Abstract
BackgroundPrediction of bacterial virulent protein sequences has implications for identification and characterization of novel virulence-associated factors, finding novel drug/vaccine targets against proteins indispensable to pathogenicity, and understanding the complex virulence mechanism in pathogens.ResultsIn the present study we propose a bacterial virulent protein prediction method based on bi-layer cascade Support Vector Machine (SVM). The first layer SVM classifiers were trained and optimized with different individual protein sequence features like amino acid composition, dipeptide composition (occurrences of the possible pairs of ith and i+1th amino acid residues), higher order dipeptide composition (pairs of ith and i+2nd residues) and Position Specific Iterated BLAST (PSI-BLAST) generated Position Specific Scoring Matrices (PSSM). In addition, a similarity-search based module was also developed using a dataset of virulent and non-virulent proteins as BLAST database. A five-fold cross-validation technique was used for the evaluation of various prediction strategies in this study. The results from the first layer (SVM scores and PSI-BLAST result) were cascaded to the second layer SVM classifier to train and generate the final classifier. The cascade SVM classifier was able to accomplish an accuracy of 81.8%, covering 86% area in the Receiver Operator Characteristic (ROC) plot, better than that of either of the layer one SVM classifiers based on single or multiple sequence features.ConclusionVirulentPred is a SVM based method to predict bacterial virulent proteins sequences, which can be used to screen virulent proteins in proteomes. Together with experimentally verified virulent proteins, several putative, non annotated and hypothetical protein sequences have been predicted to be high scoring virulent proteins by the prediction method. VirulentPred is available as a freely accessible World Wide Web server – VirulentPred, at http://bioinfo.icgeb.res.in/virulent/.
Highlights
Prediction of bacterial virulent protein sequences has implications for identification and characterization of novel virulence-associated factors, finding novel drug/vaccine targets against proteins indispensable to pathogenicity, and understanding the complex virulence mechanism in pathogens
Colonization factors are a class of proteins, which enables certain bacteria to colonize within the host cells, for example Helicobacter pylori survives in the acidic milieu of the human stomach by producing urease enzyme, which catalyzes the formation of carbon dioxide and ammonia that can neutralize the acidic pH
Algorithm Composition based Support Vector Machine (SVM) classifiers Firstly, we evaluated the SVM classifiers trained and optimized with amino acid compositions (AAC) features – developed with linear, polyno
Summary
Prediction of bacterial virulent protein sequences has implications for identification and characterization of novel virulence-associated factors, finding novel drug/vaccine targets against proteins indispensable to pathogenicity, and understanding the complex virulence mechanism in pathogens. Virulence of a bacterial pathogen is its relative ability to cause a disease usually described in terms of number of infecting bacteria, the route of its entry into the host body and intrinsic bacterial virulence factors. Adhesins belong to an important class of bacterial proteins, which play an important role in the process of adherence of bacteria to the host cells. Colonization factors are a class of proteins, which enables certain bacteria to colonize within the host cells, for example Helicobacter pylori survives in the acidic milieu of the human stomach by producing urease enzyme, which catalyzes the formation of carbon dioxide and ammonia that can neutralize the acidic pH. Other elements such as cell surface carbohydrates and proteins that protect pathogens from host defense mechanisms are included in the class of defensive virulence factors which includes capsular polysaccharides, lipopolysaccharides and outer membrane proteins. Apart from these, there are other virulence traits which are indirectly involved in virulence, such as secretory machineries, siderophores, catalases and regulators; which are essential for pathogens to manifest infection [3]
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