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Bacterial pathogens continue to threaten public health worldwide today. Identification of bacterial virulence factors can help to find novel drug/vaccine targets against pathogenicity. It can also help to reveal the mechanisms of the related diseases at the molecular level. With the explosive growth in protein sequences generated in the postgenomic age, it is highly desired to develop computational methods for rapidly and effectively identifying virulence factors according to their sequence information alone. In this study, based on the protein-protein interaction networks from the STRING database, a novel network-based method was proposed for identifying the virulence factors in the proteomes of UPEC 536, UPEC CFT073, P. aeruginosa PAO1, L. pneumophila Philadelphia 1, C. jejuni NCTC 11168 and M. tuberculosis H37Rv. Evaluated on the same benchmark datasets derived from the aforementioned species, the identification accuracies achieved by the network-based method were around 0.9, significantly higher than those by the sequence-based methods such as BLAST, feature selection and VirulentPred. Further analysis showed that the functional associations such as the gene neighborhood and co-occurrence were the primary associations between these virulence factors in the STRING database. The high success rates indicate that the network-based method is quite promising. The novel approach holds high potential for identifying virulence factors in many other various organisms as well because it can be easily extended to identify the virulence factors in many other bacterial species, as long as the relevant significant statistical data are available for them.

Pyrrolidone carboxylic acid (PCA) is formed during a common post-translational modification (PTM) of extracellular and multi-pass membrane proteins. In this study, we developed a new predictor to predict the modification sites of PCA based on maximum relevance minimum redundancy (mRMR) and incremental feature selection (IFS). We incorporated 727 features that belonged to 7 kinds of protein properties to predict the modification sites, including sequence conservation, residual disorder, amino acid factor, secondary structure and solvent accessibility, gain/loss of amino acid during evolution, propensity of amino acid to be conserved at protein-protein interface and protein surface, and deviation of side chain carbon atom number. Among these 727 features, 244 features were selected by mRMR and IFS as the optimized features for the prediction, with which the prediction model achieved a maximum of MCC of 0.7812. Feature analysis showed that all feature types contributed to the modification process. Further site-specific feature analysis showed that the features derived from PCA's surrounding sites contributed more to the determination of PCA sites than other sites. The detailed feature analysis in this paper might provide important clues for understanding the mechanism of the PCA formation and guide relevant experimental validations.

Viral infections result in millions of deaths in the world today. A thorough analysis of virus-host interactomes may reveal insights into viral infection and pathogenic strategies. In this study, we presented a landscape of virus-host interactomes based on protein domain interaction. Compared to the analysis at protein level, this domain-domain interactome provided a unique abstraction of protein-protein interactome. Through comparisons among DNA, RNA, and retrotranscribing viruses, we identified a core of human domains, that viruses used to hijack the cellular machinery and evade the immune system, which might be promising antiviral drug targets. We showed that viruses preferentially interacted with host hub and bottleneck domains, and the degree and betweenness centrality among three categories of viruses are significantly different. Further analysis at functional level highlighted that different viruses perturbed the host cellularmolecular network by common and unique strategies. Most importantly, we creatively proposed a viral disease network among viral domains, human domains and the corresponding diseases, which uncovered several unknown virus-disease relationships that needed further verification. Overall, it is expected that the findings will help to deeply understand the viral infection and contribute to the development of antiviral therapy. [ABSTRACT FROM AUTHOR]