Let's start from the beginning: what is the objective of your platform? The Microarray Unit is a scientific and technological platform of the Josep Carreras Institute. The two main technologies we have are microarrays and Optical Genome Mapping, which we offer to internal and external research groups, as well as to private laboratories. Therefore, our main objective is to make these technologies available to laboratories that don't have them.

Could you explain, in a simple way, what Optical Genome Mapping is? Optical Genome Mapping is like a karyotype, but with higher resolution. In a karyotype, we stain each chromosome pair so that its particular stripe pattern is visible, which will identify which chromosome pair it corresponds to.

In contrast, in Optical Genome Mapping, we use high-molecular-weight DNA sections, which are very long molecules, and, using an enzyme, we add a mark, like a tag, each time a certain sequence appears. These tags generate a pattern specific to each chromosome.

So, what do you get? You obtain a long DNA molecule with a pattern of tags specific to each chromosomal region or each region of DNA. So, you'll be able to see that there's a translocation, for example, because you'll have a DNA molecule in which the first part of the molecule corresponds to one chromosome and the second part to another chromosome.

Therefore, these tags encode each DNA fragment, so you can later identify them. Is that correct? Yes, they give you a pattern. Just like the karyotype, in which the banding pattern identifies each chromosome, here it's the tag pattern. You can see translocations and also other alterations, such as insertions, gains, or losses of DNA. Let's say you have a series of tags, and when you compare it with the reference pattern, you see that your sample is missing some. That means there has been a loss of genetic material. If, on the other hand, there are more tags, it means genetic material has been inserted or gained.

With Optical Genome Mapping, we can obtain a lot of high-resolution information in a single study; that is, we can see much smaller things than with traditional technologies. With karyotyping, you see more alterations; with microarrays, you don't see balanced translocations... in the end, it's like a technique that allows you to combine many techniques into a single experiment.

This information, the changes that have occurred in the chromosomes, what is it good for? Well, it's very useful for analysing patient samples and seeing if they have specific alterations that predict whether or not they will respond to standard treatment, for example. At the research level, it allows us to characterize cell lines that are used as models for many diseases.

Are these alterations we see in DNA related to the development of a disease? In many cases, yes. And this means that in diagnostic laboratories, Optical Genome Mapping can be used to diagnose with a single test. Before, you had to perform two: a karyotype and several FISH tests. With Optical Genome Mapping, you have a comprehensive view of the entire genome and with much higher resolution.

You have presented a set of recommendations recently to use this technique into clinical protocols, along with traditional cytogenetics and molecular tests. What can Optical Genome Mapping offer that isn't already covered by the other two? Optical Genome Mapping offers higher resolution than microarrays, FISH, or karyotyping. In these cases, you can obtain the same or better information with a single methodology. However, it's not suitable for the analysis of point mutations in DNA, which still requires the use of sequencing methodologies.

What do you mean when you say it achieves higher resolution? Well, karyotype analysis shows alterations on the order of 5-10 megabases (millions of nucleotides), microarrays can detect 50 kilobases (thousands of nucleotides), and with Optical Genome Mapping, you can go down to 10 kilobases, depending on the region. Therefore, it allows for the detection of smaller alterations that would go unnoticed with other methodologies.

So, your recommendation as an expert is to implement this methodology in clinical protocols? Exactly, we are part of two Optical Genome Mapping working groups, one national and one international, with laboratories from the rest of Europe and the United States. The group's latest article proposes guidelines for determining which techniques to apply depending on the pathology. For example, in patients with a neoplasm where the importance of translocations is known, it doesn't make sense to look at point mutations, but it does make sense to use Optical Genome Mapping, which is precisely its strength.

What is needed to integrate this technology into routine clinical diagnostic procedures? If we're talking about public hospital laboratories, all that's needed is for management to commit to this technology. The technology is ready, and there are many articles showing that Optical Genome Mapping's concordance with traditional techniques is almost 100%. This is data you can sell to Medical Management to go from several diagnostic tests to just one, which somehow integrates them all.

What's the advantage? Is it cheaper or faster? Why would you want to replace the current tests with this new one? The advantage, basically, is that you can have everything with a single study. In routine cytogenetics laboratories, many karyotypes and FISH tests are performed. Karyotyping is a cheap technique in terms of reagents, and FISH is relatively inexpensive, but it's targeted and can only analyze one alteration at a time. If you need to check for four different translocations, the cost quadruples. With Optical Genome Mapping, for the price of four FISH tests, you'll have all the genome information.

Is it currently possible to perform this integration from a technical or trained personnel standpoint? Yes, in fact, more and more hospitals are purchasing the equipment to do it. On a technical level, you must undergo training to begin the procedure. I must also say that it's a technology that requires some experience, and over time you learn how to apply it, especially with difficult samples.

As pioneers and specialists, do you offer this type of training? Yes. Although the company requires mandatory training when you purchase the equipment, we've helped people who didn't yet have the necessary experience and welcomed them into the unit to see how we work on the most complicated aspects, such as DNA extraction and labelling.

Optical Genome Mapping is very focused on haematological diseases. Can it be used outside of this field? Is it useful in other contexts? Yes, it's also being used in solid tumours, but at the research level. At the diagnostic level, we're still a bit far from implementing it. There are several articles that apply it, but it's problematic because solid tumours are very heterogeneous. Since Optical Genome Mapping is a technique that analyses the DNA of millions of cells together, it suffers when there are very different cells in the sample. In comparison, haematological malignancies are much more homogeneous and are often associated with a single alteration.

Outside of cancer, it could also be useful for studying genetic changes in children with malformations, for example.

How do you see this technology in five years? We've been working on it for some time now, and it's becoming more reliable and more robust. This has also happened with technologies that are now fully established but initially raised questions, such as microarrays. In five years, it's sure to be much more established. Furthermore, companies are investing in robots so that everything is automated, less manual, which is often scary, because in the end, you're working with precious samples, and it requires processing time.