEn), which is a parameter denoting complexity of time series, is used to construct PseAA composition as additional features. Fuzzy K-nearest neighbor (FKNN) classifier is selected as prediction engine. Particle swarm optimization (PSO) algorithm is adopted for optimizing the weight factors which are important in PseAA composition. Two datasets are used to validate the performance of the proposed approach, which incorporate six subcellular location and four subcellular locations, respectively. The results obtained by jackknife test are quite encouraging. It indicates that the ApEn of protein sequence could represent effectively the information of apoptosis proteins subcellular locations. It can at least play a complimentary role to many of the existing methods, and might become potentially useful tool for protein function prediction. The software in Matlab is available freely by contacting the corresponding author.     

PseAAC: a flexible web server for generating various kinds of protein pseudo amino acid composition

The pseudo amino acid (PseAA) composition can represent a protein sequence in a discrete model without completely losing its sequence-order information, and hence has been widely applied for improving the prediction quality for various protein attributes. However, dealing with different problems may need different kinds of PseAA composition. Here, we present a web-server called PseAAC at http://chou.med.harvard.edu/bioinf/PseAA/, by which users can generate various kinds of PseAA composition to best fit their need.     

基于近似熵的伪氨基酸组成预测蛋白质亚核定位

了解真核细胞中细胞核内蛋白质的定位情况对于新发现蛋白质的功能注释具有重要意义.随着蛋白质数据库中蛋白质序列数量的急速增加,采用计算方法来预测蛋白质亚核定位已经成为蛋白质科学领域研究的热点.根据Chou提出的伪氨基酸组成离散模型,提出了一种新的蛋白质亚核定位预测方法.计算蛋白质序列的近似熵作为附加特征构建伪氨基酸组成,表示蛋白质序列特征,AdaBoost分类算法作为预测工具.与已报道的亚核定位预测方法的性能相比,这种方法具有更高的准确率.     

Prediction of protein structure classes with pseudo amino acid composition and fuzzy support vector machine network

It is a critical challenge to develop automated methods for fast and accurately determining the structures of proteins because of the increasingly widening gap between the number of sequence-known proteins and that of structure-known proteins in the post-genomic age. The knowledge of protein structural class can provide useful information towards the determination of protein structure. Thus, it is highly desirable to develop computational methods for identifying the structural classes of newly found proteins based on their primary sequence. In this study, according to the concept of Chou's pseudo amino acid composition (PseAA), eight PseAA vectors are used to represent protein samples. Each of the PseAA vectors is a 40-D (dimensional) vector, which is constructed by the conventional amino acid composition (AA) and a series of sequence-order correlation factors as original introduced by Chou. The difference among the eight PseAA representations is that different physicochemical properties are used to incorporate the sequence-order effects for the protein samples. Based on such a framework, a dual-layer fuzzy support vector machine (FSVM) network is proposed to predict protein structural classes. In the first layer of the FSVM network, eight FSVM classifiers trained by different PseAA vectors are established. The 2nd layer FSVM classifier is applied to reclassify the outputs of the first layer. The results thus obtained are quite promising, indicating that the new method may become a useful tool for predicting not only the structural classification of proteins but also their other attributes.     

Using pseudo amino acid composition to predict protein subnuclear location with improved hybrid approach

Summary. The subnuclear localization of nuclear protein is very important for in-depth understanding of the construction and function of the nucleus. Based on the amino acid and pseudo amino acid composition (PseAA) as originally introduced by K. C. Chou can incorporate much more information of a protein sequence than the classical amino acid composition so as to significantly enhance the power of using a discrete model to predict various attributes of a protein, an algorithm of increment of diversity combined with the improved quadratic discriminant analysis is proposed to predict the protein subnuclear location. The overall predictive success rates and correlation coefficient are 75.4% and 0.629 for 504 single localization proteins in jackknife test, and 80.4% for an independent set of 92 multi-localization proteins, respectively. For 406 single localization nuclear proteins with ≤25% sequence identity, the results of jackknife test show that the overall accuracy of prediction is 77.1%. Authors’ address: Qian-Zhong Li, Laboratory of Theoretical Biophysics, Department of Physics, College of Sciences and Technology, Inner Mongolia University, Hohhot 010021, China     

Predicting protein subcellular location using Chou's pseudo amino acid composition and improved hybrid approach

The location of a protein in a cell is closely correlated with its biological function. Based on the concept that the protein subcellular location is mainly determined by its amino acid and pseudo amino acid composition (PseAA), a new algorithm of increment of diversity combined with support vector machine is proposed to predict the protein subcellular location. The subcellular locations of plant and non-plant proteins are investigated by our method. The overall prediction accuracies in jackknife test are 88.3% for the eukaryotic plant proteins and 92.4% for the eukaryotic non-plant proteins, respectively. In order to estimate the effect of the sequence identity on predictive result, the proteins with sequence identity 相似文献   

Using Chou’s pseudo amino acid composition based on approximate entropy and an ensemble of AdaBoost classifiers to predict protein subnuclear location

The knowledge of subnuclear localization in eukaryotic cells is essential for understanding the life function of nucleus. Developing prediction methods and tools for proteins subnuclear localization become important research fields in protein science for special characteristics in cell nuclear. In this study, a novel approach has been proposed to predict protein subnuclear localization. Sample of protein is represented by Pseudo Amino Acid (PseAA) composition based on approximate entropy (ApEn) concept, which reflects the complexity of time series. A novel ensemble classifier is designed incorporating three AdaBoost classifiers. The base classifier algorithms in three AdaBoost are decision stumps, fuzzy K nearest neighbors classifier, and radial basis-support vector machines, respectively. Different PseAA compositions are used as input data of different AdaBoost classifier in ensemble. Genetic algorithm is used to optimize the dimension and weight factor of PseAA composition. Two datasets often used in published works are used to validate the performance of the proposed approach. The obtained results of Jackknife cross-validation test are higher and more balance than them of other methods on same datasets. The promising results indicate that the proposed approach is effective and practical. It might become a useful tool in protein subnuclear localization. The software in Matlab and supplementary materials are available freely by contacting the corresponding author.     

Prediction of protein–protein interactions based on PseAA composition and hybrid feature selection

Based on pseudo amino acid (PseAA) composition and a novel hybrid feature selection frame, this paper presents a computational system to predict the PPIs (protein–protein interactions) using 8796 protein pairs. These pairs are coded by PseAA composition, resulting in 114 features. A hybrid feature selection system, mRMR–KNNs–wrapper, is applied to obtain an optimized feature set by excluding poor-performed and/or redundant features, resulting in 103 remaining features. Using the optimized 103-feature subset, a prediction model is trained and tested in the k-nearest neighbors (KNNs) learning system. This prediction model achieves an overall accurate prediction rate of 76.18%, evaluated by 10-fold cross-validation test, which is 1.46% higher than using the initial 114 features and is 6.51% higher than the 20 features, coded by amino acid compositions. The PPIs predictor, developed for this research, is available for public use at http://chemdata.shu.edu.cn/ppi.     

Prediction of protein subcellular localization by support vector machines using multi-scale energy and pseudo amino acid composition

As more and more genomes have been discovered in recent years, there is an urgent need to develop a reliable method to predict the subcellular localization for the explosion of newly found proteins. However, many well-known prediction methods based on amino acid composition have problems utilizing the sequence-order information. Here, based on the concept of Chou's pseudo amino acid composition (PseAA), a new feature extraction method, the multi-scale energy (MSE) approach, is introduced to incorporate the sequence-order information. First, a protein sequence was mapped to a digital signal using the amino acid index. Then, by wavelet transform, the mapped signal was broken down into several scales in which the energy factors were calculated and further formed into an MSE feature vector. Following this, combining this MSE feature vector with amino acid composition (AA), we constructed a series of MSEPseAA feature vectors to represent the protein subcellular localization sequences. Finally, according to a new kind of normalization approach, the MSEPseAA feature vectors were normalized to form the improved MSEPseAA vectors, named as IEPseAA. Using the technique of IEPseAA, C-support vector machine (C-SVM) and three multi-class SVMs strategies, quite promising results were obtained, indicating that MSE is quite effective in reflecting the sequence-order effects and might become a useful tool for predicting the other attributes of proteins as well.     

Using pseudo amino acid composition to predict protein subcellular location: approached with amino acid composition distribution

In the Post Genome Age, there is an urgent need to develop the reliable and effective computational methods to predict the subcellular localization for the explosion of newly found proteins. Here, a novel method of pseudo amino acid (PseAA) composition, the so-called “amino acid composition distribution” (AACD), is introduced. First, a protein sequence is divided equally into multiple segments. Then, amino acid composition of each segment is calculated in series. After that, each protein sequence can be represented by a feature vector. Finally, the feature vectors of all sequences thus obtained are further input into the multi-class support vector machines to predict the subcellular localization. The results show that AACD is quite effective in representing protein sequences for the purpose of predicting protein subcellular localization.     

Prediction of membrane proteins using split amino acid and ensemble classification

Knowledge of the types of membrane protein provides useful clues in deducing the functions of uncharacterized membrane proteins. An automatic method for efficiently identifying uncharacterized proteins is thus highly desirable. In this work, we have developed a novel method for predicting membrane protein types by exploiting the discrimination capability of the difference in amino acid composition at the N and C terminus through split amino acid composition (SAAC). We also show that the ensemble classification can better exploit this discriminating capability of SAAC. In this study, membrane protein types are classified using three feature extraction and several classification strategies. An ensemble classifier Mem-EnsSAAC is then developed using the best feature extraction strategy. Pseudo amino acid (PseAA) composition, discrete wavelet analysis (DWT), SAAC, and a hybrid model are employed for feature extraction. The nearest neighbor, probabilistic neural network, support vector machine, random forest, and Adaboost are used as individual classifiers. The predicted results of the individual learners are combined using genetic algorithm to form an ensemble classifier, Mem-EnsSAAC yielding an accuracy of 92.4 and 92.2% for the Jackknife and independent dataset test, respectively. Performance measures such as MCC, sensitivity, specificity, F-measure, and Q-statistics show that SAAC-based prediction yields significantly higher performance compared to PseAA- and DWT-based systems, and is also the best reported so far. The proposed Mem-EnsSAAC is able to predict the membrane protein types with high accuracy and consequently, can be very helpful in drug discovery. It can be accessed at http://111.68.99.218/membrane.     

Prediction of protein cellular attributes using pseudo-amino acid composition

The cellular attributes of a protein, such as which compartment of a cell it belongs to and how it is associated with the lipid bilayer of an organelle, are closely correlated with its biological functions. The success of human genome project and the rapid increase in the number of protein sequences entering into data bank have stimulated a challenging frontier: How to develop a fast and accurate method to predict the cellular attributes of a protein based on its amino acid sequence? The existing algorithms for predicting these attributes were all based on the amino acid composition in which no sequence order effect was taken into account. To improve the prediction quality, it is necessary to incorporate such an effect. However, the number of possible patterns for protein sequences is extremely large, which has posed a formidable difficulty for realizing this goal. To deal with such a difficulty, the pseudo‐amino acid composition is introduced. It is a combination of a set of discrete sequence correlation factors and the 20 components of the conventional amino acid composition. A remarkable improvement in prediction quality has been observed by using the pseudo‐amino acid composition. The success rates of prediction thus obtained are so far the highest for the same classification schemes and same data sets. It has not escaped from our notice that the concept of pseudo‐amino acid composition as well as its mathematical framework and biochemical implication may also have a notable impact on improving the prediction quality of other protein features. Proteins 2001;43:246–255. © 2001 Wiley‐Liss, Inc.     

Predicting protein structural class with pseudo-amino acid composition and support vector machine fusion network

Because a priori knowledge of a protein structural class can provide useful information about its overall structure, the determination of protein structural class is a quite meaningful topic in protein science. However, with the rapid increase in newly found protein sequences entering into databanks, it is both time-consuming and expensive to do so based solely on experimental techniques. Therefore, it is vitally important to develop a computational method for predicting the protein structural class quickly and accurately. To deal with the challenge, this article presents a dual-layer support vector machine (SVM) fusion network that is featured by using a different pseudo-amino acid composition (PseAA). The PseAA here contains much information that is related to the sequence order of a protein and the distribution of the hydrophobic amino acids along its chain. As a showcase, the rigorous jackknife cross-validation test was performed on the two benchmark data sets constructed by Zhou. A significant enhancement in success rates was observed, indicating that the current approach may serve as a powerful complementary tool to other existing methods in this area.     

Prediction of apoptosis protein subcellular location using improved hybrid approach and pseudo-amino acid composition

Apoptosis proteins are very important for understanding the mechanism of programmed cell death. The apoptosis protein localization can provide valuable information about its molecular function. The prediction of localization of an apoptosis protein is a challenging task. In our previous work we proposed an increment of diversity (ID) method using protein sequence information for this prediction task. In this work, based on the concept of Chou's pseudo-amino acid composition [Chou, K.C., 2001. Prediction of protein cellular attributes using pseudo-amino acid composition. Proteins: Struct. Funct. Genet. (Erratum: Chou, K.C., 2001, vol. 44, 60) 43, 246-255, Chou, K.C., 2005. Using amphiphilic pseudo-amino acid composition to predict enzyme subfamily classes. Bioinformatics 21, 10-19], a different pseudo-amino acid composition by using the hydropathy distribution information is introduced. A novel ID_SVM algorithm combined ID with support vector machine (SVM) is proposed. This method is applied to three data sets (317 apoptosis proteins, 225 apoptosis proteins and 98 apoptosis proteins). The higher predictive success rates than the previous algorithms are obtained by the jackknife tests.     

Using pseudo-amino acid composition and support vector machine to predict protein structural class

As a result of genome and other sequencing projects, the gap between the number of known protein sequences and the number of known protein structural classes is widening rapidly. In order to narrow this gap, it is vitally important to develop a computational prediction method for fast and accurately determining the protein structural class. In this paper, a novel predictor is developed for predicting protein structural class. It is featured by employing a support vector machine learning system and using a different pseudo-amino acid composition (PseAA), which was introduced to, to some extent, take into account the sequence-order effects to represent protein samples. As a demonstration, the jackknife cross-validation test was performed on a working dataset that contains 204 non-homologous proteins. The predicted results are very encouraging, indicating that the current predictor featured with the PseAA may play an important complementary role to the elegant covariant discriminant predictor and other existing algorithms.     

Predicting protein subcellular location using digital signal processing

The biological functions of a protein are closely related to its attributes in a cell. With the rapid accumulation of newly found protein sequence data in databanks, it is highly desirable to develop an automated method for predicting the subcellular location of proteins. The establishment of such a predictor will expedite the functional determination of newly found proteins and the process of prioritizing genes and proteins identified by genomic efforts as potential molecular targets for drug design. The traditional algorithms for predicting these attributes were based solely on amino acid composition in which no sequence order effect was taken into account. To improve the prediction quality, it is necessary to incorporate such an effect. However, the number of possible patterns in protein sequences is extremely large, posing a formidable difficulty for realizing this goal. To deal with such difficulty, a well-developed tool in digital signal processing named digital Fourier transform (DFT) [1] was introduced. After being translated to a digital signal according to the hydrophobicity of each amino acid, a protein was analyzed by DFT within the frequency domain. A set of frequency spectrum parameters, thus obtained, were regarded as the factors to represent the sequence order effect. A significant improvement in prediction quality was observed by incorporating the frequency spectrum parameters with the conventional amino acid composition. One of the crucial merits of this approach is that many existing tools in mathematics and engineering can be easily applied in the predicting process. It is anticipated that digital signal processing may serve as a useful vehicle for many other protein science areas.     

Prediction of thermostability from amino acid attributes by combination of clustering with attribute weighting: a new vista in engineering enzymes

The engineering of thermostable enzymes is receiving increased attention. The paper, detergent, and biofuel industries, in particular, seek to use environmentally friendly enzymes instead of toxic chlorine chemicals. Enzymes typically function at temperatures below 60°C and denature if exposed to higher temperatures. In contrast, a small portion of enzymes can withstand higher temperatures as a result of various structural adaptations. Understanding the protein attributes that are involved in this adaptation is the first step toward engineering thermostable enzymes. We employed various supervised and unsupervised machine learning algorithms as well as attribute weighting approaches to find amino acid composition attributes that contribute to enzyme thermostability. Specifically, we compared two groups of enzymes: mesostable and thermostable enzymes. Furthermore, a combination of attribute weighting with supervised and unsupervised clustering algorithms was used for prediction and modelling of protein thermostability from amino acid composition properties. Mining a large number of protein sequences (2090) through a variety of machine learning algorithms, which were based on the analysis of more than 800 amino acid attributes, increased the accuracy of this study. Moreover, these models were successful in predicting thermostability from the primary structure of proteins. The results showed that expectation maximization clustering in combination with uncertainly and correlation attribute weighting algorithms can effectively (100%) classify thermostable and mesostable proteins. Seventy per cent of the weighting methods selected Gln content and frequency of hydrophilic residues as the most important protein attributes. On the dipeptide level, the frequency of Asn-Glu was the key factor in distinguishing mesostable from thermostable enzymes. This study demonstrates the feasibility of predicting thermostability irrespective of sequence similarity and will serve as a basis for engineering thermostable enzymes in the laboratory.