General PseAAC Research Articles

ILipo-PseAAC: Identification of Lipoylation Sites Using Statistical Moments and General PseAAC

Lysine Lipoylation is a protective and conserved Post Translational Modification (PTM) in proteomics research like prokaryotes and eukaryotes. It is connected with many biological processes and closely linked with many metabolic diseases. To develop a perfect and accurate classification model for identifying lipoylation sites at the protein level, the computational methods and several other factors play a key role in this purpose. Usually, most of the techniques and different traditional experimental models have a very high cost. They are time-consuming; so, it is required to construct a predictor model to extract lysine lipoylation sites. This study proposes a model that could predict lysine lipoylation sites with the help of a classification method known as Artificial Neural Network (ANN). The ANN algorithm deals with the noise problem and imbalance classification in lipoylation sites dataset samples. As the result shows in ten-fold cross-validation, a brilliant performance is achieved through the predictor model with an accuracy of 99.88%, and also achieved 0.9976 as the highest value of MCC. So, the predictor model is a very useful and helpful tool for lipoylation sites prediction. Some of the residues around lysine lipoylation sites play a vital part in prediction, as demonstrated during feature analysis. The wonderful results reported through the evaluation and prediction of this model can provide an informative and relative explanation for lipoylation and its molecular mechanisms.

IDRP-PseAAC: Identification of DNA Replication Proteins Using General PseAAC and Position Dependent Features.

DNA replication is one of the specific processes to be considered in all the living organisms, specifically eukaryotes. The prevalence of DNA replication is significant for an evolutionary transition at the beginning of life. DNA replication proteins are those proteins which support the process of replication and are also reported to be important in drug design and discovery. This information depicts that DNA replication proteins have a very important role in human bodies, however, to study their mechanism, their identification is necessary. Thus, it is a very important task but, in any case, an experimental identification is time-consuming, highly-costly and laborious. To cope with this issue, a computational methodology is required for prediction of these proteins, however, no prior method exists. This study comprehends the construction of novel prediction model to serve the proposed purpose. The prediction model is developed based on the artificial neural network by integrating the position relative features and sequence statistical moments in PseAAC for training neural networks. Highest overall accuracy has been achieved through tenfold cross-validation and Jackknife testing that was computed to be 96.22% and 98.56%, respectively. Our astonishing experimental results demonstrated that the proposed predictor surpass the existing models that can be served as a time and cost-effective stratagem for designing novel drugs to strike the contemporary bacterial infection.

Identification of Lysine Carboxylation Sites in Proteins by Integrating Statistical Moments and Position Relative Features via General PseAAC

Background:Carboxylation is one of the most biologically important post-translational modifications and occurs on lysine, arginine, and glutamine residues of a protein. Among all these three, the covalent attachment of the carboxyl group with the lysine side chain is the most frequent and biologically important type of carboxylation. For studying such biological functions, it is essential to correctly determine the lysine sites sensitive to carboxylation.Objective:Herein, we present a computational model for the prediction of the carboxylysine site which is based on machine learning.Methods:Various position and composition relative features have been incorporated into the Pse- AAC for construction of feature vectors and a neural network is employed as a classifier. The model is validated by jackknife, cross-validation, self-consistency, and independent testing.Results:The results of the self-consistency test elaborated that model has 99.76% Acc, 99.76% Sp, 99.76% Sp, and 0.99 MCC. Using the jackknife method, prediction model validation gave 97.07% Acc, while for 10-fold cross-validation, prediction model validation gave 95.16% Acc.Conclusion:The results of independent dataset testing were 94.3% which illustrated that the proposed model has better performance as compared to the existing model PreLysCar; however, the accuracy can be improved further, in the future, due to the increasing number of carboxylysine sites in proteins.

IProtease-PseAAC(2L): A two-layer predictor for identifying proteases and their types using Chou's 5-step-rule and general PseAAC

Proteases are a type of enzymes, which perform the process of proteolysis. Proteolysis normally refers to protein and peptide degradation which is crucial for the survival, growth and wellbeing of a cell. Moreover, proteases have a strong association with therapeutics and drug development. The proteases are classified into five different types according to their nature and physiochemical characteristics. Mostly the methods used to differentiate protease from other proteins and identify their class requires a clinical test which is usually time-consuming and operator dependent. Herein, we report a classifier named iProtease-PseAAC (2L) for identifying proteases and their classes. The predictor is developed employing the flow of 5-step rule, initiating from the collection of benchmark dataset and terminating at the development of predictor. Rigorous verification and validation tests are performed and metrics are collected to calculate the authenticity of the trained model. The self-consistency validation gives the 98.32% accuracy, for cross-validation the accuracy is 90.71% and jackknife gives 96.07% accuracy. The average accuracy for level-2 i.e. protease classification is 95.77%. Based on the above-mentioned results, it is concluded that iProtease-PseAAC (2L) has the great ability to identify the proteases and their classes using a given protein sequence.

PLoc_bal-mEuk: Predict Subcellular Localization of Eukaryotic Proteins by General PseAAC and Quasi-balancing Training Dataset.

Information of protein subcellular localization is crucially important for both basic research and drug development. With the explosive growth of protein sequences discovered in the post-genomic age, it is highly demanded to develop powerful bioinformatics tools for timely and effectively identifying their subcellular localization purely based on the sequence information alone. Recently, a predictor called "pLoc-mEuk" was developed for identifying the subcellular localization of eukaryotic proteins. Its performance is overwhelmingly better than that of the other predictors for the same purpose, particularly in dealing with multi-label systems where many proteins, called "multiplex proteins", may simultaneously occur in two or more subcellular locations. Although it is indeed a very powerful predictor, more efforts are definitely needed to further improve it. This is because pLoc-mEuk was trained by an extremely skewed dataset where some subset was about 200 times the size of the other subsets. Accordingly, it cannot avoid the biased consequence caused by such an uneven training dataset. To alleviate such bias, we have developed a new predictor called pLoc_bal-mEuk by quasi-balancing the training dataset. Cross-validation tests on exactly the same experimentconfirmed dataset have indicated that the proposed new predictor is remarkably superior to pLocmEuk, the existing state-of-the-art predictor in identifying the subcellular localization of eukaryotic proteins. It has not escaped our notice that the quasi-balancing treatment can also be used to deal with many other biological systems. To maximize the convenience for most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc_bal-mEuk/. It is anticipated that the pLoc_bal-Euk predictor holds very high potential to become a useful high throughput tool in identifying the subcellular localization of eukaryotic proteins, particularly for finding multi-target drugs that is currently a very hot trend trend in drug development.

IMethylK_pseAAC: Improving Accuracy of Lysine Methylation Sites Identification by Incorporating Statistical Moments and Position Relative Features into General PseAAC via Chou's 5-steps Rule.

Background: Methylation is one of the most important post-translational modifications in the human body which usually arises on lysine among the most intensely modified residues. It performs a dynamic role in numerous biological procedures, such as regulation of gene expression, regulation of protein function and RNA processing. Therefore, to identify lysine methylation sites is an important challenge as some experimental procedures are time-consuming.Objective: Herein, we propose a computational predictor named iMethylK_pseAAC to identify lysine methylation sites.Methods: Firstly, we constructed feature vectors based on PseAAC using position and composition rel-ative features and statistical moments. A neural network is trained based on the extracted features. The performance of the proposed method is then validated using cross-validation and jackknife testing.Results: The objective evaluation of the predictor showed accuracy of 96.7% for self-consistency, 91.61% for 10-fold cross-validation and 93.42% for jackknife testing.Conclusion: It is concluded that iMethylK_pseAAC outperforms the counterparts to identify lysine methylation sites such as iMethyl_pseACC, BPB_pPMS and PMeS.

INR-2L: A two-level sequence-based predictor developed via Chou's 5-steps rule and general PseAAC for identifying nuclear receptors and their families

Nuclear receptor proteins (NRPs) perform a vital role in regulating gene expression. With the rapidity growth of NRPs in post-genomic era, it is highly recommendable to identify NRPs and their sub-families accurately from their primary sequences. Several conventional methods have been used for discrimination of NRPs and their sub-families, but did not achieve considerable results. In a sequel, a two-level new computational model “iNR-2 L” is developed. Two discrete methods namely: Dipeptide Composition and Tripeptide Composition were used to formulate NRPs sequences. Further, both the descriptor spaces were merged to construct hybrid space. Furthermore, feature selection technique minimum redundancy and maximum relevance was employed in order to select salient features as well as reduce the noise and redundancy. The experiential outcomes exhibited that the proposed model iNR-2 L achieved outstanding results. It is anticipated that the proposed computational model might be a practical and effective tool for academia and research community.

PLoc_bal-mPlant: Predict Subcellular Localization of Plant Proteins by General PseAAC and Balancing Training Dataset.

Knowledge of protein subcellular localization is vitally important for both basic research and drug development. With the avalanche of protein sequences emerging in the post-genomic age, it is highly desired to develop computational tools for timely and effectively identifying their subcellular localization based on the sequence information alone. Recently, a predictor called "pLoc-mPlant" was developed for identifying the subcellular localization of plant proteins. Its performance is overwhelmingly better than that of the other predictors for the same purpose, particularly in dealing with multi-label systems in which some proteins, called "multiplex proteins", may simultaneously occur in two or more subcellular locations. Although it is indeed a very powerful predictor, more efforts are definitely needed to further improve it. This is because pLoc-mPlant was trained by an extremely skewed dataset in which some subsets (i.e., the protein numbers for some subcellular locations) were more than 10 times larger than the others. Accordingly, it cannot avoid the biased consequence caused by such an uneven training dataset. To overcome such biased consequence, we have developed a new and bias-free predictor called pLoc_bal-mPlant by balancing the training dataset. Cross-validation tests on exactly the same experimentconfirmed dataset have indicated that the proposed new predictor is remarkably superior to pLoc-mPlant, the existing state-of-the-art predictor in identifying the subcellular localization of plant proteins. To maximize the convenience for the majority of experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc_bal-mPlant/, by which users can easily get their desired results without the need to go through the detailed mathematics.

PNitro-Tyr-PseAAC: Predict Nitrotyrosine Sites in Proteins by Incorporating Five Features into Chou's General PseAAC.

Closely related to causes of various diseases such as rheumatoid arthritis, septic shock, and coeliac disease; tyrosine nitration is considered as one of the most important post-translational modification in proteins. Inside a cell, protein modifications occur accurately by the action of sophisticated cellular machinery. Specific enzymes present in endoplasmic reticulum accomplish this task. The identification of potential tyrosine residues in a protein primary sequence, which can be nitrated, is a challenging task. To counter the prevailing, laborious and time-consuming experimental approaches, a novel computational model is introduced in the present study. Based on data collected from experimentally verified tyrosine nitration sites feature vectors are formed. Later, an adaptive training algorithm is used to train a back propagation neural network for prediction purposes. To objectively measure the accuracy of the proposed model, rigorous verification and validation tests are carried out. Through verification and validation, a promising accuracy of 88%, a sensitivity of 85%, a specificity of 89.18% and Mathew's Correlation Coefficient of 0.627 is achieved. It is concluded that the proposed computational model provides the foundation for further investigation and be used for the identification of nitrotyrosine sites in proteins.

IMKPse: Identification of Protein Malonylation Sites by the Key Features Into General PseAAC

Currently, lysine malonylation is treated as one of the most key protein post translational modification in the field of biology and lysine plays a significant role for the regulation of several biological processions. Therefore, accurately identification such modification type will make contributions to understanding their biological processions in this field. The experimental approaches to identify such type of modification sites are time-wasting and laborious in some degree. So, it is necessary and urgent to design and propose computational biology approaches to identify these sites. In this paper, we proposed the IMKPse model that utilized general PseAAC as the classification features and employed flexible neural tree as classification model. In order to deal with the overfitting problem, we utilized the independent datasets of each species. More specifically, such algorithm initially employed amino acid properties from the general PseAAC as the candidate features. With the comparison of candidate features, such a method has the ability to finding out the top five features among them. When evaluated on three data sets in testing set, IMKPse obtained MCC value of 0.9185, 0.9097, and 0.9525 in three species, including E.coli, M.musculus, and H.sapiens, respectively. Meanwhile, IMKPse obtained MCC value of 0.9149, 0.9060, and 0.9467, respectively, in the independent sets. In addition, then, we make some combinations among the top five features. The results demonstrate that the proposed algorithm has superior performances than other approaches. A user-friendly web resource of IMKPSE is available at http://121.250.173.184 .

Identification of protein subcellular localization via integrating evolutionary and physicochemical information into Chou’s general PseAAC

Identifying the location of proteins in a cell plays an important role in understanding their functions, such as drug design, therapeutic target discovery and biological research. However, the traditional subcellular localization experiments are time-consuming, laborious and small scale. With the development of next-generation sequencing technology, the number of proteins has grown exponentially, which lays the foundation of the computational method for identifying protein subcellular localization. Although many methods for predicting subcellular localization of proteins have been proposed, most of them are limited to single-location. In this paper, we propose a multi-kernel SVM to predict subcellular localization of both multi-location and single-location proteins. First, we make use of the evolutionary information extracted from position specific scoring matrix (PSSM) and physicochemical properties of proteins, by Chou’s general PseAAC and other efficient functions. Then, we propose a multi-kernel support vector machine (SVM) model to identify multi-label protein subcellular localization. As a result, our method has a good performance on predicting subcellular localization of proteins. It achieves an average precision of 0.7065 and 0.6889 on two human datasets, respectively. All results are higher than those achieved by other existing methods. Therefore, we provide an efficient system via a novel perspective to study the protein subcellular localization.

Fu-SulfPred: Identification of Protein S-sulfenylation Sites by Fusing Forests via Chou’s General PseAAC

Protein S-sulfenylation is an essential post-translational modification (PTM) that provides critical information to understand molecular mechanisms of cell signaling transduction, stress response and regulation of cellular functions. Recent advancements in computational methods have contributed towards the detection of protein S-sulfenylation sites. However, the performance of identifying protein S-sulfenylation sites can be influenced by a class imbalance of training datasets while the application of various computational methods. In this study, we designed a Fu-SulfPred model using stratified structure of three kinds of decision trees in order to identify possible protein S-sulfenylation sites by means of reconstructing training datasets and sample rescaling technology. Experimental results showed that the correlation coefficient values of Fu-SulfPred model were found to be 0.5437, 0.3736 and 0.6809 on three independent test datasets, respectively, all of which outperformed the Matthews coefficient values of S-SulfPred model. Fu-SulfPred model provides a promising scheme for the identification of protein S-sulfenylation sites and other post-translational modifications.

Prediction and functional analysis of prokaryote lysine acetylation site by incorporating six types of features into Chou's general PseAAC

Lysine acetylation is one of the most important types of protein post-translational modifications (PTM) that are widely involved in cellular regulatory processes. To fully understand the regulatory mechanism of acetylation, identification of acetylation sites is first and most important. However, experimental identification of protein acetylation sites is often time consuming and expensive. Thus, it is popular that predicts PTM sites by computational methods in recent years. Here, we developed a novel method, ProAcePred 2.0, to predict species-specific prokaryote lysine acetylation sites. In this study, we employed an efficient position-specific analysis strategy information gain method to constitute position-specific window of acetylation peptide, and then incorporated different types of features and adopted elastic net algorithm to optimize feature vectors for model learning. The prediction model achieved area under the receiver operating characteristic curve value of six species in training datasets, which are 0.78, 0.752, 0.783, 0.718, 0.839 and 0.826, of Escherichia coli, Corynebacterium glutamicum, Mycobacterium tuberculosis, Bacillus subtilis, S. typhimurium and Geobacillus kaustophilus, respectively. And our method was highly competitive for the majority of species when compared with other methods by using independent test datasets. In addition, function analyses demonstrated that different organisms were preferentially involved in different biological processes and pathways. The detailed analyses in this paper could help us to understand more of the acetylation mechanism and provide guidance for the related experimental validation. A user-friendly online web service of ProAcePred 2.0 can be freely available at http://computbiol.ncu.edu.cn/PAPred.

Effective DNA binding protein prediction by using key features via Chou’s general PseAAC

DNA-binding proteins (DBPs) are responsible for several cellular functions, starting from our immunity system to the transport of oxygen. In the recent studies, scientists have used supervised machine learning based methods that use information from the protein sequence only to classify the DBPs. Most of the methods work effectively on the train sets but performance of most of them degrades in the independent test set. It shows a room for improving the prediction method by reducing over-fitting. In this paper, we have extracted several features solely using the protein sequence and carried out two different types of feature selection on them. Our results have proven comparable on training set and significantly improved on the independent test set. On the independent test set our accuracy was 82.26% which is 1.62% improved compared to the previous best state-of-the-art methods. Performance in terms of sensitivity and area under receiver operating characteristic curve for the independent test set was also higher and they were 0.95 and 0.823 respectively.

Predicting membrane proteins and their types by extracting various sequence features into Chou's general PseAAC.

For many biological functions membrane proteins (MPs) are considered crucial. Due to this nature of MPs, many pharmaceutical agents have reflected them as attractive targets. It bears indispensable importance that MPs are predicted with accurate measures using effective and efficient computational models (CMs). Annotation of MPs using in vitro analytical techniques is time-consuming and expensive; and in some cases, it can prove to be intractable. Due to this scenario, automated prediction and annotation of MPs through CM based techniques have appeared to be useful. Based on the use of computational intelligence and statistical moments based feature set, an MP prediction framework is proposed. Furthermore, the previously used dataset has been enhanced by incorporating new MPs from the latest release of UniProtKB. Rigorous experimentation proves that the use of statistical moments with a multilayer neural network, trained using back-propagation based prediction techniques allows more thorough results.

PLoc_bal-mGneg: Predict subcellular localization of Gram-negative bacterial proteins by quasi-balancing training dataset and general PseAAC

One of the hottest topics in molecular cell biology is to determine the subcellular localization of proteins from various different organisms. This is because it is crucially important for both basic research and drug development. Recently, a predictor called “pLoc-mGneg” was developed for identifying the subcellular localization of Gram-negative bacterial proteins. Its performance is overwhelmingly better than that of the other predictors for the same purpose, particularly in dealing with multi-label systems in which some proteins, called “multiplex proteins”, may simultaneously occur in two or more subcellular locations. Although it is indeed a very powerful predictor, more efforts are definitely needed to further improve it. This is because pLoc-mGneg was trained by an extremely skewed dataset in which some subset (subcellular location) was about 5 to 70 times the size of the other subsets. Accordingly, it cannot avoid the biased consequence caused by such an uneven training dataset. To alleviate such a consequence, we have developed a new and bias-reducing predictor called pLoc_bal-mGneg by quasi-balancing the training dataset. Cross-validation tests on exactly the same experiment-confirmed dataset have indicated that the proposed new predictor is remarkably superior to pLoc-mGneg, the existing state-of-the-art predictor in identifying the subcellular localization of Gram-negative bacterial proteins. To maximize the convenience for most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc_bal-mGneg/, by which users can easily get their desired results without the need to go through the detailed mathematics.

BlaPred: Predicting and classifying β-lactamase using a 3-tier prediction system via Chou's general PseAAC

Antibiotics of β-lactam class account for nearly half of the global antibiotic use. The β-lactamase enzyme is a major element of the bacterial arsenals to escape the lethal effect of β-lactam antibiotics. Different variants of β-lactamases have evolved to counter the different types of β-lactam antibiotics. Extensive research has been done to isolate and characterize different variants of β-lactamases. Unfortunately, identification and classification of the β-lactamase enzyme are purely based on experiments, which is both time- and resource-consuming. Thus, there is a need for fast and accurate computational methods to identify and classify new β-lactamase enzymes from the avalanche of sequence data generated in the post-genomic era. Based on these considerations, we have developed a support vector machine based three-tier prediction system, BlaPred, to predict and classify (as per Ambler classification) β-lactamases solely from their protein sequences. The input features used were amino acid composition, classic and amphiphilic pseudo amino acid compositions. The results show that the classic pseudo amino acid composition-based models performed better than the other models. Following a leave-one-out cross-validation procedure, the accuracy to discriminate β-lactamases from non-β-lactamases was 93.57% (tier-I); accuracies for prediction of class A β-lactamases was 93.27%, 95.52% for class B, 96.86% for class C and 97.31% for class D (tier-II); and at tier-III the accuracies for prediction were 84.78%, 95.65% and 89.13% for subclasses B1, B2 and B3, respectively. The comparative results on an independent dataset suggests that our method works efficiently to distinguish β-lactamases from non-β-lactamases, with an overall accuracy of 93.09%, and is further able to classify β-lactamase sequences into their respective Ambler classes and subclasses with accuracy higher than 92% and 87%, respectively. Comparative performance of BlaPred on an independent benchmark dataset also shows a significant improvement over other existing methods. Finally, BlaPred is available as a webserver, as well as standalone software, which can be accessed at http://proteininformatics.org/mkumar/blapred.

Predicting membrane protein types by incorporating a novel feature set into Chou's general PseAAC

Membrane proteins are vital type of proteins that serve as channels, receptors and energy transducers in a cell. They perform various important functions, which are mainly associated with their types. They are also attractive targets of drug discovery for various diseases. So predicting membrane protein types is a crucial and challenging research area in bioinformatics and proteomics. Because of vast investigation of uncharacterized protein sequences in databases, customary biophysical techniques are extremely tedious, costly and vulnerable to mistakes. Subsequently, it is very attractive to build a vigorous, solid, proficient technique to predict membrane protein types. In this work, a novel feature set Exchange Group Based Protein Sequence Representation (EGBPSR) is proposed for classification of membrane proteins with two new feature extraction strategies known as Exchange Group Local Pattern (EGLP) and Amino acid Interval Pattern (AIP). Imbalanced dataset and large dataset are often handled well by decision tree classifiers. Since imbalanced dataset are taken, the performance of various decision tree classifiers such as Decision Tree (DT), Classification and Regression Tree (CART), ensemble methods such as Adaboost, Random Under Sampling (RUS) boost, Rotation forest and Random forest are analyzed. The overall accuracy achieved in predicting membrane protein types is 96.45%.

Predicting structural classes of proteins by incorporating their global and local physicochemical and conformational properties into general Chou's PseAAC

In this study, I introduce novel global and local 0D-protein descriptors based on a statistical quantity named Total Sum of Squares (TSS). This quantity represents the sum of the squares differences of amino acid properties from the arithmetic mean property. As an extension, the amino acid-types and amino acid-groups formalisms are used for describing zones of interest in proteins. To assess the effectiveness of the proposed descriptors, a Nearest Neighbor model for predicting the major four protein structural classes was built. This model has a success rate of 98.53% on the jackknife cross-validation test; this performance being superior to other reported methods despite the simplicity of the predictor. Additionally, this predictor has an average success rate of 98.35% in different cross-validation tests performed. A value of 0.98 for the Kappa statistic clearly discriminates this model from a random predictor. The results obtained by the Nearest Neighbor model demonstrated the ability of the proposed descriptors not only to reflect relevant biochemical information related to the structural classes of proteins but also to allow appropriate interpretability. It can thus be expected that the current method may play a supplementary role to other existing approaches for protein structural class prediction and other protein attributes.

Identify Gram-negative bacterial secreted protein types by incorporating different modes of PSSM into Chou’s general PseAAC via Kullback–Leibler divergence

Gram-negative bacterial secreted proteins are crucial for bacterial pathogenesis by making bacteria interact with their environments. Therefore, identification of bacterial secreted proteins becomes a significant process for the research of various diseases and the corresponding drugs. In this paper, we develop a feature design model named ACCP-KL-NMF by fusing PSSM-based auto-cross correlation analysis for features extraction and nonnegative matrix factorization algorithm based on Kullback–Leibler divergence for dimensionality reduction. Hence, a 150-dimensional feature vector is constructed on the training set. Then support vector machine is adopted as the classifier, and the most objective jackknife test is chosen for evaluating the accuracy. The ACCP-KL-NMF model yields the approving performance of the overall accuracy on the test set, and also outperforms the other three existing models. The numerical experimental results show that our model is effective and reliable for identification of Gram-negative bacterial secreted protein types. Moreover, it is anticipated that the proposed model could be beneficial for other biology sequence in future research.