Conversations with experts: decoding the future of sequencing
January 22, 2025
The 6th edition of the Revolutionizing Next-Generation Sequencing (RNGS) conference brings together experts in genomics and sequencing to explore the latest advances. We talked with two VIB researchers and Organizing Committee members, Bram Van den Bergh (postdoc in the Michiels Lab at the Center for Microbiology) and Wouter De Coster (postdoc in the Rademakers Lab at the Center for Molecular Neurology), about their work, the fast-moving field of sequencing, and their motivations.
Hi both, could you explain the work you do and how sequencing ties into it?
Bram: At the VIB-KU Leuven Center for Microbiology, I study the evolution of antibiotic tolerance. In contrast to antibiotic resistance, this is how bacteria can survive antibiotics without growing. Our lab was one of the first to study this broader perspective, and that led me to sequencing—we needed it to track DNA sequence changes during evolution. Over time, I’ve shifted more toward the technological side of things, which is why I’m now helping to organize the RNGS conference. In February, I’ll start a new role at VIB Tech Watch, where I’ll test and evaluate new technologies.
Wouter: My focus at the VIB-UAntwerp Center for Molecular Neurology is on long-read sequencing to identify genetic factors in frontotemporal dementia (FTD). Long-read sequencing provides insights, mainly for structural variation and repeat expansions, that are invisible with other technologies. I started with nanopore sequencing during my PhD and it’s grown into a major focus. Sequencing technology is really something I’m thinking about day and night!
What exciting research projects are you currently working on?
Bram: In my research, we discovered that antibiotic tolerance evolves so quickly due to single-nucleotide DNA changes that drastically boost survival rates. These changes clustered in certain genes, so we deleted these and ran the experiment again. Subsequently, we saw new targets appear, regulatory mutations increase, and larger DNA duplications. It’s like a real-life "life finds a way" moment. I’m now wrapping up tests to confirm these results in natural strains.
Wouter: I’m working on characterizing a repeat expansion linked to a type of FTD in a tricky DNA region that only long-read sequencing could analyze. We found the same expansion in 60% of patients with this subtype worldwide. We’re now studying differences in these repeats to see what they mean. Thanks to new tools, we’re seeing things with clarity like never before.
This is the 6th edition of the RNGS conference and the sequencing field has evolved massively since. What new trends or advances do you expect to be highlighted in this edition?
Wouter: Protein sequencing is a big topic right now. There’s a lot of potential to directly identify peptides instead of relying on mass spectrometry. There’s a lot of hype, but I haven’t seen companies fully convince me yet. I’m most interested to see technologies presented at the conference that have moved beyond proof-of-concept phase to answer real scientific questions.
Bram: Indeed, it would be amazing if protein sequencing could reach the level of precision we’ve achieved with DNA sequencing, but it’s a much tougher challenge. I’m particularly excited to see combinations of different single-cell omics techniques, like sequencing the transcriptome and metabolome from a single sample. That’s exciting!
Are there specific sessions or talks you’re looking forward to?
Bram: I’m especially eager to see Gang Fang’s talk on the bacterial epigenome. His work wasn’t on my radar until I researched speakers for the conference, but it aligns closely with our work. I’m curious to see if there are opportunities for collaboration.
Wouter: I’m looking forward to Alexander Hoischen’s talk on using long-read sequencing in rare disease research. Some patients face long diagnostic journeys, but now a single long-read sequencing assay can provide answers. That, along with updates on protein sequencing, will be highlights for me.
What societal impact do you expect from sequencing in the next decade?
Bram: Faster diagnostics. For example, diagnosing tuberculosis and selecting the right antibiotics currently takes time. A sequencing-based approach could make this faster and more accurate.
Wouter: Indeed, preventive genome sequencing is the next frontier. By understanding a patient’s genome, we could tailor therapies or lifestyle changes, and as such potentially prevent rather than treat diseases.
I can imagine ethical questions arise with this. Do you ever think about that?
Wouter: Ethical questions do come with this. How much should we reveal? For instance, a variant that only slightly increases Alzheimer’s risk might not need to be disclosed. These discussions will involve patients, doctors, and society as a whole.
Bram: I agree, and there’s another layer to this. What if insurers or governments misuse genomic data? This isn’t a problem for biotech alone but also for IT and data security. These are societal issues that require public debate and solutions. As academics, we can inform the discussion, but the final decisions need to come from society-at-large.
Wouter: Yes, but I think sequencing should not be all that different from the blood tests we do today. These questions also shouldn’t stand in the way of technological progress. An analogy is the invention of the car—we didn’t stop developing it just because some people might drive drunk. Most technologies are inherently good, and we shouldn’t avoid creating them due to potential risks. It’s about finding the right balance between innovation and responsibility.
Bram: It’s an important discussion that we even discussed at past conferences. Yves Moreau from KU Leuven gave a fascinating talk about ethical dilemmas, raising some of these very issues.
What actually motivates you to work in this field?
Bram: The thrill of a new tool on the bench or hearing a talk and thinking, “I wish I’d thought of that.” It’s very exciting to bring smart, creative people together to make breakthroughs.
Wouter: My work focuses on a devastating disease and heartbreaking patient stories. Knowing that the methods we’re developing can now achieve in hours what once took decades is very fulfilling. Also, as a software developer, seeing my tools being used worldwide is rewarding, where a few hundred lines of code speeds up the research of many.
To end with, I’d like to shoot some rapid-fire questions at you:
- If you could swap jobs for a week, what would you do?
Wouter: I’d be an alpaca farmer.
Bram: A deer farmer in New Zealand. Why not?
- If you could ask an all-knowing being one question, what would it be?
Wouter: Why do we cut round pizza into triangles and put it in square boxes?
Bram: How does Game of Thrones really end?
- What’s the nerdiest thing on your desk?
Wouter: My desktop background—it’s a group photo of the entire human species when the Cassini space probe looked back at Earth to take a picture.
Bram: Mine’s a NASA image of a supermassive black hole. Funny that we both picked space-themed things!
The background images mentioned (©️NASA):
Thank you both!
