“Reading DNA is a story of ever more, ever faster, and ever cheaper"

BRIGHTcore’s newest addition — the MGI DNBSEQ-T7 — is about the size of a modest wardrobe, but behind its sleek black mirror glass lies the very best in DNA sequencing technology. And for that price, it should be.

Any numbers to put on that?
Toon Janssen: “We carry out between 28,000 and 32,000 analyses a year. Around a third of those are NIPT tests, which we perform in collaboration with the genetics department. These are non-invasive prenatal blood tests for pregnant women that can detect certain chromosomal abnormalities in the baby, such as Down syndrome.”

NIPT is now a standard clinical test.
“That shows just how quickly sequencing has evolved. Twenty years ago, a DNA analysis was still exotic, time-consuming, and extremely expensive. Today, the technology is routine and affordable — both in clinical settings and scientific research. The growth of BRIGHTcore has mirrored that evolution. We started ten years ago with a single sequencer in the Laboratory of Medical Genetics. It was mainly used for fundamental research into rare diseases, including work by the GRAD research group. Thanks to co-financing from our partners, we’ve been able to keep investing over the years — in new equipment as well as IT infrastructure.”    

"Understanding how cancer cells are mutated and how they are genetically structured is crucial for treatment"
 

Is IT a major part of your operations?
“Absolutely. Half of our budget goes towards storage capacity and computing power, and five of our ten staff members are bioinformaticians. A human genome contains three trillion base pairs. Storing that amount of data requires a huge amount of space. At the moment, we’re managing around two petabytes — that’s two million gigabytes. For privacy reasons, we currently store all that data locally, here in Jette and at the Nexus Datacentre in Zellik. In addition, immense computing power is needed to map out the genomes in question. Thanks to the arrival of graphical processing units, or GPUs, that process has become much faster. Before that, computing power was a major bottleneck in DNA sequencing.”    

Are there other developments in the pipeline?
“Research is increasingly focusing not just on the genetic profile of the tumour, but also on that of the patient. The more we learn about heredity, the clearer it becomes that many diseases have a strong genetic basis. Who develops a tumour, what type of tumour it is, and at what age it appears — all of that is largely influenced by your DNA, though environmental factors also play a role. The same goes for how people respond to medication. What works well for one patient might have no effect at all on another. It’s only by fully understanding these processes that we can develop the most effective, personalised treatments. That’s what this new field of research is all about: pharmacogenetics.”

Does this also apply to other medical specialties?
“Take dermatology, for instance. Patients with different skin conditions are often prescribed the same treatment — for example, a corticoid-based cream. But we know that this doesn’t work equally well for every patient or condition. Together with the Skin Research Group led by Professor Jan Gutermuth, we’re now using genetic sequencing of skin biopsies to identify which immunological responses are involved. That way, we hope to predict how patients will respond to specific treatments. Again, it’s all about personalised medicine.”

Do you collaborate with many different disciplines?
“That’s what makes the work so fascinating. Within the faculty of medicine, there are hardly any research groups we don’t interact with — nearly everyone uses some form of sequencing. We offer around twenty different types, such as genome sequencing, RNA sequencing, methylation sequencing, and so on. The technology we choose depends on which part of the genetic material we want to map out.”

I sense there’s a “but” coming.
“Single-cell sequencing is an improvement on bulk sequencing, where the tissue was just ground up. But with single-cell sequencing, you still don’t know exactly where each cell came from. Which types of cancer cells are located where in the tumour? In the centre? At the edges? Spatial transcriptomics allows you to answer those questions. In this technique, a thin slice of tissue is placed on a glass slide covered in thousands of barcoded probes. These probes capture genetic material, tag each molecule with a location code, and then analyse everything via sequencing. The result is a kind of map of gene activity across the entire tissue — showing exactly which cell is where and what it’s doing. To refine our spatial transcriptomics work, we’re currently collaborating with the pathology department and the research group led by Professor Ilse Rooman.”

“The past twenty years have seen a real revolution: devices can do more and work faster than ever before.”

Does this require increasingly advanced sequencers?
“Absolutely. Over the past twenty years, we’ve seen a real revolution in this area as well — machines that can handle more and more analyses in less and less time. The current highlight at BRIGHTcore is the MGI DNBSEQ-T7. That system can run four sequencing cycles overnight, each one processing sixteen human genomes. For now, that’s sufficient, but in a few years’ time, it’ll likely be too limited again — the demand from both hospitals and the research community keeps growing. That’s why we’ve recently submitted a new FWO grant application to fund the purchase of our next sequencer, which will be able to deliver results in just five hours. And this evolution is only going to accelerate.”

Especially if another pandemic hits us!
“During the COVID-19 pandemic, in collaboration with microbiology, we were indeed one of the centres that performed genotyping of the various COVID variants. That too is sequencing. We also do it for bacteria and other micro-organisms. It’s essential for determining which antibiotics are most appropriate, or for tracking infectious disease outbreaks. Take the recent STEC bacterium, for example. That dangerous strain of E. coli caused serious health problems and even deaths in several Belgian care homes. By genetically characterising such bacteria, we can trace how they spread.”