Supplementary data are available at Bioinformatics online.

Environmental genomics can describe all forms of organisms—cellular and viral—present in a community. The analysis of such eco-systems biology data relies heavily on reference databases, e.g., taxonomy or gene function databases. Reference databases of symbiosis sensu lato, although essential for the analysis of organism interaction networks, are lacking. By mining existing databases and literature, we here provide a comprehensive and manually curated database of taxonomic links between viruses and their cellular hosts.

Viruses are diverse and play significant ecological roles in marine ecosystems. However, our knowledge of genome-level diversity in viruses is biased toward those isolated from few culturable hosts. Here, we determined 1,352 nonredundant complete viral genomes from marine environments. Lifting the uncertainty that clouds short incomplete sequences, whole-genome-wide analysis suggests that these environmental genomes represent hundreds of putative novel viral genera. Predicted hosts include dominant groups of marine bacteria and archaea with no isolated viruses to date. Some of the viral genomes encode many functionally related enzymes, suggesting a strong selection pressure on these marine viruses to control cellular metabolisms by accumulating genes.

Motivation: Unexpected drug activities derived from off-targets are usually undesired and harmful; however, they can occasionally be beneficial for different therapeutic indications. There are many uncharacterized drugs whose target proteins (including the primary target and off-targets) remain unknown. The identification of all potential drug targets has become an important issue in drug repositioning to reuse known drugs for new therapeutic indications.Results: We defined pharmacological similarity for all possible drugs using the US Food and Drug Administration's (FDA's) adverse event reporting system (AERS) and developed a new method to predict unknown drug–target interactions on a large scale from the integration of pharmacological similarity of drugs and genomic sequence similarity of target proteins in the framework of a pharmacogenomic approach. The proposed method was applicable to a large number of drugs and it was useful especially for predicting unknown drug–target interactions that could not be expected from drug chemical structures. We made a comprehensive prediction for potential off-targets of 1874 drugs with known targets and potential target profiles of 2519 drugs without known targets, which suggests many potential drug–target interactions that were not predicted by previous chemogenomic or pharmacogenomic approaches.Availability: Softwares are available upon request.Contact: yamanishi@bioreg.kyushu-u.ac.jpSupplementary Information: Datasets and all results are available at http://cbio.ensmp.fr/~yyamanishi/aers/.

Viruses infecting microorganisms are ubiquitous and abundant in the ocean. However, it is unclear when and where the numerous viral particles we observe in the sea are produced and whether they are active. To address these questions, we performed time-series analyses of viral metagenomes and microbial metatranscriptomes collected over a period of 24 h at a Japanese coastal site. Through mapping the metatranscriptomic reads on three sets of viral genomes ((i) 878 contigs of Osaka Bay viromes (OBV), (ii) 1766 environmental viral genomes from marine viromes, and (iii) 2429 reference viral genomes), we revealed that all the local OBV contigs were transcribed in the host fraction. This indicates that the majority of viral populations detected in viromes are active, and suggests that virions are rapidly diluted as a result of diffusion, currents, and mixing. Our data further revealed a peak of cyanophage gene expression in the afternoon/dusk followed by an increase of genomes from their virions at night and less-coherent infectious patterns for viruses putatively infecting various groups of heterotrophs. This suggests that cyanophages drive the diel release of cyanobacteria-derived organic matter into the environment and viruses of heterotrophic bacteria might have adapted to the population-specific life cycles of hosts.

Jumbo phages infecting Ralstonia solanacearum were isolated in Thailand (ϕRSL2) and Japan (ϕRSF1). They were similar regarding virion morphology, genomic arrangement, and host range. Phylogenetic and proteomic tree analyses demonstrate that the ϕRSL2 and ϕRSF1 belong to a group of evolutionary related phages, including Pseudomonas phages ϕKZ, 201ϕ2-1 and all previously described ϕKZ-related phages. Despite conserved genomic co-linearity between the ϕRSL2 and ϕRSF1, they differ in protein separation patterns. A major difference was seen in the detection of virion-associated-RNA polymerase subunits. All β- and β'-subunits were detected in ϕRSF1, but one β'-subunit was undetected in ϕRSL2. Furthermore, ϕRSF1 infected host cells faster (latent period: 60 and 150min for ϕRSF1 and ϕRSL2, respectively) and more efficiently than ϕRSL2. Therefore, the difference in virion-associated-RNA polymerase may affect infection efficiency. Finally, we show that ϕRSF1 is able to inhibit bacterial wilt progression in tomato plants.

The use of metagenomics has dramatically expanded the known virosphere, but freshwater viral diversity and the ecological relationships between viruses and hosts remain poorly understood. In this study, we conducted a large-scale metagenomic exploration of planktonic dsDNA prokaryotic viruses by sequencing both virion (<0.22 μm) and cellular (0.22-5.0 μm) fractions collected spatiotemporally from a deep freshwater lake (Lake Biwa, Japan). This simultaneously reconstructed 183 complete (i.e., circular) viral genomes and 57 bacterioplankton metagenome-assembled genomes. Spatiotemporal, intra-and extra-cellular dynamics of individual viruses assessed through metagenomic read coverage revealed a hypolimnion-specific viral community analogous to the vertically-stratified bacterioplankton community. The hypolimnetic community was generally stable during stratification, but occasionally shifted abruptly due to lysogenic induction, presumably reflecting low bacterial productivity in the hypolimnion. Genes involved in assimilatory sulfate reduction were encoded in 20 (10.9%) viral genomes, including those of dominant viruses, and may aid viral propagation in sulfurlimited freshwater systems. Hosts were predicted for 40 (21.9%) viral genomes, encompassing 10 phyla (or classes of Proteobacteria) including ubiquitous freshwater bacterioplankton lineages (e.g., LD12 and Ca. Nitrosoarchaeum). Comparison with published metagenomes revealed phylogeographic connectivity of viral communities in geographically isolated habitats, probably following the phylogeographic connectivity of their hosts. Notably, analogous to their hosts, actinobacterial viruses were among the most diverse, ubiquitous, and abundant viral groups in freshwater systems, with high lytic replication rates in surface waters. This result suggested that freshwater Actinobacteria are under high viral lytic pressure, which likely facilitated their genomic micro-diversification to elude viral recognition. Significance StatementMetagenomics allows for the reconstruction of bacterial and viral genomes without cultivation, contributing substantially to elucidation of bacterial and viral diversity and their key ecological roles.In this study, we report the largest-scale metagenomic exploration of freshwater prokaryotic viruses to date. We investigated the hypolimnion of a deep freshwater lake and tracked viruses throughout their life cycles, including both intra-and extra-cellular phases. This method allowed us to reconstruct both viral and host genomes and characterize numerous novel virus-host interactions, including those involving ubiquitous freshwater bacterial lineages. When the data were compared with published metagenomic datasets, we uncovered genome-resolved phylogeographic connectivity among viruses from geographically isolated habitats and identified ecologically important viral groups that are ubiquitous in aquatic habitats.In total, 12 water samples were collected at a pelagic site on Lake Biwa, the largest freshwater lake in Japan. The epilimnion (5 m) was ...

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