[Show abstract][Hide abstract] ABSTRACT: The Bacillus phage phiAGATE is a novel myovirus isolated from the waters of Lake Góreckie (a eutrophic lake in western Poland). The bacteriophage infects Bacillus pumilus, a bacterium commonly observed in the mentioned reservoir. Analysis of the phiAGATE genome (149844 base pairs) resulted in 204 predicted protein-coding sequences (CDSs), of which 53 could be functionally annotated. Further investigation revealed that the bacteriophage is a member of a previously undescribed cluster of phages (for the purposes of this study we refer to it as "Bastille group") within the Spounavirinae subfamily. Here we demonstrate that these viruses constitute a distinct branch of the Spounavirinae phylogenetic tree, with limited similarity to phages from the Twortlikevirus and Spounalikevirus genera. The classification of phages from the Bastille group into any currently accepted genus proved extremely difficult, prompting concerns about the validity of the present taxonomic arrangement of the subfamily.
PLoS ONE 01/2014; 9(1):e86632. DOI:10.1371/journal.pone.0086632 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new paradigm of biological investigation takes advantage of technologies that produce large high throughput datasets, including genome sequences, interactions of proteins, and gene expression. The ability of biologists to analyze and interpret such data relies on functional annotation of the included proteins, but even in highly characterized organisms many proteins can lack the functional evidence necessary to infer their biological relevance.
Here we have applied high confidence function predictions from our automated prediction system, PFP, to three genome sequences, Escherichia coli, Saccharomyces cerevisiae, and Plasmodium falciparum (malaria). The number of annotated genes is increased by PFP to over 90% for all of the genomes. Using the large coverage of the function annotation, we introduced the functional similarity networks which represent the functional space of the proteomes. Four different functional similarity networks are constructed for each proteome, one each by considering similarity in a single Gene Ontology (GO) category, i.e. Biological Process, Cellular Component, and Molecular Function, and another one by considering overall similarity with the funSim score. The functional similarity networks are shown to have higher modularity than the protein-protein interaction network. Moreover, the funSim score network is distinct from the single GO-score networks by showing a higher clustering degree exponent value and thus has a higher tendency to be hierarchical. In addition, examining function assignments to the protein-protein interaction network and local regions of genomes has identified numerous cases where subnetworks or local regions have functionally coherent proteins. These results will help interpreting interactions of proteins and gene orders in a genome. Several examples of both analyses are highlighted.
The analyses demonstrate that applying high confidence predictions from PFP can have a significant impact on a researchers' ability to interpret the immense biological data that are being generated today. The newly introduced functional similarity networks of the three organisms show different network properties as compared with the protein-protein interaction networks.
[Show abstract][Hide abstract] ABSTRACT: Malaria parasites undergo a population expansion inside the host liver before disease onset. Developmental arrest inside host hepatocytes elicits protective immune responses. Therefore, elucidation of the molecular mechanisms leading to mature hepatic merozoites, which initiate the pathogenic blood phase, also informs anti-malaria vaccine strategies. Using targeted gene deletion in the rodent model malaria parasite Plasmodium berghei, we show that a Plasmodium-specific Apicoplast protein plays an important role for Liver Merozoite formation (PALM). While the resulting knockout mutants develop normally for most of the life cycle, merozoite release into the blood stream and the ability to establish an infection are severely impaired. Presence of a signature blood-stage antigen, merozoite surface protein 1 and normal apicoplast morphology indicate that the inability to finalize merozoite segregation is a direct consequence of loss of PALM function. Experimental immunization of mice with as few as two doses of palm(-) sporozoites can elicit sterile protection up to 110 days after final immunization. Our data establish that a tailor-made arrest in the final steps of hepatic merozoite formation can induce strong protective immune responses and that malaria parasites employ a distinct apicoplast protein for efficient formation of pre-erythrocytic merozoites.
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