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
Multi-omics has the promise to provide a detailed molecular picture of biological systems. Although obtaining multi-omics data is relatively easy, methods that analyze such data have been lagging. In this paper, we present an algorithm that uses probabilistic graph representations and external knowledge to perform optimal structure learning and deduce a multifarious interaction network for multi-omics data from a bacterial community. Kefir grain, a microbial community that ferments milk and creates kefir, represents a self-renewing, stable, natural microbial community. Kefir has been shown to have a wide range of health benefits. We obtained a controlled bacterial community using the two most abundant and well-studied species in kefir grains: Lentilactobacillus kefiri and Lactobacillus kefiranofaciens. We applied growth temperatures of 30 °C and 37 °C and obtained transcriptomic, metabolomic, and proteomic data for the same 20 samples (10 samples per temperature). We obtained a multi-omics interaction network, which generated insights that would not have been possible with single-omics analysis. We identified interactions among transcripts, proteins, and metabolites, suggesting active toxin/antitoxin systems. We also observed multifarious interactions that involved the shikimate pathway. These observations helped explain bacterial adaptation to different stress conditions, co-aggregation, and increased activation of L. kefiranofaciens at 37 °C.