A few notes from the Applied Hologenomics Conference 2024

I’m just back from the Applied Hologenomics Conference in 2024 (See also #AHC2024 on Twitter ) in Copenhagen and thought to reflect a little on the conference and highlight the bits that particularly stuck with me.

The first thing I want to say is that a paradigm shift is happening here.

I think what is happening here is a step away from the reductionist view of the past that goes beyond the systems biology approach that has been establishing itself during the last 10-20 years.

While systems biology has been an enormously important step up from the reductionist view of the past by highlighting the fact that the whole is more than the sum of its parts, is typically focused on one organism at a time.

Hologenomics additionally embraces the fact that no organism is living in complete isolation but rather in a very tight interplay with a multitude of microorganisms, which have a tremendously important influence, of which we have only perhaps started to learn about.

Something that highlights this is the fact - as pointed out by Seth Bordenstein in the closing keynote - that close to 50% of diabetes and a few other diseases have a direct causal link to the microbiome of the host.

Seth in his keynote says we are in a third biological epoch (after The origin of species and the Modern Synthesis), where he went as far as saying “centrality of microbes in biology is far more accurate vision of nature”.

While I’m personally not completely sold on that, I guess I see the point. In my view though I think the most important thing is to realize that we are dealing with a “system of systems”, rather than just the single systems of individual organisms. Systems-of-systems is also a well-established engineering discipline which means there might be opportunities for very important insights by letting these fields cross-pollinate.

That about the general theme going on here.

Let me then share my very incomplete and randomly selected set of tidbits, facts and remarks that I found was particularly interesting new points of insight for my specific interests.

I need to add the additional caveat though that I’m not a microbiologist by training but rather come from a very computationally oriented background and so do have my own strong biases. There were such a wealth of interesting material and insights presented here that I can not truly make justice for, simply because I might not know the field enough to be able to process it in real time. Thus, the list is by necessity a very personal and biased one. But sharing it nonetheless:

• Søren Sørensen mentioned that it is a general challenge to link the plasmids bacteria carry, to their host bacteria.
• There were companies present that have developed solutions for this though, including Phase Genomics
• Søren also outlined that Bacteroidetes, Escherichia and Klebsiella are the dominant bacterial hosts for plasmids, where the Bacteroidetes phylum in particular has very high mobility of plasmids.
• I also talked to representatives Clinical Microbiomics has a platform for studying microbiomes. It seems to be a little more focused on research than routine diagnostics though.
• Rachel Carmody from Harvard University had a pretty fascinating talk sharing how people in the industrialized world absorb food mostly in the small intestine, while in the non-industrial world mostly in the colon, because of the differences in fiber content (more in the non-industrial world).
• Aviaja Hauptmann from University of Greenland had a very thought-provoking talk as well, highlighting how the microbiomes of the indigenous people of Greenland has adapted well to the almost exclusively meat-based diet. She mentioned the challenges arising today though, when 80% of food is imported more western style food, whieh has lead to an explosion in non-communicable diseases. They now have up toward 10% diabetes.
• Ivan Liachko from Phase Genomics presented about their method for linking phages, plasmids and antimicrobial resistance genes to hosts. They use formalin to cross-link sequences close to each other before bacterial cells are lysed, and then create junctions between those sequences, so that spatially closely located sequences will be “glued” together, and appear together in sequenced reads.
• They also say they built the world’s largest phage/bacteria database.
• Ivan shared interesting insights about how we can get some of the benefits of phages without their potential drawbacks, by using lysins, which are proteins made by the phages, that typically work around anti-microbial resistance.
• Lone Gram from Technical University of Denmark presented some thought-provoking facts including the huge important of microalgae (in the oceans), as they produce more than 50% of the oxygen we have in the athmosphere. She also mentioned that Roseobacter are the most dominant bacteria of the oceans / marine microbiota.
• In the panel discussion there were mostly a lot of discussion about funding. Lone mentioned a thought-worthy thing though, as she reflected that we need to get [back] into the proper scientific loop, producing the data needed for the question at hand (and perhaps not huge amounts more), not just descriptive science of huge data sets. I think this is a topic for a whole separate post, if not series of posts.
• Katerina Guschanski from University of Edinburgh had a fantastic talk and concluded that figuring out how much humans affected the antimicrobial world requires a temporal approach, since the antimicrobials already existed in nature). She went on to describe how they found out that Dental calculus is a great way to study microbiota of ancient organisms, as this is something you can find in pretty much any museum animal, and it will be protective enough to contain a lot of preserved microbiomal DNA. E.g. they have studied the microbiomes of brown bears in Sweden as the population was almost put to extinction, and back again, where they saw how oral diseases were significantly more prevalent in the bears during the bottleneck.
• Antton Alberdi from University of Copenhagen shared about many interesting things, including the Earth HoloGenome Initiative.
• Benjamin Auch from Phase Genomics had an interesting talk and shared a few interesting remarks, including the fact that we are often ignoring the phages that also come along when we transplant faeces, and also that faecal transplants do not eliminate anti-microbial resistance.
• Bryan Wang from University of Copenhagen had a fascinating talk showing how they were able to study the spatial distribution of bacteria using a clever new technique, and could show how there is a large spatial factor in how different bacteria aggregate. That is different species tend to aggregate in different fashion.
• In the end, Seth Bordenstein, Director at the Penn State University Microbiome Center, as mentioned, had a really though-provoking talk and concluded that there is a huge shift in our understanding of biology that is happening now, but how this is not yet reflected in textbooks. For example the standard biology text-book (Campbell), does mention microbes in a separate chapter, rather than including it together with the other content, and not having the holobiont view. To underscore this he mentioned how some studies show the microbiome contributes close to 50% to HDL Cholesterol, BMI and [diabetes?] (Rotschild, 2018 Nature). I haven’t been able to verify this claim yet (perhaps found the wrong paper?) but will see if I can find it later.

Hope this gives some slight glimpses of all the good stuff being presented here. If this is not enough, the recordings of the talks should start getting published online in the next week.

Overall, I had a great time at the conference. The only thing I realized was that the focus of the talks were both less focused on clinically relevant topics and much more biology-oriented rather than computationally oriented than I was perhaps expecting. This is still OK, but it means it will take some more mental work for me to translate these insights into what it might mean in my immediate context as a rather computationally oriented bioinformatician in clinical microbiology.

Overall, I’m thankful to the organizers for an inspiring conference where I learned a lot, and got an updated view of the holobiont!