Dataset Information

Computational prediction of molecular pathogen-host interactions based on dual transcriptome data.

ABSTRACT: Inference of inter-species gene regulatory networks based on gene expression data is an important computational method to predict pathogen-host interactions (PHIs). Both the experimental setup and the nature of PHIs exhibit certain characteristics. First, besides an environmental change, the battle between pathogen and host leads to a constantly changing environment and thus complex gene expression patterns. Second, there might be a delay until one of the organisms reacts. Third, toward later time points only one organism may survive leading to missing gene expression data of the other organism. Here, we account for PHI characteristics by extending NetGenerator, a network inference tool that predicts gene regulatory networks from gene expression time series data. We tested multiple modeling scenarios regarding the stimuli functions of the interaction network based on a benchmark example. We show that modeling perturbation of a PHI network by multiple stimuli better represents the underlying biological phenomena. Furthermore, we utilized the benchmark example to test the influence of missing data points on the inference performance. Our results suggest that PHI network inference with missing data is possible, but we recommend to provide complete time series data. Finally, we extended the NetGenerator tool to incorporate gene- and time point specific variances, because complex PHIs may lead to high variance in expression data. Sample variances are directly considered in the objective function of NetGenerator and indirectly by testing the robustness of interactions based on variance dependent disturbance of gene expression values. We evaluated the method of variance incorporation on dual RNA sequencing (RNA-Seq) data of Mus musculus dendritic cells incubated with Candida albicans and proofed our method by predicting previously verified PHIs as robust interactions.

SUBMITTER: Schulze S

PROVIDER: S-EPMC4319478 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Computational prediction of molecular pathogen-host interactions based on dual transcriptome data.

Schulze Sylvie S Henkel Sebastian G SG Driesch Dominik D Guthke Reinhard R Linde Jörg J

Frontiers in microbiology 20150206

Inference of inter-species gene regulatory networks based on gene expression data is an important computational method to predict pathogen-host interactions (PHIs). Both the experimental setup and the nature of PHIs exhibit certain characteristics. First, besides an environmental change, the battle between pathogen and host leads to a constantly changing environment and thus complex gene expression patterns. Second, there might be a delay until one of the organisms reacts. Third, toward later ti ...[more]

PMID: 25705211

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Project description:BACKGROUND:Subunit vaccines based on recombinant proteins have been effective in preventing infectious diseases and are expected to meet the demands of future vaccine development. Computational approach, especially reverse vaccinology (RV) method has enormous potential for identification of protein vaccine candidates (PVCs) from a proteome. The existing protective antigen prediction software and web servers have low prediction accuracy leading to limited applications for vaccine development. Besides machine learning techniques, those software and web servers have considered only protein's adhesin-likeliness as criterion for identification of PVCs. Several non-adhesin functional classes of proteins involved in host-pathogen interactions and pathogenesis are known to provide protection against bacterial infections. Therefore, knowledge of bacterial pathogenesis has potential to identify PVCs. RESULTS:A web server, Jenner-Predict, has been developed for prediction of PVCs from proteomes of bacterial pathogens. The web server targets host-pathogen interactions and pathogenesis by considering known functional domains from protein classes such as adhesin, virulence, invasin, porin, flagellin, colonization, toxin, choline-binding, penicillin-binding, transferring-binding, fibronectin-binding and solute-binding. It predicts non-cytosolic proteins containing above domains as PVCs. It also provides vaccine potential of PVCs in terms of their possible immunogenicity by comparing with experimentally known IEDB epitopes, absence of autoimmunity and conservation in different strains. Predicted PVCs are prioritized so that only few prospective PVCs could be validated experimentally. The performance of web server was evaluated against known protective antigens from diverse classes of bacteria reported in Protegen database and datasets used for VaxiJen server development. The web server efficiently predicted known vaccine candidates reported from Streptococcus pneumoniae and Escherichia coli proteomes. The Jenner-Predict server outperformed NERVE, Vaxign and VaxiJen methods. It has sensitivity of 0.774 and 0.711 for Protegen and VaxiJen dataset, respectively while specificity of 0.940 has been obtained for the latter dataset. CONCLUSIONS:Better prediction accuracy of Jenner-Predict web server signifies that domains involved in host-pathogen interactions and pathogenesis are better criteria for prediction of PVCs. The web server has successfully predicted maximum known PVCs belonging to different functional classes. Jenner-Predict server is freely accessible at http://117.211.115.67/vaccine/home.html.

Project description:Experimental approaches are currently used to determine viral-host interactions, but these approaches are both time-consuming and costly. For these reasons, computational-based approaches are recommended. In this study, using computational-based approaches, viral-host interactions of SARS-CoV-2 virus and human proteins were predicted. The study consists of four different stages; in the first stage viral and host protein sequences were obtained. In the second stage, protein sequences were converted into numerical expressions by various protein mapping methods. These methods are entropy-based, AVL-tree, FIBHASH, binary encoding, CPNR, PAM250, BLOSUM62, Atchley factors, Meiler parameters, EIIP, AESNN1, Miyazawa energies, Micheletti potentials, Z-scale, and hydrophobicity. In the third stage, a deep learning model was designed and BiLSTM was used for this. In the last stage, the protein sequences were classified, and the viral-host interactions were predicted. The performances of protein mapping methods were determined by accuracy, F1-score, specificity, sensitivity, and AUC scores. According to the classification results, the best classification process was obtained by the entropy-based method. With this method, 94.74% accuracy, and 0.95 AUC score were calculated. Then, the most successful classification process was performed with the Z-scale and 91.23% accuracy, and 0.96 AUC score were obtained. Although other protein mapping methods are not as efficient as Z-scale and entropy-based methods, they have achieved successful classification. AVL-tree, FIBHASH, binary encoding, CPNR, PAM250, BLOSUM62, Atchley factors, Meiler parameters and AESNN1 methods showed over 80% accuracy, F1-score, and AUC score. Accuracy scores of EIIP, Miyazawa energies, Micheletti potentials and hydrophobicity methods remained below 80%. When the results were examined in general, it was observed that the computational approaches were successful in predicting viral-host interactions between SARS-CoV-2 virus and human proteins.

Dataset Information

Computational prediction of molecular pathogen-host interactions based on dual transcriptome data.

Publications

Computational prediction of molecular pathogen-host interactions based on dual transcriptome data.

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