Knowledge of viruses revealed by new metagenomics technologies

Metagenomic sequencing techniques allow the study of microbiomes from a wide variety of habitats, and using this to study phages (the genomes of bacteriophages integrated into a circular bacterial chromosome) has expanded knowledge about viruses that integrate into bacterial genomes and how they benefit their hosts.

Ph.D. Flinders University PhD candidate Laura Inglis — part of the Flinders Accelerator for Microbiome Exploration (FAME), an interdisciplinary research group at Flinders University’s College of Science and Engineering — outlined the benefits in her newly published research on transforming phages.

Laura Inglis and Robert Edwards’ paper “How metagenomics has changed our understanding of bacteriophages in microbiome research” was published in the journal Microorganisms.

” the microbiome is an integral part of most ecosystems, but it has been particularly challenging to study microbiomes from very different habitats,” says Ms Inglis. “Metagenomic sequencing is changing that. This is particularly useful for searching phages from different environmental conditions, but many genomes are added to databases without including complete metadata.

“Being able to automatically sort these sequences into an environmental ontology would make these sequences useful in future projects, but we need much more high quality data to determine how best to sort these sequences.”

Increasing the number of sequences uploaded to online databases has both pros and cons. This means that more data is available for use, but processing such a huge amount of data becomes unmanageable.

“There are a lot of problems with curating metagenomes, but using machine learning for automatic curation could alleviate some of those problems,” explains Ms Inglis.

Phages play a significant role in the microbiomes of many species and in the different environments. They can protect their host from deadly infections and give their host access to useful genes, such as antimicrobial resistance or toxin production, but how phages interact with their host varies depending on the environment.

“Several factors influence whether bacteriophages will choose lysis or lysogenesis, and several different hypotheses attempt to explain why some environments have higher rates of lysis or lysogenesis,” says Ms Inglis.

Many studies have examined phages in a variety of environments and conditions, but only looked at a few different environments or conditions at a time. Ms Inglis says that taking advantage of the large number of online metagenomes could allow for a wider study of the rates of lysis and lysogenesis in different environments at the same time, but she admits that genome curation issues need to be resolved first.

Researchers have conducted many studies on phages from different environments and have developed hypotheses about what factors influence survival strategies such as the lytic/lysogenic solution, although much remains to be learned about how prophages interact with their hosts in different environments.

“More information about metagenomes and prophages could provide many insights into human and environmental healthand gaining a better understanding of what a healthy microbiome should look like could allow us to more quickly and accurately identify changes in microbiomes that may be indicative of disease,” says Ms Inglis.

One problem with using open-access metagenomic data is that sequences added to databases often have little to no metadata to work with, so finding enough sequences can be difficult. Many metagenomes have been curated by hand, but this is a time-consuming process and relies heavily on the uploader being accurate and thorough in filling in the metadata fields, and the curators working with the same ontologies.

Using algorithms to automatically sort metagenomes based on a taxonomic or functional profile can be an effective solution to the problem of manually curated metagenomes, but this requires that the algorithm be trained on carefully trained datasets and use the most informative profile in order to minimize errors.

Ms Inglis’s paper on the gut microbiome is one of seven recent papers by Flinders University’s FAME lab, where the multidisciplinary research team provides access to microbiome and metagenomics resources that help accelerate microbiome research.

Other notable recent publications from the FAME lab include Vijini Malavaarachchi’s research on a new bioinformatics tool for genome assembly from multi-bacterial genome data; Ph.D. student Lias’ research on microbial functions in coral health (with graduate student Bhavya Papudeshi) and her review of the ecophysiology of one coral species in contemporary Caribbean coral reef environments; and PhD student Susie Grigson on how to use advanced mathematics and computer science with biology to help understand microbes and what they do.

The FAME lab was founded by Robert Edwards, Matthew Flinders Research Fellow in Bioinformatics, who coordinates computational analysis of microbiome-related DNA sequences, along with Elizabeth Dinsdale, Matthew Flinders Research Fellow in Marine Biology, whose research uses genomics to study microbial biodiversity and ecology. and viruses on coral reefs, kelp forests, and shark epidermis.