The frontier of omics applications
By Sissel Juul, VP, Applications, Oxford Nanopore Technologies
At Oxford Nanopore, our Applications Team sits right at the intersection of practicality and possibility. We act as an internal customer, not only asking if something can be done, but also where it can be useful, scalable, and meaningful to our community.
This is what makes London Calling feel special. It’s our chance to deepen our relationships with the community and to start new collaborations that push the boundaries even further. This time, we showcased some new collaborative work from the past year. I’m especially excited about the new tools for assembly, as they are already making genomics simpler and more accessible.
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Making telomere-to-telomere genome assembly faster, simpler, and more accessible
High-quality, telomere-to-telomere (T2T) assemblies have the potential to set a new gold standard in genomics. However, until recently, they were technically difficult, resource intensive, and a luxury reserved for specialised labs. That is now changing.
Working closely with collaborators at A*STAR Genome Institute of Singapore, National Human Genome Research Institute, and National Institutes of Health, and our machine learning teams, we have improved the comprehensiveness of nanopore-only whole-genome sequencing dramatically, to assemble entire genomes using ultra-long Oxford Nanopore reads. For researchers who do not have access to ultra-long reads, or have limited computational resources, our partners at Yale University, Dana-Farber Cancer Institute, and Harvard University have created new software, hifiasm-ONT, that achieves similar results even with standard Oxford Nanopore sequencing runs.
This development marks a shift from complexity and trade-offs to simplicity and accessibility, making it far easier to scale high-quality genome assembly on a single platform. It is a development that we are genuinely excited about, as it opens new possibilities in population-scale studies, biodiversity research, and even potential for routine T2T clinical genomics. The team cannot wait to see what the community does with it.
Integrated insights from a single dataset
Traditionally, if you wanted to look at small and large genetic variants, methylation, and large structural changes, you needed three separate techniques — or even technologies. In addition to our talk, we wanted to demonstrate our work in a couple of examples of how, using Oxford Nanopore sequencing, you can get all of that from a single run. Our integrated multiomic approach captures SNVs, structural variants (SVs), and methylation with no special chemistry needed.
Our work showing this approach in challenging clinically relevant genes like MECP2, SMN1/2, and CYP2D6 is already helping researchers understand diseases like Rett syndrome and spinal muscular atrophy, and drug metabolism. By looking at the full multiomic picture from a sample, we can see subtle differences that explain why people with the same genetic mutation can have completely different phenotypes. Similarly, by transferring our multiomic approach to cancer research, we can now see how different genetic layers interact, helping researchers understand disease progression better than ever before.
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Scaling metagenomics with complete, strain-resolved assemblies
In microbial research, context is everything. Unfortunately, it is often the first thing lost in metagenomics. We might learn what is present, but the parts that make up the whole remain hidden. Legacy approaches can shed light on these component parts of a sample. However, by fragmenting microbial genomes, these approaches can strip away the links that matter: which genes are doing the work, how they interact, and the dynamics across the community.
What if, instead, you could get the full picture — what microbes are present, where they interact, and how this all fits together — from a single sample? That is exactly what MetaMDBG, a new tool developed by Gaëtan Benoit and the Quince group at the Earlham Institute, makes possible. Researchers can now quickly assemble clear, complete genomes of microbes from complex environmental samples and directly link key functions, like antibiotic resistance, to specific organisms.
We sequenced a complex environmental sample to very high depth (1.4 terabases) to benchmark this new tool and will be releasing this data to the community to help further tool and quality control development. The use of this cutting-edge analysis software and native DNA sequencing now make it easier to go from soil or gut sample to functionally annotated genomes. This opens the door for better antimicrobial resistance tracking, environmental microbiology, and industrial applications.
The thing that excites us the most, though, isn’t any single advancement, but the momentum being created as these are picked up and extended by our collaborators around the world. From the potential for rare disease diagnostics to environmental metagenomics, this is our global community’s innovation rapidly becoming impact. Seeing how quickly the community builds on our work tells us we are on the right track.
I invite you to watch the talk, which the whole team and all our collaborators contributed to, and please drop me a line with any questions, or to let me know if you would like to collaborate.