Science Unlocked: publication picks from January 2026
In this monthly series, we share a selection of recent publications that use Oxford Nanopore sequencing to unlock novel insights. Spanning rare disease, cancer organoids, and gene therapy research, these studies showcase the advances in scientific research made possible by Oxford Nanopore sequencing.
Featured in this edition:
1. RAPID insights into rare disease splicing
2. Accurate tumour sample classification after a decade in storage
3. Spatial transcriptomics of kidney cancer organoids
4. Targeting over 3,000 known viruses at once
5. Investigating liver toxicity after gene therapy
Human genetics
1. RAPID: a targeted long-read RNA workflow for functional resolution of splicing variants in rare disease (medRxiv)
Montgomery et al. introduce RAPID, a targeted nanopore cDNA sequencing workflow built to tackle the challenges of investigating rare diseases. Applied to six previously unsolved cases, RAPID delivered functional answers every time — confirming splice-disrupting variants, ruling genes out, or zeroing in on elusive second alleles that short-read sequencing couldn’t resolve.
By capturing near-full-length transcripts from blood, the approach supports single-sample interpretation, with low costs and results in as little as two days. It’s a practical demonstration of what nanopore cDNA sequencing does best: turning transcript complexity into clarity, and showing promise for supporting rare disease diagnostics in the future.
‘Up to 62% of pathogenic single-nucleotide variants are estimated to affect splicing, underscoring the value of functional, transcript-guided follow-up in uncovering missed splice or regulatory defects’
Montgomery, K. et al.1
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Figure 1. The end-to-end RAPID workflow. (A) Preparation of cDNA sequencing libraries from blood or fibroblasts. B) Data analysis pipeline, including quality control, alignment to the human reference genome, transcript assembly, and quantification. Figure redistributed from Montgomery et al. 20261 under Creative Commons Attribution License CC BY 4.0.
Here’s more research striving to end the rare disease diagnostic odyssey by harnessing the power of nanopore sequencing.
Cancer research
2. Feasibility of long-read nanopore sequencing for methylation-based classification of posterior fossa ependymomas (Brain Tumour Pathology)
When tissue is scarce, accuracy is critical in unravelling complex cancer biology. In this study, Yamada and Takimoto et al. show how nanopore sequencing can pull out critical details from paediatric posterior fossa brain tumours, even when samples have been sitting in a freezer for more than a decade. Epigenetic profiling is vital for classifying posterior fossa group B tumours as recurrent coding alterations in these cancers are still mostly unidentified.
Using PCR-free nanopore sequencing, the researchers produced methylation profiles that aligned closely with established array-based methods, only faster and without the need for damaging bisulfite conversion. In a single run, those methylation profiles sit alongside single nucleotide variants, copy number estimates, and structural variant information. It’s a streamlined, all-in-one approach that could provide richer insights for tumour characterisation — especially when time and tissue are in short supply.
‘Nanopore-based methylation profiling required approximately 2–3 days from DNA extraction to classification, whereas outsourced EPIC array analysis typically required 1.5–2.5 months’
Yamada and Takimoto et al.2
Find out how you could unlock transformative cancer insights.
3. Long-read spatial transcriptomics of patient-derived clear cell renal cell carcinoma organoids identifies heterogeneity and transcriptional remodelling following NUC-7738 treatment (Cancers)
Tumours aren’t uniform, and this study by Abdullah et al. explores their molecular complexity. By combining nanopore sequencing with spatial transcriptomics, the team mapped gene and isoform expression across patient-derived kidney cancer organoids, which preserve the tumour’s original structure and cellular diversity. This revealed clear regional differences in metabolism, protein synthesis, and immune-related pathways, alongside spatially distinct use of key transcript isoforms.
Following treatment with the experimental compound NUC-7738, spatial profiling captured widespread, but region-specific, transcriptional remodelling. The approach uncovered layers of tumour heterogeneity that would be invisible in bulk or short-read data, offering a powerful research framework for studying tumour biology and treatment response in physiologically relevant models.
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Figure 2. Differential gene expression and spatial analysis highlights the heterogeneous expression of three genes between control and NUC-7738-treated clear cell renal cell carcinoma organoids. Figure adapted from Abdullah et al. 20263 under Creative Commons Attribution License CC BY 4.0.
Check out our workflow overview for single-cell transcriptomics.
Microbiology and infectious disease
4. Twist-ONT: combining nanopore sequencing with the twist comprehensive viral research panel (Virology)
When viral genomes are buried under mountains of host DNA, finding the signal that matters can be tough. In this study, Haars et al. present Twist-ONT, a targeted workflow that combines the Twist Comprehensive Viral Research Panel with Oxford Nanopore sequencing to bring viral sequences to the surface. Applied to PCR-positive swab and plasma samples, the approach enabled broad viral detection, reliable species classification, and high-quality whole-genome assemblies from a single run.
By enriching for viruses upfront, Twist-ONT reduces background noise and takes advantage of long reads to deliver more complete genomes and clearer insight into viral diversity than untargeted or short-read methods. For researchers working in virology, surveillance, or metagenomics, this is an approach that could level up your viral genomics workflows.
‘[Oxford Nanopore] sequencing has several advantages over other sequencing methods, combining long sequence reads and scalability, making it well-suited for virome analysis’
Haars, J. et al.4
See how we’re changing the game for pathogen surveillance.
Biopharma
5. Contaminating plasmid sequences and disrupted vector genomes in the liver following adeno-associated virus gene therapy (Nature Medicine)
Gene therapy vectors don’t always behave as we’d like, and this study by Buddle and Brown et al. shows why seeing the full picture matters. Using a combination of Oxford Nanopore and short-read metagenomic sequencing, the researchers examined a liver tissue research sample from a child who developed severe hepatitis after adeno-associated virus (AAV)-based gene therapy.
Our technology surpassed the limitations of short-read sequencing, revealing complex concatemeric structures, disrupted vector genomes, fragments of manufacturing plasmids persisting in the liver, and vector–human junctions. While further work is needed to understand how widespread these findings are, the approach points to the future potential of nanopore metagenomic sequencing as a powerful tool for investigating gene therapy manufacturing quality and safety.
Discover how we can support every stage of the biopharma drug development pipeline.
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