Using food research expertise for genetic diagnostics

Whether it’s developing and proving the viability of low-cost sequencing technology, or it’s creating new methods for genetic screening, data is the name of the game for Associate Professor Lukasz Krych, who’s on the promotion programme at the Department of Food Science, working in the Section for Food Microbiology, Gut Health and Fermentation.

He specializes in bioinformatics, multivariate data analysis, and developing the use and applicability of high throughput DNA sequencing – technologies that efficiently analyze large amounts of samples at the same time, e.g. to screen for genetic disorders DNA samples, or pathogen detection in food.

“As a molecular biologist, I have always been fascinated by the DNA molecule. How can a nearly 2-meter-long strand, composed of billions of letters written in a four-letter code, fit into a 20-micrometer human cell and still convey all the necessary information? It’s like fitting a 2,000-kilometer string into a tennis ball. That fascination is why I have developed applications to study microorganisms through their DNA throughout my career,” says Lukasz Krych.

And Lukasz’ expertise in sequencing technology, and creative use of it, has recently resulted in two publications: One as a proof-of-precision of Oxford Nanopore Technology, and one using the same technology for a new and non-invasive way to do screening of genetic disorders in humans.

Win-win sequencing

Throughout Lukasz’ career, his go-to sequencing technology has been Oxford Nanopore Technology (ONT), despite there having been some critique of its precision in the academic community. A significant upside of ONT, however, has been its affordability, costing around 1000 euro, making the technology broadly accessible. The competitors offer their equipment for hundreds of thousands of euros.

“I got my first ONT-device almost 10 years ago, and at that time, it was more about guessing the DNA sequence than accurately reading it. But even back then, the potential was indisputable. There were bigger companies that had a solid hold on the market, but I believed that this technology had a promising future, and that once its sequencing quality was resolved, it would eventually outcompete its competitors thanks its affordability, reusability and real-time data analysis,” explains Lukasz.

This year, Lukasz and colleagues have played a significant part in resolving ONT’s issues with sequencing quality. They’ve managed to make its results as precise as its significantly more expensive counterparts, which you can read the published work of here.

In the paper, they used the bacterium Propionibacterium freudenreichii, a crucial organism in the fermented foods, as the test case, as it’s notoriously difficult to reconstruct. And besides assembling high-quality genomes of the bacteria, as high as ONT’s competitors, they could even study epigenetic modifications, changes in the gene expression, with their analysis – a first for this type of accessible sequencing technology.

“It’s like the electric engine in the age of efficient diesel engines being held back by a single limitation: range. But in our recent paper, we demonstrated that the ‘range’ of nanopore sequencing is now comparable to any long-range diesel engine, yet the cost of the technology is 100 times lower, and its use is order of magnitude cheaper. There’s a slight feeling of satisfaction in this, too: that eventually we were right about ONT’s potential,” says Lukasz.

Bridging the gap to medical science

While Lukasz’ work has primarily been focused on microbial DNA and the microbes’ effect on gut health from a food science perspective, especially the sequencing expertise that he and his colleagues have gained is transferable to other fields, including medical science.

Exactly this is what Lukasz and colleagues have done by developing what they’ve dubbed SCAN. It’s an affordable, quick, and non-invasive screening tool using ONT to detect genetic disorders caused by abnormal amounts of chromosomes in newborns.

“The medical world is, in many ways, highly unique. Due to the high standards and the need for certifications, there is often a delay before modern technologies from universities can be implemented in the medical sector. With SCAN, we were the first to demonstrate that low-cost equipment for DNA sequencing can be used to develop a fully certified solution for the mass-scale detection of genetic disorders. Our method allows for the simultaneous analysis of hundreds of samples (patients), further reducing costs and making DNA analysis comparable in price to traditional blood testing,” says Lukasz Krych 

Lukasz and his colleagues currently have a proof-of-concept study on SCAN’s recently published in Human Genomics, wherein they have used Klinefelter Syndrome as the test case. SCAN is now the world’s first IVD-certified genetic test, and it achieved 100% sensitivity, specificity, and accuracy – all from a simple buccal swap. For comparison, the same results would normally require invasive procedures or expensive testing.

With the continued development of sequencing technologies, Lukasz sees his field opening even up even further, and enabling new exciting avenues of research, which is something he is looking forward to.

“My main motivation is to explore a new area of research: epigenetics. In our recent publication, we demonstrated that nanopore technology can not only read the order of letters in a DNA sequence very accurately but also detect chemical attachments, such as methylations, that alter how DNA is used. Although studying these modifications was possible in the past, it was extremely expensive. Now, we can investigate them at no additional cost to DNA sequencing. This is very exciting for us as it opens up an entirely new area of research. We can begin to understand how bacteria with the exact same genetic material can behave differently under various conditions. Epigenetics is key to understanding how the same DNA sequence in a skin cell and a bone cell can produce entirely different cell types with unique properties,” ends Lukasz Krych.