Helen Cook

A system-wide understanding of cellular function requires knowledge of all functional interactions between the expressed proteins. The STRING database aims to collect and integrate this information, by consolidating known and predicted protein-protein association data for a large number of organisms. The associations in STRING include direct (physical) interactions, as well as indirect (functional) interactions, as long as both are specific and biologically meaningful. Apart from collecting and reassessing available experimental data on protein-protein interactions, and importing known pathways and protein complexes from curated databases, interaction predictions are derived from the following sources: (i) systematic co-expression analysis, (ii) detection of shared selective signals across genomes, (iii) automated text-mining of the scientific literature and (iv) computational transfer of interaction knowledge between organisms based on gene orthology. In the latest version 10.5 of STRING, the biggest changes are concerned with data dissemination: the web frontend has been completely redesigned to reduce dependency on outdated browser technologies, and the database can now also be queried from inside the popular Cytoscape software framework. Further improvements include automated background analysis of user inputs for functional enrichments, and streamlined download options. The STRING resource is available online, at http://string-db.org/.

eggNOG is a public database of orthology relationships, gene evolutionary histories and functional annotations. Here, we present version 5.0, featuring a major update of the underlying genome sets, which have been expanded to 4445 representative bacteria and 168 archaea derived from 25 038 genomes, as well as 477 eukaryotic organisms and 2502 viral proteomes that were selected for diversity and filtered by genome quality. In total, 4.4M orthologous groups (OGs) distributed across 379 taxonomic levels were computed together with their associated sequence alignments, phylogenies, HMM models and functional descriptors. Precomputed evolutionary analysis provides fine-grained resolution of duplication/speciation events within each OG. Our benchmarks show that, despite doubling the amount of genomes, the quality of orthology assignments and functional annotations (80% coverage) has persisted without significant changes across this update. Finally, we improved eggNOG online services for fast functional annotation and orthology prediction of custom genomics or metagenomics datasets. All precomputed data are publicly available for downloading or via API queries at http://eggnog.embl.de.

eggNOG is a public resource that provides Orthologous Groups (OGs) of proteins at different taxonomic levels, each with integrated and summarized functional annotations. Developments since the latest public release include changes to the algorithm for creating OGs across taxonomic levels, making nested groups hierarchically consistent. This allows for a better propagation of functional terms across nested OGs and led to the novel annotation of 95 890 previously uncharacterized OGs, increasing overall annotation coverage from 67% to 72%. The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group. Moreover, eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees. We have also incorporated a framework for quickly mapping novel sequences to OGs based on precomputed HMM profiles. Finally, eggNOG version 4.5 incorporates a novel data set spanning 2605 viral OGs, covering 5228 proteins from 352 viral proteomes. All data are accessible for bulk downloading, as a web-service, and through a completely redesigned web interface. The new access points provide faster searches and a number of new browsing and visualization capabilities, facilitating the needs of both experts and less experienced users. eggNOG v4.5 is available at http://eggnog.embl.de.

<ns4:p><ns4:bold>Background: </ns4:bold>The <ns4:italic>w</ns4:italic>Mel strain of<ns4:italic> Wolbachia</ns4:italic> has been successfully introduced into <ns4:italic>Aedes aegypti</ns4:italic> mosquitoes and subsequently shown in laboratory studies to reduce transmission of a range of viruses including dengue, Zika, chikungunya, yellow fever, and Mayaro viruses that cause human disease. Here we report the entomological and epidemiological outcomes of staged deployment of <ns4:italic>Wolbachia</ns4:italic> across nearly all significant dengue transmission risk areas in Australia.</ns4:p><ns4:p> <ns4:bold>Methods: </ns4:bold>The <ns4:italic>w</ns4:italic>Mel strain of <ns4:italic>Wolbachia</ns4:italic> was backcrossed into the local <ns4:italic>Aedes aegypti</ns4:italic> genotype (Cairns and Townsville backgrounds) and mosquitoes were released in the field by staff or via community assisted methods. Mosquito monitoring was undertaken and mosquitoes were screened for the presence of <ns4:italic>Wolbachia</ns4:italic>. Dengue case notifications were used to track dengue incidence in each location before and after releases.</ns4:p><ns4:p> <ns4:bold>Results: </ns4:bold>Empirical analyses of the <ns4:italic>Wolbachia</ns4:italic> mosquito releases, including data on the density, frequency and duration of <ns4:italic>Wolbachia</ns4:italic> mosquito releases, indicate that <ns4:italic>Wolbachia</ns4:italic> can be readily established in local mosquito populations, using a variety of deployment options and over short release durations (mean release period 11 weeks, range 2-22 weeks). Importantly, <ns4:italic>Wolbachia</ns4:italic> frequencies have remained stable in mosquito populations since releases for up to 8 years. Analysis of dengue case notifications data demonstrates near-elimination of local dengue transmission for the past five years in locations where <ns4:italic>Wolbachia</ns4:italic> has been established. The regression model estimate of <ns4:italic>Wolbachia </ns4:italic>intervention effect from interrupted time series analyses of case notifications data prior to and after releases, indicated a 96% reduction in dengue incidence in <ns4:italic>Wolbachia </ns4:italic>treated populations (95% confidence interval: 84 – 99%).</ns4:p><ns4:p> <ns4:bold>Conclusion: </ns4:bold>Deployment of the <ns4:italic>w</ns4:italic>Mel strain of <ns4:italic>Wolbachia</ns4:italic> into local <ns4:italic>Ae. aegypti</ns4:italic> populations across the Australian regional cities of Cairns and most smaller regional communities with a past history of dengue has resulted in the reduction of local dengue transmission across all deployment areas.</ns4:p>