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.     

基于氨基酸和二肽组成的蛋白质四级结构分类研究

基于最近邻居算法,从蛋白质一级序列出发,利用蛋白质序列氨基酸组成、二肤组成以及混合组成方法对蛋白质单聚体、二聚体、三聚体、四聚体、五聚体、六聚体和八聚体进行分类研究。结果表明:采用二肽组成编码方法的预洲效果最好,Jackknife检验和独立测试集检验的总体预测精度分别达到90.83%和95.48%,比相同数据集上基于伪氨基酸组成和组分耦合预测的方法提高了12和15个百分点;特别是对于五聚体蛋白,预测精度分别提高了90和50个百分点;说明二肽组成对于蛋白质四级结构分类研究是一种非常有效的特征提取方法。     

Predicting protein structural classes with pseudo amino acid composition: an approach using geometric moments of cellular automaton image

A novel approach was developed for predicting the structural classes of proteins based on their sequences. It was assumed that proteins belonging to the same structural class must bear some sort of similar texture on the images generated by the cellular automaton evolving rule [Wolfram, S., 1984. Cellular automation as models of complexity. Nature 311, 419-424]. Based on this, two geometric invariant moment factors derived from the image functions were used as the pseudo amino acid components [Chou, K.C., 2001. Prediction of protein cellular attributes using pseudo amino acid composition. Proteins: Struct., Funct., Genet. (Erratum: ibid., 2001, vol. 44, 60) 43, 246-255] to formulate the protein samples for statistical prediction. The success rates thus obtained on a previously constructed benchmark dataset are quite promising, implying that the cellular automaton image can help to reveal some inherent and subtle features deeply hidden in a pile of long and complicated amino acid sequences.     

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   

Predicting enzyme family classes by hybridizing gene product composition and pseudo-amino acid composition

A new method has been developed to predict the enzymatic attribute of proteins by hybridizing the gene product composition and pseudo amino acid composition. As a demonstration, a working dataset was generated with a cutoff of 60% sequence identity to avoid redundancy and bias in statistical prediction. The dataset thus constructed contains 39989 protein sequences, of which 27469 are non-enzymes and 12520 enzymes that were further classified into 6 enzyme family classes according to their 6 main EC (Enzyme Commission) numbers (2314 are oxidoreductases, 3653 transferases, 3246 hydrolases, 1307 lyases, 676 isomerases, and 1324 ligases). The overall success rate by the jackknife test for the identification between enzyme and non-enzyme was 94%, and that for the identification among the 6 enzyme family classes was 98%. It is anticipated that, with the rapid increase of protein sequences entering into databanks, the current method will become a useful automated tool in identifying the enzymatic attribute of a newly found protein sequence.     

Predicting membrane protein types with bragging learner

The membrane protein type is an important feature in characterizing the overall topological folding type of a protein or its domains therein. Many investigators have put their efforts to the prediction of membrane protein type. Here, we propose a new approach, the bootstrap aggregating method or bragging learner, to address this problem based on the protein amino acid composition. As a demonstration, the benchmark dataset constructed by K.C. Chou and D.W. Elrod was used to test the new method. The overall success rate thus obtained by jackknife cross-validation was over 84%, indicating that the bragging learner as presented in this paper holds a quite high potential in predicting the attributes of proteins, or at least can play a complementary role to many existing algorithms in this area. It is anticipated that the prediction quality can be further enhanced if the pseudo amino acid composition can be effectively incorporated into the current predictor. An online membrane protein type prediction web server developed in our lab is available at http://chemdata.shu.edu.cn/protein/protein.jsp.     

随机森林方法预测膜蛋白类型

膜蛋白的类型与其功能是密切相关的,因此膜蛋白类型的预测是研究其功能的重要手段,从蛋白质的氨基酸序列出发对膜蛋白的类型进行预测有重要意义。文章基于蛋白质的氨基酸序列,将组合离散增量和伪氨基酸组分信息共同作为预测参数,采用随机森林分类器,对8类膜蛋白进行了预测。在Jackknife检验下的预测精度为86.3%,独立检验的预测精度为93.8%,取得了好于前人的预测结果。     

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 subcellular multi-localization based on the general form of Chou's pseudo amino acid composition

Many proteins bear multi-locational characteristics, and this phenomenon is closely related to biological function. However, most of the existing methods can only deal with single-location proteins. Therefore, an automatic and reliable ensemble classifier for protein subcellular multi-localization is needed. We propose a new ensemble classifier combining the KNN (K-nearest neighbour) and SVM (support vector machine) algorithms to predict the subcellular localization of eukaryotic, Gram-negative bacterial and viral proteins based on the general form of Chou's pseudo amino acid composition, i.e., GO (gene ontology) annotations, dipeptide composition and AmPseAAC (Amphiphilic pseudo amino acid composition). This ensemble classifier was developed by fusing many basic individual classifiers through a voting system. The overall prediction accuracies obtained by the KNN-SVM ensemble classifier are 95.22, 93.47 and 80.72% for the eukaryotic, Gram-negative bacterial and viral proteins, respectively. Our prediction accuracies are significantly higher than those by previous methods and reveal that our strategy better predicts subcellular locations of multi-location proteins.     

SLLE for predicting membrane protein types

Introduction of the concept of pseudo amino acid composition (PROTEINS: Structure, Function, and Genetics 43 (2001) 246; Erratum: ibid. 44 (2001) 60) has made it possible to incorporate a considerable amount of sequence-order effects by representing a protein sample in terms of a set of discrete numbers, and hence can significantly enhance the prediction quality of membrane protein type. As a continuous effort along such a line, the Supervised Locally Linear Embedding (SLLE) technique for nonlinear dimensionality reduction is introduced (Science 22 (2000) 2323). The advantage of using SLLE is that it can reduce the operational space by extracting the essential features from the high-dimensional pseudo amino acid composition space, and that the cluster-tolerant capacity can be increased accordingly. As a consequence by combining these two approaches, high success rates have been observed during the tests of self-consistency, jackknife and independent data set, respectively, by using the simplest nearest neighbour classifier. The current approach represents a new strategy to deal with the problems of protein attribute prediction, and hence may become a useful vehicle in the area of bioinformatics and proteomics.     

Fold homology detection using sequence fragment composition profiles of proteins

The effectiveness of sequence alignment in detecting structural homology among protein sequences decreases markedly when pairwise sequence identity is low (the so‐called “twilight zone” problem of sequence alignment). Alternative sequence comparison strategies able to detect structural kinship among highly divergent sequences are necessary to address this need. Among them are alignment‐free methods, which use global sequence properties (such as amino acid composition) to identify structural homology in a rapid and straightforward way. We explore the viability of using tetramer sequence fragment composition profiles in finding structural relationships that lie undetected by traditional alignment. We establish a strategy to recast any given protein sequence into a tetramer sequence fragment composition profile, using a series of amino acid clustering steps that have been optimized for mutual information. Our method has the effect of compressing the set of 160,000 unique tetramers (if using the 20‐letter amino acid alphabet) into a more tractable number of reduced tetramers (～15–30), so that a meaningful tetramer composition profile can be constructed. We test remote homology detection at the topology and fold superfamily levels using a comprehensive set of fold homologs, culled from the CATH database that share low pairwise sequence similarity. Using the receiver‐operating characteristic measure, we demonstrate potentially significant improvement in using information‐optimized reduced tetramer composition, over methods relying only on the raw amino acid composition or on traditional sequence alignment, in homology detection at or below the “twilight zone”. Proteins 2010. © 2010 Wiley‐Liss, Inc.     

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     

An overview on predicting the subcellular location of a protein

The present paper overviews the issue on predicting the subcellular location of a protein. Five measures of extracting information from the global sequence based on the Bayes discriminant algorithm are reviewed. 1) The auto-correlation functions of amino acid indices along the sequence; 2) The quasi-sequence-order approach; 3) the pseudo-amino acid composition; 4) the unified attribute vector in Hilbert space, 5) Zp parameters extracted from the Zp curve. The actual performance of the predictive accuracy is closely related to the degree of similarity between the training and testing sets or to the average degree of pairwise similarity in dataset in a cross-validated study. Many scholars considered that the current higher predictive accuracy still cannot ensure that some available algorithms are effective in practice prediction for the higher pairwise sequence identity of the datasets, but some of them declared that construction of the dataset used for developing software should base on the reality determined by the Mother Nature that some subcellular locations really contain only a minor number of proteins of which some even have a high percentage of sequence similarity. Owing to the complexity of the problem itself, some very sophisticated and special programs are needed for both constructing dataset and improving the prediction. Anyhow finding the target information in mature protein sequence and properly cooperating it with sorting signals in prediction may further improve the overall predictive accuracy and make the prediction into practice.     

Prediction of protein secondary structure content using amino acid composition and evolutionary information

Knowing protein structure and inferring its function from the structure are one of the main issues of computational structural biology, and often the first step is studying protein secondary structure. There have been many attempts to predict protein secondary structure contents. Previous attempts assumed that the content of protein secondary structure can be predicted successfully using the information on the amino acid composition of a protein. Recent methods achieved remarkable prediction accuracy by using the expanded composition information. The overall average error of the most successful method is 3.4%. Here, we demonstrate that even if we only use the simple amino acid composition information alone, it is possible to improve the prediction accuracy significantly if the evolutionary information is included. The idea is motivated by the observation that evolutionarily related proteins share the similar structure. After calculating the homolog-averaged amino acid composition of a protein, which can be easily obtained from the multiple sequence alignment by running PSI-BLAST, those 20 numbers are learned by a multiple linear regression, an artificial neural network and a support vector regression. The overall average error of method by a support vector regression is 3.3%. It is remarkable that we obtain the comparable accuracy without utilizing the expanded composition information such as pair-coupled amino acid composition. This work again demonstrates that the amino acid composition is a fundamental characteristic of a protein. It is anticipated that our novel idea can be applied to many areas of protein bioinformatics where the amino acid composition information is utilized, such as subcellular localization prediction, enzyme subclass prediction, domain boundary prediction, signal sequence prediction, and prediction of unfolded segment in a protein sequence, to name a few.     

Using complexity measure factor to predict protein subcellular location

Summary. Recent advances in large-scale genome sequencing have led to the rapid accumulation of amino acid sequences of proteins whose functions are unknown. Because the functions of these proteins are closely correlated with their subcellular localizations, it is vitally important to develop an automated method as a high-throughput tool to timely identify their subcellular location. Based on the concept of the pseudo amino acid composition by which a considerable amount of sequence-order effects can be incorporated into a set of discrete numbers (Chou, K. C., Proteins: Structure, Function, and Genetics, 2001, 43: 246–255), the complexity measure approach is introduced. The advantage by incorporating the complexity measure factor as one of the pseudo amino acid components for a protein is that it can more effectively reflect its overall sequence-order feature than the conventional correlation factors. With such a formulation frame to represent the samples of protein sequences, the covariant-discriminant predictor (Chou, K. C. and Elrod, D. W., Protein Engineering, 1999, 12: 107–118) was adopted to conduct prediction. High success rates were obtained by both the jackknife cross-validation test and independent dataset test, suggesting that introduction of the concept of the complexity measure into prediction of protein subcellular location is quite promising, and might also hold a great potential as a useful vehicle for the other areas of molecular biology.     

Predicting subcellular localization of mycobacterial proteins by using Chou's pseudo amino acid composition

The successful prediction of protein subcellular localization directly from protein primary sequence is useful to protein function prediction and drug discovery. In this paper, by using the concept of pseudo amino acid composition (PseAAC), the mycobacterial proteins are studied and predicted by support vector machine (SVM) and increment of diversity combined with modified Mahalanobis Discriminant (IDQD). The results of jackknife cross-validation for 450 non-redundant proteins show that the overall predicted successful rates of SVM and IDQD are 82.2% and 79.1%, respectively. Compared with other existing methods, SVM combined with PseAAC display higher accuracies.     

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.     

利用伪氨基酸组分和支持向量机预测抗冻蛋白

抗冻蛋白是一类具有提高生物抗冻能力的蛋白质。抗冻蛋白能够特异性的与冰晶相结合,进而阻止体液内冰核的形成与生长。因此,对抗冻蛋白的生物信息学研究对生物工程发展。提高作物抗冻性有重要的推动作用。本文采用由400条抗冻蛋白序列和400条非抗冻蛋白序列构成数据集,以伪氨基酸组分为特征,利用支持向量机分类算法预测抗冻蛋白,对训练集预测精度达到91．3％,对测试集预测精度达到78．8％。该结果证明伪氨基酸组分能够很好的反映抗冻蛋白特性,并能够用于预测抗冻蛋白。