Jacques Ravel and Eric Wommack are co-Editors-in-Chief of the journal Microbiome, which provides a platform for microbiome researchers across environmental, agricultural, and biomedical disciplines to come together and share approaches – an idea that was planted following the 2011 Keystone Symposium on ‘Microbial Communities as Drivers of Ecosystem Complexity’. From microbial surveys and meta-omics approaches, to bioinformatics and community-host interaction modelling, Microbiome brings together the latest research across this growing field. Here Ravel and Wommack explain how this field is developing, the key role collaborative approaches have to play, and the challenges of dealing with ‘big data’.
Why is there a need to bring together the communities of environmental, agricultural and human microbiome researchers?
EW: Most of the approaches that are used in human microbiome research actually got their start in environmental research. We’re talking about at least 15 years ahead of what had been done in the Human Microbiome Project for many of these approaches where you holistically look at entire microbial communities to identify all the players and their particular functions.
Microbiomes are extremely important to the health of the ecosystems. All of the functions that maintain nutrients and carbon balance are all because of the activities of microorganisms. If we extend this idea of microbes providing a healthy system, we can talk about agriculture and of course clinical implications.
JR: We liked the idea of having a platform for the environmental and human medical community to interact and share information, resources, techniques, anything that will benefit both communities. The two communities should be better integrated because they use the same tools, the same ecological principles. There’s been a big shift in the way people approach medicine now, looking at the microbiome not only to cure disease but also to maintain health – I think that’s a big paradigm shift in medicine.
Why is open access coupled with efforts to improve reproducibility so important in this field of research?
EW: It is a young field and things are moving extraordinarily fast with regards to the technology. So much of the science is based on DNA sequencing and there is a new kit on the block among DNA sequencers probably every two years now. With this rapid move in technology, the best practices are moving at light speed. That’s another reason why having disclosure of approaches and methods is needed – all the way from collecting the sample through to analysing the sequence. There can be dozens and dozens of steps in that process, any number of which can influence the outcome. The lack of methodological detail has actually held back advancement in the field at times.
What is collaborative genomics and how does this fit into microbial research?
JR: Genomics is a big term, it means a lot of things, and at the end of the day genomics is a tool. This tool can be applied to so many fields of medicine and environmental sciences. We now have collaborations applying genomics with the nursing school, the dental school, the medical school – we even do things with the law school , studying the regulation of genomic information. Genomics is really becoming the glue that people can be attracted to.
We’ve been describing human microbiomes in many different ways up to ten or 15 years ago, and all of those ways were very broad and biochemical. Now we can go a step further and go into the genes, what the genes are doing, what the products of those genes are, and how and when they function. It’s something that wasn’t possible 20 years ago. Now we can bring all of those analytical tools together and genomics is really the next frontier.
Can you tell us about your research into the microbiome and the role a collaborative approach has to play?
JR: In my group we have projects that are mainly related to women’s health. For example, we study the effect of diet and the microbiome on preterm birth. That collaboration involved the school of nursing; nurses can have a lot of influence on changing the diets of the patient. You generate a lot of data when you enrol pregnant women and follow them all the time, filling out daily questionnaires throughout the pregnancy. That generates a huge dataset. You start to need bioinformaticianse and epidemiologists to sort through all of this data and extract relevant information. Now we have nursing, epidemiology, and OBGYN, and then genomics brings all three disciplines together. We study the microbiome, the human genome, and we follow the changes in the genes expressed in the microbiome and in the women as they go through pregnancy.
EW: My particular field of interest is in viruses, I’m a viral ecologist. It turns out that in most everywhere we’ve looked, viruses outnumber bacteria ten-fold to 6000-fold. We’re talking about astronomical numbers of viruses in natural systems. It turns out there are also astronomical numbers of viruses associated with the human body. Anywhere we find microorganisms, bacteria in particular, we will find viruses. Viruses play an intimate role in the ecology of these organisms – how they grow, how they die, and how they associate with one another. One of the projects Jacques Ravel and I have started, is to bring my expertise in dealing with samples and in analysing communities of viruses, to a question about bacterial vaginosis. It’s an enigmatic disease. There’s not really a single causative organism and so we’ll be looking at the possible role of bacteriophages. It is possible that viruses are infecting the good bacteria in the vagina, causing bad bacteria to take over, which then subsequently causes bacterial vaginosis. It’s a completely open question. We know virtually nothing of the viruses of lactobacillus, which are critical to vaginal health.
How can the scientific community make the most of the large quantities of microbiome data that are now being produced as a result of high throughput technologies?
EW: In genomics there is only one piece of metadata that really matters and that’s the biological taxonomy of the organism. We want to know what organism did this genome belong to. For a microbiome dataset the possibilities are endless as to what this really describes. In addition to rigorous reporting of methods, we want to also have extensive reporting of environmental or clinical metadata so that you can place all of this sequence data into its proper context. The utility of the sequence data increases tremendously when that metadata is more complete. I could say ‘My microbiome sample was from the Chesapeake Bay’ or I could say ‘It’s from the Baltimore inner harbour after a rainstorm in January’. The difference in those kinds of pieces of data is tremendous.
One of the other challenges in this kind of work is that you gather an enormous amount of sequence data and it can take a long time to get through it all. In that period between first gathering the data, analysing and publishing it, it can sometimes be two years or more before you’re actually reaching publication after gathering the data. So we have started a new article type called a ‘microbiome announcement’ that will provide an outlet for scientists to release a dataset with what we call a ‘50,000 foot view’ of what they saw. It’s not heavy on the new findings and the analysis itself, but is more about saying “here’s an interesting dataset, lets provide it to the community, we have things that we’re going to do with it but it could be used for other things too”.
JR: We’ve been trying to start an initiative in systems biology that involves a lot of people. You need mathematicians; that’s the end game, that’s putting all of this data together, modelling it, and finding the gene that doesn’t regulate correctly or the metabolite that’s being made that’s associated with a disease. But you can’t look at that data in individual parts because it’s all correlated, so you need those mathematicians. You also need epidemiologists because you need to understand the metadata. You need bioinformaticians – those people have the capability to generate an environment that allows us to store the data and analyse the data in ways that mathematicians can actually handle it. And of course you need people to generate the data – you need genomicists, people who can do the DNA sequencing, you need pharmacologists who have the tools to generate protein sequences and metabolite spectrums. All of those people need to get together. At the end of the day you get a lot of information and a doctor needs to look at it, to make sense of if in the context of human health. It’s not just ‘one team science’, its ‘big team science’.
More about the Editor(s)
Jacques Ravel is a Professor in microbiology and immunology and Associate Director for Genomics at the Institute for Genome Sciences, at the University of Maryland School of Medicine, USA. He received his PhD in microbial ecology from the University of Maryland at College Park, USA, under the supervision of Russell Hill, before joining the laboratory of Craig Townsend at Johns Hopkins University, USA. Ravel then went on to become an Assistant Investigator at the Institute for Genomic Research, USA. His research involves applying microbial genomics to explore the human microbiome, conduct comparative analyses of microbial genome sequences, and investigate chemical genomics with a focus on developing novel bioinformatics tools for analysing the secondary metabolic potential of microbes.
Eric Wommack is a Professor in the Department of Plant and Soil Sciences at the Delaware Biotechnology Institute, USA. He obtained his PhD in marine estuarine environmental sciences from the University of Maryland, USA. The central goal of his research is to better understand the influence and importance of viral processes within natural ecosystems. Research in the Wommack lab involved field measurements of microbiological processes, quantitative microscopy of viruses within field samples, molecular genetic analysis of viral assemblages, and the assessment of viral diversity through high throughput DNA sequence analysis.