Science unlocked: publication picks from June 2025

In this monthly series, we share a selection of recent publications in which Oxford Nanopore sequencing was used to unlock novel insights. Spanning from direct RNA transcriptomics, to complex diseases, to single cell research, these studies showcase the advances in scientific research made possible by Oxford Nanopore sequencing.

Featured in this edition:

1. Broadening the global picture of ataxia

2. The rapid RNA modifications behind type 2 diabetes

3. Bird flu in retail dairy products

4. An RNA atlas of the ageing mouse brain

Human genetics

1. Identification of GGC repeat expansions in ZFHX3 among Chilean movement disorder patients (Movement Disorders)

Saffie-Awad et al. identified the first ZFHX3 GGC repeat expansions associated with spinocerebellar ataxia type 4 (SCA4) in Latin America. Their findings link longer repeats to earlier onset, demonstrate repeat instability and epigenetic changes, and illustrate the potential of Oxford Nanopore sequencing for future use in hereditary ataxia research and screening.

Key points:

• Four Chilean patients were found to have ZFHX3 GGC repeat expansions (47–55 units), the first such cases outside Northern Europe

• All showed classic SCA4 symptoms, and one case also involved parkinsonism, broadening the known clinical spectrum

• Longer expansions were associated with more severe disease and earlier onset

• One family exhibited intergenerational repeat expansion from 49 to 55 units, confirming repeat instability

• Allele-specific hypermethylation was observed, suggesting an epigenetic role in disease pathogenesis

• No repeats ≥42 units were found among 438 diverse controls, reinforcing the threshold for pathogenicity

Figure: schematic overview of the study design. Blood samples were taken from 15 individuals with suspected hereditary movement disorders. The extracted DNA was sequenced on a PromethION device. Variant calling included single nucleotide variants (SNV), structural variants (SV), and short tandem repeats (STR). The researchers identified pathogenic ZFHX3 GGC expansions in four individuals. Figure redistributed from Saffie-Awad et al. 2025 under Creative Commons Attribution License CC BY 4.0.

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2. Direct RNA nanopore sequencing reveals rapid RNA modification changes following glucose stimulation of human pancreatic beta-cell lines (bioRxiv)

Mulroney, Taylor, and Lee et al. used Oxford Nanopore direct RNA sequencing to investigate how glucose levels affect RNA modifications in human pancreatic beta cells, uncovering thousands of glucose-responsive changes. The study reveals that these modifications, especially m⁶A, are enriched in type 2 diabetes–related genes and act independently of gene expression, offering new insights into RNA-based regulation in diabetes.

Key points:

• The team profiled four RNA modifications: m⁶A, m⁵C, inosine, and pseudouridine

• Of the 2.7 million sites detected, 1,697 showed significant changes after glucose stimulation

• Most modification changes occurred without changes in gene or transcript expression, indicating distinct regulatory mechanisms

• m⁶A dominated among altered sites and was enriched in key diabetes genes

• This is thought to be the first report of glucose-responsive changes in m⁵C, inosine, and pseudouridine in beta cells

• Oxford Nanopore sequencing enabled simultaneous, isoform-level analysis of all modifications in one assay

Figure: EndoC-BH1 (top) and EndoC-BH3 (bottom) were cultured in low glucose condition (2.8 mM, blue) or high glucose condition (15.0 mM, yellow). RNA was extracted from each culture and used to prepare native direct RNA sequencing libraries (which retain RNA modifications), or in vitro transcribed (IVT) RNA sequencing libraries, where RNA modifications are lost during complementary (c)DNA synthesis. Figure redistributed from Mulroney, Taylor and Lee et al. 2025 under Creative Commons Attribution License CC BY 4.0.

See what insights you could unlock with Oxford Nanopore direct RNA sequencing

Infectious disease

3. Amplicon sequencing of pasteurised retail dairy enables genomic surveillance of H5N1 avian influenza virus in United States cattle (PLOS One)

Lail et al. used tiled-amplicon Oxford Nanopore sequencing to detect and characterise H5N1 virus in pasteurised dairy, achieving over 90% genome coverage in viral RNA-positive samples. This method offers a rapid, accessible surveillance solution in regions without on-farm testing, supporting early detection and response to viral spread.

Key points:

• Highly pathogenic avian influenza viruses are infecting humans and US dairy cattle, raising public health concerns

• Surveillance gaps exist where on-farm testing is unavailable

• Oxford Nanopore sequencing provided over 90% genome coverage at greater than 20x depth in 5/13 viral RNA-positive dairy samples

• Viral sequences clustered with other cattle outbreak strains but showed no state-level grouping

• Their findings suggest either inter-state viral movement or limited sequence variation

• A scalable approach, such as Oxford Nanopore sequencing, could enhance genomic surveillance using easily accessible sample types

• Early detection from retail products may aid a rapid response and outbreak prevention

Read more on viral amplicon sequencing with Oxford Nanopore technology

Single cell

4. Cell-specific RNA isoform remodelling in the ageing mouse brain (bioRxiv)

Using Oxford Nanopore sequencing, Rehman et al. built a full-length RNA isoform atlas in two regions of the mouse brain, revealing thousands of cell-type and age-related transcript changes. This enabled unprecedented insights into ageing biology and neurodegeneration, offering a path to earlier detection and intervention for age-linked brain disorders in the future.

Key points:

• The atlas captured transcriptomic changes across 51 cortex and hippocampus samples from male and female mice across four age groups

• Rehman et al. identified over 3,700 cell-type-specific and over 4,700 age-associated isoform changes

• Immune and oligodendrocyte cells showed the greatest isoform diversity

• Ageing was linked to longer, coding isoforms due to shifts in transcription start and end sites

• Neuronal isoforms were most strongly downregulated with age, suggesting significant transcriptomic remodelling and potential vulnerability to neurodegeneration

• The proportion of senescent immune cells rose sharply with age, particularly in the hippocampus and in females

• Oxford Nanopore sequencing enabled the analysis of full-length native RNA at the single-cell level, offering a powerful tool for studying ageing biology and advancing early detection strategies for brain disorders

Figure: schematic of experimental workflow to map the cellular and regional transcriptomic landscape of the ageing mouse brain with Oxford Nanopore sequencing. Hippocampus and cortex samples were taken postmortem from male and female mice from across four age groups. The brain tissue was dissociated into single cells, which were then encapsulated individually in droplets with a barcoded bead and reverse transcriptase. Each RNA transcript was tagged with a unique molecular identifier (UMI). The barcoded cDNA from all the cells was then amplified for Oxford Nanopore sequencing. Figure made available for use by Rehman et al. under a CC0 license.

Check out our workflow overview for single-cell transcriptomics

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