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1.
Elucidation of signaling events in a pathogen is potentially important to tackle the infection caused by it. Such events mediated by protein phosphorylation play important roles in infection, and therefore, to predict the phosphosites and substrates of the serine/threonine protein kinases, we have developed a Machine learning-based approach for Mycobacterium tuberculosis serine/threonine protein kinases using kinase-peptide structure–sequence data. This approach utilizes features derived from kinase three-dimensional-structure environment and known phosphosite sequences to generate support vector machine (SVM)-based kinase-specific predictions of phosphosites of serine/threonine protein kinases (STPKs) with no or scarce data of their substrates. SVM outperformed the four machine learning algorithms we tried (random forest, logistic regression, SVM, and k-nearest neighbors) with an area under the curve receiver-operating characteristic value of 0.88 on the independent testing dataset and a 10-fold cross-validation accuracy of ~81.6% for the final model. Our predicted phosphosites of M. tuberculosis STPKs form a useful resource for experimental biologists enabling elucidation of STPK mediated posttranslational regulation of important cellular processes.  相似文献   

2.
选择性剪切是调解基因表达的重要机制.识别选择性剪切位点是后基因组时代的一个重要工作.本文从最新的EBI人类基因选择性剪切数据库中,选取5'/3'选择性剪切位点作为正集,选取在剪切位点附近的假剪切位点作为负集,并把所有的选择性剪切位点和假剪切位点随机分成训练集和测试集.本文选用的预测选择性剪切位点的方法是基于位置权重矩阵和离散增量的支持向量机方法.此方法仅基于训练集,以不同位点的单碱基概率和序列片断的三联体频数作为信息参数,利用位置权重矩阵和离散增量算法结合支持向量机,得到了选择性供体位点和受体位点的分类器,并用此分类器对测试集中的选择性供体位点和受体位点进行预测.对独立测试集中的选择性供体位点和选择性受体位点的预测成功率分别为88.74%和90.86%,特异性分别为85.62%和81.19%.本文预测选择性剪切位点的方法成功率高于其它选择性剪切位点预测方法预测成功率,此预测方法进一步提高了对选择性剪切位点的理论预测能力.  相似文献   

3.
4.
Protein–protein interactions are intrinsic to virtually every cellular process. Predicting the binding affinity of protein–protein complexes is one of the challenging problems in computational and molecular biology. In this work, we related sequence features of protein–protein complexes with their binding affinities using machine learning approaches. We set up a database of 185 protein–protein complexes for which the interacting pairs are heterodimers and their experimental binding affinities are available. On the other hand, we have developed a set of 610 features from the sequences of protein complexes and utilized Ranker search method, which is the combination of Attribute evaluator and Ranker method for selecting specific features. We have analyzed several machine learning algorithms to discriminate protein‐protein complexes into high and low affinity groups based on their Kd values. Our results showed a 10‐fold cross‐validation accuracy of 76.1% with the combination of nine features using support vector machines. Further, we observed accuracy of 83.3% on an independent test set of 30 complexes. We suggest that our method would serve as an effective tool for identifying the interacting partners in protein–protein interaction networks and human–pathogen interactions based on the strength of interactions. Proteins 2014; 82:2088–2096. © 2014 Wiley Periodicals, Inc.  相似文献   

5.
We present a novel partner‐specific protein–protein interaction site prediction method called PAIRpred. Unlike most existing machine learning binding site prediction methods, PAIRpred uses information from both proteins in a protein complex to predict pairs of interacting residues from the two proteins. PAIRpred captures sequence and structure information about residue pairs through pairwise kernels that are used for training a support vector machine classifier. As a result, PAIRpred presents a more detailed model of protein binding, and offers state of the art accuracy in predicting binding sites at the protein level as well as inter‐protein residue contacts at the complex level. We demonstrate PAIRpred's performance on Docking Benchmark 4.0 and recent CAPRI targets. We present a detailed performance analysis outlining the contribution of different sequence and structure features, together with a comparison to a variety of existing interface prediction techniques. We have also studied the impact of binding‐associated conformational change on prediction accuracy and found PAIRpred to be more robust to such structural changes than existing schemes. As an illustration of the potential applications of PAIRpred, we provide a case study in which PAIRpred is used to analyze the nature and specificity of the interface in the interaction of human ISG15 protein with NS1 protein from influenza A virus. Python code for PAIRpred is available at http://combi.cs.colostate.edu/supplements/pairpred/ . Proteins 2014; 82:1142–1155. © 2013 Wiley Periodicals, Inc.  相似文献   

6.
Prediction of RNA binding sites in a protein using SVM and PSSM profile   总被引:1,自引:0,他引:1  
Kumar M  Gromiha MM  Raghava GP 《Proteins》2008,71(1):189-194
  相似文献   

7.
Lysine acetylation is an essentially reversible and high regulated post-translational modification which regulates diverse protein properties. Experimental identification of acetylation sites is laborious and expensive. Hence, there is significant interest in the development of computational methods for reliable prediction of acetylation sites from amino acid sequences. In this paper we use an ensemble of support vector machine classifiers to perform this work. The experimentally determined acetylation lysine sites are extracted from Swiss-Prot database and scientific literatures. Experiment results show that an ensemble of support vector machine classifiers outperforms single support vector machine classifier and other computational methods such as PAIL and LysAcet on the problem of predicting acetylation lysine sites. The resulting method has been implemented in EnsemblePail, a web server for lysine acetylation sites prediction available at http://www.aporc.org/EnsemblePail/.  相似文献   

8.
Zhu Y  Li T  Li D  Zhang Y  Xiong W  Sun J  Tang Z  Chen G 《Amino acids》2012,42(5):1749-1755
Numerous methods for predicting γ-turns in proteins have been developed. However, the results they generally provided are not very good, with a Matthews correlation coefficient (MCC) ≤0.18. Here, an attempt has been made to develop a method to improve the accuracy of γ-turn prediction. First, we employ the geometric mean metric as optimal criterion to evaluate the performance of support vector machine for the highly imbalanced γ-turn dataset. This metric tries to maximize both the sensitivity and the specificity while keeping them balanced. Second, a predictor to generate protein shape string by structure alignment against the protein structure database has been designed and the predicted shape string is introduced as new variable for γ-turn prediction. Based on this perception, we have developed a new method for γ-turn prediction. After training and testing the benchmark dataset of 320 non-homologous protein chains using a fivefold cross-validation technique, the present method achieves excellent performance. The overall prediction accuracy Q total can achieve 92.2% and the MCC is 0.38, which outperform the existing γ-turn prediction methods. Our results indicate that the protein shape string is useful for predicting protein tight turns and it is reasonable to use the dihedral angle information as a variable for machine learning to predict protein folding. The dataset used in this work and the software to generate predicted shape string from structure database can be obtained from anonymous ftp site freely.  相似文献   

9.

Background  

Predicting the binding sites between two interacting proteins provides important clues to the function of a protein. Recent research on protein binding site prediction has been mainly based on widely known machine learning techniques, such as artificial neural networks, support vector machines, conditional random field, etc. However, the prediction performance is still too low to be used in practice. It is necessary to explore new algorithms, theories and features to further improve the performance.  相似文献   

10.
Predicting protein–protein interactions (PPIs) is a challenging task and essential to construct the protein interaction networks, which is important for facilitating our understanding of the mechanisms of biological systems. Although a number of high‐throughput technologies have been proposed to predict PPIs, there are unavoidable shortcomings, including high cost, time intensity, and inherently high false positive rates. For these reasons, many computational methods have been proposed for predicting PPIs. However, the problem is still far from being solved. In this article, we propose a novel computational method called RVM‐BiGP that combines the relevance vector machine (RVM) model and Bi‐gram Probabilities (BiGP) for PPIs detection from protein sequences. The major improvement includes (1) Protein sequences are represented using the Bi‐gram probabilities (BiGP) feature representation on a Position Specific Scoring Matrix (PSSM), in which the protein evolutionary information is contained; (2) For reducing the influence of noise, the Principal Component Analysis (PCA) method is used to reduce the dimension of BiGP vector; (3) The powerful and robust Relevance Vector Machine (RVM) algorithm is used for classification. Five‐fold cross‐validation experiments executed on yeast and Helicobacter pylori datasets, which achieved very high accuracies of 94.57 and 90.57%, respectively. Experimental results are significantly better than previous methods. To further evaluate the proposed method, we compare it with the state‐of‐the‐art support vector machine (SVM) classifier on the yeast dataset. The experimental results demonstrate that our RVM‐BiGP method is significantly better than the SVM‐based method. In addition, we achieved 97.15% accuracy on imbalance yeast dataset, which is higher than that of balance yeast dataset. The promising experimental results show the efficiency and robust of the proposed method, which can be an automatic decision support tool for future proteomics research. For facilitating extensive studies for future proteomics research, we developed a freely available web server called RVM‐BiGP‐PPIs in Hypertext Preprocessor (PHP) for predicting PPIs. The web server including source code and the datasets are available at http://219.219.62.123:8888/BiGP/ .  相似文献   

11.
Hwang H  Vreven T  Whitfield TW  Wiehe K  Weng Z 《Proteins》2011,79(8):2467-2474
Proteins often undergo conformational changes when binding to each other. A major fraction of backbone conformational changes involves motion on the protein surface, particularly in loops. Accounting for the motion of protein surface loops represents a challenge for protein-protein docking algorithms. A first step in addressing this challenge is to distinguish protein surface loops that are likely to undergo backbone conformational changes upon protein-protein binding (mobile loops) from those that are not (stationary loops). In this study, we developed a machine learning strategy based on support vector machines (SVMs). Our SVM uses three features of loop residues in the unbound protein structures-Ramachandran angles, crystallographic B-factors, and relative accessible surface area-to distinguish mobile loops from stationary ones. This method yields an average prediction accuracy of 75.3% compared with a random prediction accuracy of 50%, and an average of 0.79 area under the receiver operating characteristic (ROC) curve using cross-validation. Testing the method on an independent dataset, we obtained a prediction accuracy of 70.5%. Finally, we applied the method to 11 complexes that involve members from the Ras superfamily and achieved prediction accuracy of 92.8% for the Ras superfamily proteins and 74.4% for their binding partners.  相似文献   

12.
Ho SY  Yu FC  Chang CY  Huang HL 《Bio Systems》2007,90(1):234-241
In this paper, we investigate the design of accurate predictors for DNA-binding sites in proteins from amino acid sequences. As a result, we propose a hybrid method using support vector machine (SVM) in conjunction with evolutionary information of amino acid sequences in terms of their position-specific scoring matrices (PSSMs) for prediction of DNA-binding sites. Considering the numbers of binding and non-binding residues in proteins are significantly unequal, two additional weights as well as SVM parameters are analyzed and adopted to maximize net prediction (NP, an average of sensitivity and specificity) accuracy. To evaluate the generalization ability of the proposed method SVM-PSSM, a DNA-binding dataset PDC-59 consisting of 59 protein chains with low sequence identity on each other is additionally established. The SVM-based method using the same six-fold cross-validation procedure and PSSM features has NP=80.15% for the training dataset PDNA-62 and NP=69.54% for the test dataset PDC-59, which are much better than the existing neural network-based method by increasing the NP values for training and test accuracies up to 13.45% and 16.53%, respectively. Simulation results reveal that SVM-PSSM performs well in predicting DNA-binding sites of novel proteins from amino acid sequences.  相似文献   

13.
Binding sites in proteins can be either specifically functional binding sites (active sites) that bind specific substrates with high affinity or regulatory binding sites (allosteric sites), that modulate the activity of functional binding sites through effector molecules. Owing to their significance in determining protein function, the identification of protein functional and regulatory binding sites is widely acknowledged as an important biological problem. In this work, we present a novel binding site prediction method, Active and Regulatory site Prediction (AR-Pred), which supplements protein geometry, evolutionary, and physicochemical features with information about protein dynamics to predict putative active and allosteric site residues. As the intrinsic dynamics of globular proteins plays an essential role in controlling binding events, we find it to be an important feature for the identification of protein binding sites. We train and validate our predictive models on multiple balanced training and validation sets with random forest machine learning and obtain an ensemble of discrete models for each prediction type. Our models for active site prediction yield a median area under the curve (AUC) of 91% and Matthews correlation coefficient (MCC) of 0.68, whereas the less well-defined allosteric sites are predicted at a lower level with a median AUC of 80% and MCC of 0.48. When tested on an independent set of proteins, our models for active site prediction show comparable performance to two existing methods and gains compared to two others, while the allosteric site models show gains when tested against three existing prediction methods. AR-Pred is available as a free downloadable package at https://github.com/sambitmishra0628/AR-PRED_source .  相似文献   

14.
Protein structure can provide new insight into the biological function of a protein and can enable the design of better experiments to learn its biological roles. Moreover, deciphering the interactions of a protein with other molecules can contribute to the understanding of the protein's function within cellular processes. In this study, we apply a machine learning approach for classifying RNA-binding proteins based on their three-dimensional structures. The method is based on characterizing unique properties of electrostatic patches on the protein surface. Using an ensemble of general protein features and specific properties extracted from the electrostatic patches, we have trained a support vector machine (SVM) to distinguish RNA-binding proteins from other positively charged proteins that do not bind nucleic acids. Specifically, the method was applied on proteins possessing the RNA recognition motif (RRM) and successfully classified RNA-binding proteins from RRM domains involved in protein-protein interactions. Overall the method achieves 88% accuracy in classifying RNA-binding proteins, yet it cannot distinguish RNA from DNA binding proteins. Nevertheless, by applying a multiclass SVM approach we were able to classify the RNA-binding proteins based on their RNA targets, specifically, whether they bind a ribosomal RNA (rRNA), a transfer RNA (tRNA), or messenger RNA (mRNA). Finally, we present here an innovative approach that does not rely on sequence or structural homology and could be applied to identify novel RNA-binding proteins with unique folds and/or binding motifs.  相似文献   

15.
16.
Large efforts have been made in classifying residues as binding sites in proteins using machine learning methods. The prediction task can be translated into the computational challenge of assigning each residue the label binding site or non‐binding site. Observational data comes from various possibly highly correlated sources. It includes the structure of the protein but not the structure of the complex. The model class of conditional random fields (CRFs) has previously successfully been used for protein binding site prediction. Here, a new CRF‐approach is presented that models the dependencies of residues using a general graphical structure defined as a neighborhood graph and thus our model makes fewer independence assumptions on the labels than sequential labeling approaches. A novel node feature “change in free energy” is introduced into the model, which is then denoted by ΔF‐CRF. Parameters are trained with an online large‐margin algorithm. Using the standard feature class relative accessible surface area alone, the general graph‐structure CRF already achieves higher prediction accuracy than the linear chain CRF of Li et al. ΔF‐CRF performs significantly better on a large range of false positive rates than the support‐vector‐machine‐based program PresCont of Zellner et al. on a homodimer set containing 128 chains. ΔF‐CRF has a broader scope than PresCont since it is not constrained to protein subgroups and requires no multiple sequence alignment. The improvement is attributed to the advantageous combination of the novel node feature with the standard feature and to the adopted parameter training method. Proteins 2015; 83:844–852. © 2015 Wiley Periodicals, Inc.  相似文献   

17.
Transient protein–protein interactions play a vital role in many biological processes, such as cell regulation and signal transduction. A nonredundant dataset of 130 protein chains extracted from transient complexes was used to analyze the features of transient interfaces. It was found that besides the two well-known features, sequence profile and accessible surface area (ASA), the temperature factor (B-factor) can also reflect the differences between interface and the rest of protein surface. These features were utilized to construct support vector machine (SVM) classifiers to identify interaction sites. The results of threefold cross-validation on the nonredundant dataset show that when B-factor was used as an additional feature, the prediction performance can be improved significantly. The sensitivity, specificity and correlation coefficient were raised from 54 to 62%, 41 to 45% and 0.20 to 0.29, respectively. To further illustrate the effectiveness of our method, the classifiers were tested with an independent set of 53 nonhomologous protein chains derived from benchmark 2.0. The sensitivity, specificity and correlation coefficient of the classifier based on the three features were 63%, 45% and 0.33, respectively. It is indicated that our classifiers are robust and can be applied to complement experimental techniques in studying transient protein–protein interactions.  相似文献   

18.
Protein–protein interactions are a fundamental aspect of many biological processes. The advent of recombinant protein and computational techniques has allowed for the rational design of proteins with novel binding capabilities. It is therefore desirable to predict which designed proteins are capable of binding in vitro. To this end, we have developed a learned classification model that combines energetic and non‐energetic features. Our feature set is adapted from specialized potentials for aromatic interactions, hydrogen bonds, electrostatics, shape, and desolvation. A binding model built on these features was initially developed for CAPRI Round 21, achieving top results in the independent assessment. Here, we present a more thoroughly trained and validated model, and compare various support‐vector machine kernels. The Gaussian kernel model classified both high‐resolution complexes and designed nonbinders with 79–86% accuracy on independent test data. We also observe that multiple physical potentials for dielectric‐dependent electrostatics and hydrogen bonding contribute to the enhanced predictive accuracy, suggesting that their combined information is much greater than that of any single energetics model. We also study the change in predictive performance as the model features or training data are varied, observing unusual patterns of prediction in designed interfaces as compared with other data types. Proteins 2013; 81:1919–1930. © 2013 Wiley Periodicals, Inc.  相似文献   

19.
基于支持向量机的蛋白质同源寡聚体分类研究   总被引:14,自引:1,他引:13  
基于支持向量机和贝叶斯方法,从蛋白质一级序列出发对蛋白质同源二聚体、同源三聚体、同源四聚体、同源六聚体进行分类研究,结果表明:基于支持向量机, 采用“一对多”和“一对一”策略, 其分类总精度分别为77.36%和93.43%, 分别比基于贝叶斯协方差判别法的分类总精度50.64%提高26.72和42.79个百分点.从而说明支持向量机可用于蛋白质同源寡聚体分类,且是一种非常有效的方法.对于多类蛋白质同源寡聚体分类,基于相同的机器学习方法(如支持向量机),采用“一对一”策略比“一对多”效果好.同时亦表明蛋白质同源寡聚体一级序列包含四级结构信息.  相似文献   

20.
Attachment of a myristoyl group to NH(2)-terminus of a nascent protein among protein post-translational modification (PTM) is called myristoylation. The myristate moiety of proteins plays an important role for their biological functions, such as regulation of membrane binding (HIV-1 Gag) and enzyme activity (AMPK). Several predictors based on protein sequences alone are hitherto proposed. However, they produce a great number of false positive and false negative predictions; or they cannot be used for general purpose (i.e., taxon-specific); or threshold values of the decision rule of predictors need to be selected with cautiousness. Here, we present novel and taxon-free predictors based on protein primary structure. To identify myristoylated proteins accurately, we employ a widely used machinelearning algorithm, support vector machine (SVM). A series of SVM predictors are developed in the present study where various scales representing physicochemical and biological properties of amino acids (from the AAindex database) are used for numerical transformation of protein sequences. Of the predictors, the top ten achieve accuracies of >98% (the average value is 98.34%), and also the area under the ROC curve (AUC) values of >0.98. Compared with those of previous studies, the prediction accuracies are improved by about 3 to 4%.  相似文献   

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