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1. Automated classification of giant virus genomes using a random forest model built on trademark protein families

   https://doi.org/10.1038/s44298-024-00021-9  

   Ha, Anh D. ; Aylward, Frank O. ( March 2024 , npj Viruses)

   Viruses of the phylumNucleocytoviricota, often referred to as “giant viruses,” are prevalent in various environments around the globe and play significant roles in shaping eukaryotic diversity and activities in global ecosystems. Given the extensive phylogenetic diversity within this viral group and the highly complex composition of their genomes, taxonomic classification of giant viruses, particularly incomplete metagenome-assembled genomes (MAGs) can present a considerable challenge. Here we developed TIGTOG (TaxonomicInformation ofGiant viruses usingTrademarkOrthologousGroups), a machine learning-based approach to predict the taxonomic classification of novel giant virus MAGs based on profiles of protein family content. We applied a random forest algorithm to a training set of 1531 quality-checked, phylogenetically diverseNucleocytoviricotagenomes using pre-selected sets of giant virus orthologous groups (GVOGs). The classification models were predictive of viral taxonomic assignments with a cross-validation accuracy of 99.6% at the order level and 97.3% at the family level. We found that no individual GVOGs or genome features significantly influenced the algorithm’s performance or the models’ predictions, indicating that classification predictions were based on a comprehensive genomic signature, which reduced the necessity of a fixed set of marker genes for taxonomic assigning purposes. Our classification models were validated with an independent test set of 823 giant virus genomes with varied genomic completeness and taxonomy and demonstrated an accuracy of 98.6% and 95.9% at the order and family level, respectively. Our results indicate that protein family profiles can be used to accurately classify large DNA viruses at different taxonomic levels and provide a fast and accurate method for the classification of giant viruses. This approach could easily be adapted to other viral groups.

    

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2. High Transcriptional Activity and Diverse Functional Repertoires of Hundreds of Giant Viruses in a Coastal Marine System

   https://doi.org/10.1128/mSystems.00293-21  

   Ha, Anh D. ; Moniruzzaman, Mohammad ; Aylward, Frank O. ; Etten, James Van ( January 2021 , mSystems)

   Bordenstein, Seth (Ed.)

   ABSTRACT Viruses belonging to the Nucleocytoviricota phylum are globally distributed and include members with notably large genomes and complex functional repertoires. Recent studies have shown that these viruses are particularly diverse and abundant in marine systems, but the magnitude of actively replicating Nucleocytoviricota present in ocean habitats remains unclear. In this study, we compiled a curated database of 2,431 Nucleocytoviricota genomes and used it to examine the gene expression of these viruses in a 2.5-day metatranscriptomic time-series from surface waters of the California Current. We identified 145 viral genomes with high levels of gene expression, including 90 Imitervirales and 49 Algavirales viruses. In addition to recovering high expression of core genes involved in information processing that are commonly expressed during viral infection, we also identified transcripts of diverse viral metabolic genes from pathways such as glycolysis, the TCA cycle, and the pentose phosphate pathway, suggesting that virus-mediated reprogramming of central carbon metabolism is common in oceanic surface waters. Surprisingly, we also identified viral transcripts with homology to actin, myosin, and kinesin domains, suggesting that viruses may use these gene products to manipulate host cytoskeletal dynamics during infection. We performed phylogenetic analysis on the virus-encoded myosin and kinesin proteins, which demonstrated that most belong to deep-branching viral clades, but that others appear to have been acquired from eukaryotes more recently. Our results highlight a remarkable diversity of active Nucleocytoviricota in a coastal marine system and underscore the complex functional repertoires expressed by these viruses during infection. IMPORTANCE The discovery of giant viruses has transformed our understanding of viral complexity. Although viruses have traditionally been viewed as filterable infectious agents that lack metabolism, giant viruses can reach sizes rivalling cellular lineages and possess genomes encoding central metabolic processes. Recent studies have shown that giant viruses are widespread in aquatic systems, but the activity of these viruses and the extent to which they reprogram host physiology in situ remains unclear. Here, we show that numerous giant viruses consistently express central metabolic enzymes in a coastal marine system, including components of glycolysis, the TCA cycle, and other pathways involved in nutrient homeostasis. Moreover, we found expression of several viral-encoded actin, myosin, and kinesin genes, indicating viral manipulation of the host cytoskeleton during infection. Our study reveals a high activity of giant viruses in a coastal marine system and indicates they are a diverse and underappreciated component of microbial diversity in the ocean. 

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3. Genomes of the dinoflagellate Polarella glacialis encode tandemly repeated single exon genes with adaptive functions

   https://doi.org/10.1186/s12915-020-00782-8  

   Stephens, T. G. ; González-Pech, R. A. ; Cheng, Y. ; Mohamed, A. R. ; Burt, D. W. ; Bhattacharya, D. ; Ragan, M. A. ; Chan, C. X. ( January 2020 , BMC biology)

   Background: Dinoflagellates are taxonomically diverse and ecologically important phytoplankton that are ubiquitously present in marine and freshwater environments. Mostly photosynthetic, dinoflagellates provide the basis of aquatic primary production; most taxa are free-living, while some can form symbiotic and parasitic associations with other organisms. However, knowledge of the molecular mechanisms that underpin the adaptation of these organisms to diverse ecological niches is limited by the scarce availability of genomic data, partly due to their large genome sizes estimated up to 250 Gbp. Currently available dinoflagellate genome data are restricted to Symbiodiniaceae (particularly symbionts of reef-building corals) and parasitic lineages, from taxa that have smaller genome size ranges, while genomic information from more diverse free living species is still lacking. Results: Here, we present two draft diploid genome assemblies of the free-living dinoflagellate Polarella glacialis, isolated from the Arctic and Antarctica. We found that about 68% of the genomes are composed of repetitive sequence, with long terminal repeats likely contributing to intra-species structural divergence and distinct genome sizes (3.0 and 2.7 Gbp). For each genome, guided using full-length transcriptome data, we predicted > 50,000 high-quality protein-coding genes, of which ~40% are in unidirectional gene clusters and ~25% comprise single exons. Multi-genome comparison unveiled genes specific to P. glacialis and a common, putatively bacterial origin of ice-binding domains in cold-adapted dinoflagellates. Conclusions: Our results elucidate how selection acts within the context of a complex genome structure to facilitate local adaptation. Because most dinoflagellate genes are constitutively expressed, Polarella glacialis has enhanced transcriptional responses via unidirectional, tandem duplication of single-exon genes that encode functions critical to survival in cold, low-light polar environments. These genomes provide a foundational reference for future research on dinoflagellate evolution. 

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4. ViralRecall—A Flexible Command-Line Tool for the Detection of Giant Virus Signatures in ‘Omic Data

   https://doi.org/10.3390/v13020150  

   Aylward, Frank O. ; Moniruzzaman, Mohammad ( February 2021 , Viruses)

   null (Ed.)

   Giant viruses are widespread in the biosphere and play important roles in biogeochemical cycling and host genome evolution. Also known as nucleo-cytoplasmic large DNA viruses (NCLDVs), these eukaryotic viruses harbor the largest and most complex viral genomes known. Studies have shown that NCLDVs are frequently abundant in metagenomic datasets, and that sequences derived from these viruses can also be found endogenized in diverse eukaryotic genomes. The accurate detection of sequences derived from NCLDVs is therefore of great importance, but this task is challenging owing to both the high level of sequence divergence between NCLDV families and the extraordinarily high diversity of genes encoded in their genomes, including some encoding for metabolic or translation-related functions that are typically found only in cellular lineages. Here, we present ViralRecall, a bioinformatic tool for the identification of NCLDV signatures in ‘omic data. This tool leverages a library of giant virus orthologous groups (GVOGs) to identify sequences that bear signatures of NCLDVs. We demonstrate that this tool can effectively identify NCLDV sequences with high sensitivity and specificity. Moreover, we show that it can be useful both for removing contaminating sequences in metagenome-assembled viral genomes as well as the identification of eukaryotic genomic loci that derived from NCLDV. ViralRecall is written in Python 3.5 and is freely available on GitHub: https://github.com/faylward/viralrecall. 

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5. Infection strategy and biogeography distinguish cosmopolitan groups of marine jumbo bacteriophages

   https://doi.org/10.1038/s41396-022-01214-x  

   Weinheimer, Alaina R. ; Aylward, Frank O. ( June 2022 , The ISME Journal)

   Abstract Recent research has underscored the immense diversity and key biogeochemical roles of large DNA viruses in the ocean. Although they are important constituents of marine ecosystems, it is sometimes difficult to detect these viruses due to their large size and complex genomes. This is true for “jumbo” bacteriophages, which have genome sizes >200 kbp and large capsids reaching up to 0.45 µm in diameter. In this study, we sought to assess the genomic diversity and distribution of these bacteriophages in the ocean by generating and analyzing jumbo phage genomes from metagenomes. We recover 85 marine jumbo phages that ranged in size from 201 to 498 kilobases, and we examine their genetic similarities and biogeography together with a reference database of marine jumbo phage genomes. By analyzing Tara Oceans metagenomic data, we show that although most jumbo phages can be detected in a range of different size fractions, 17 of our bins tend to be found in those greater than 0.22 µm, potentially due to their large size. Our network-based analysis of gene-sharing patterns reveals that jumbo bacteriophages belong to five genome clusters that are typified by diverse replication strategies, genomic repertoires, and potential host ranges. Our analysis of jumbo phage distributions in the ocean reveals that depth is a major factor shaping their biogeography, with some phage genome clusters occurring preferentially in either surface or mesopelagic waters, respectively. Taken together, our findings indicate that jumbo phages are widespread community members in the ocean with complex genomic repertoires and ecological impacts that warrant further targeted investigation. 

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