Science unlocked: publication picks from July 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 Alzheimer’s disease research, to malaria surveillance, to non-invasive cancer classification, these studies showcase the advances in scientific research made possible by Oxford Nanopore sequencing.

Featured in this edition:

1. Expanding our knowledge of human diversity

2. A new phase in Alzheimer’s disease research

3. Enhancing malaria surveillance in Africa

4. Detecting gene fusions in cancer

5. Non-invasive cancer classification

Human genomics

1. Structural variation in 1,019 diverse humans based on long-read sequencing (Nature)

Schloissnig and Pani et al. harnessed Oxford Nanopore technology to analyse structural variants (SVs) in 1,019 diverse human genomes, uncovering more than 100,000 SVs and genotyping 300,000 repeat regions — many invisible to short-read methods. This open-access dataset captures rare, ancestry-specific, and disease-associated variants, offering a valuable tool for advancing rare disease research and population genomics.

Key points:

• The team used participants from the 1000 Genomes Project spanning 26 populations

• They developed the SV analysis by graph augmentation (SAGA) framework to detect SVs more accurately

• Many of the SVs were formed by DNA repair processes involving repeated sequences

• Certain deletions were consistently detected across different people

• Most SVs were rare or specific to certain populations, especially in samples from African participants, and some were found in or near genes linked to disease

• This open-access resource could help narrow down genetic variants in rare disease studies, improve understanding of genetic risk, and promote equitable and global progress in precision medicine in the future.

Figure: breakdown of self-identified geographical ancestries for 1,019 Oxford Nanopore genomes representing 26 populations from five continental regions. The three-letter codes used are equivalent to those used in the 1000 Genomes Project phase III. Figure redistributed from Schloissnig and Pani et al. 2025 under Creative Commons Attribution License CC BY 4.0.

Read our large cohort sequencing workflow overview

2. Haplotype-resolved DNA methylation at the APOE locus identifies allele-specific epigenetic signatures relevant to Alzheimer's disease risk (bioRxiv)

Genner et al. used Oxford Nanopore sequencing to map allele-specific methylation at the APOE locus — a gene central to Alzheimer’s disease risk — in postmortem brain research samples. They uncovered novel haplotype-resolved methylation signatures without the need for bisulfite conversion, far surpassing short-read methods. This study showcases the power of nanopore sequencing for high-resolution, phased epigenetic analysis in neurodegenerative disease research.

Key points:

• 332 postmortem brain research samples were analysed using Oxford Nanopore sequencing

• The team discovered 18 novel allele-specific CpG methylation sites at the APOE locus

• Oxford Nanopore sequencing detected 1,556 CpG sites, compared with only 46 by short-read array methods

• Genner et al. observed APOE ε2-specific methylation patterns, possibly linked to protective effects against Alzheimer’s disease

• This research is likely the most comprehensive haplotype-resolved APOE methylation study in human brain tissue to date

Figure: overview of the Illumina methylation array-based pipeline used for genotype-level methylation detection (top) compared with the Oxford Nanopore sequencing pipeline (bottom), which can phase haplotypes to provide allele-specific methylation analysis. Figure made available for use by Genner et al. under a CC0 license.

Check out our getting started guide for methylation

Infectious disease

3. Continental-scale genomic surveillance of Plasmodium falciparum malaria with rapid nanopore sequencing (bioRxiv)

To support real-time malaria surveillance in sub-Saharan Africa, Mwenda et al. investigated the use of Oxford Nanopore sequencing to analyse over 1,000 dried blood spots. This low-cost, portable method accurately detected drug-resistance mutations and gene deletions associated with diagnostic test evasion, even at low parasite levels — offering an accessible, rapid solution for local labs to monitor outbreaks and guide public health responses.

Key points:

• The parasite Plasmodium falciparum is evolving to evade diagnosis and treatment through the deletion of diagnostic marker genes and acquisition of drug resistance mutations

• Oxford Nanopore sequencing provided consistent performance across labs and parasitemia levels, accurately detecting hrp2/3 gene deletions and antimalarial drug-resistant mutations

• The Oxford Nanopore protocol was deemed to be low-cost (<$25/sample), rapid (under 29 hours from DNA extraction to results), and required less than half the pipetting steps of an Illumina-based protocol

• This work was carried out with minimal IT needs — ideal for resource-limited settings

Figure: overview of sequencing approach and implementation across sub-Saharan Africa. (a) P. falciparum-positive dried-blood spots (DBS) are the source material for DNA extraction. From extracted DNA to sequencing takes five hours. (b) Data analysis occurs in real-time on a laptop. While sequencing is ongoing, quality control (QC) and variant calling results are displayed to an interactive dashboard. GPU: graphics processor unit. Sequencing time depends on flow cell quality and number of samples. (c) DBS samples were processed from eight countries across sub-Saharan Africa. For six countries, all sequencing occurred locally (filled circles); for two countries, samples were sequenced internationally (Mali, Ethiopia; open circles). (d) Timeline of sequencing runs. Size of point indicates number of samples per run. Total sequencing runs for each country is shown in a box at right. (e) Barplot displaying total number of samples sequenced per country. Overall, 1,065/1,404 (65.8%) of samples were processed in Africa. Figure redistributed from Mwenda et al. 2025 under Creative Commons Attribution License CC BY 4.0.

Learn more about pathogen surveillance in our white paper.

Cancer research

4. Combining panel-based and whole-transcriptome-based gene fusion detection by long-read sequencing (Cell Reports Methods)

The Children’s Hospital of Philadelphia (CHOP) cancer fusion panel uses short-read sequencing to target 119 oncogenes commonly implicated in cancer gene fusions (GFs), but is limited by read length, target scope, and a 14–21-day turnaround. Rybacki et al. adapted libraries from the panel for targeted Oxford Nanopore sequencing and combined them with whole-transcriptome sequencing for panel-negative cases. They achieved a faster turnaround time and identified novel GFs, demonstrating rapid and comprehensive fusion detection with future potential for use in the clinic.

Key points:

• Cohort 1 consisted of 29 panel-positive samples analysed by panel-adapted sequencing to assess the Oxford Nanopore workflow against the clinical-validated short-read protocol

• Cohort 2, consisting of 24 panel-negative samples, was subjected to Oxford Nanopore whole-transcriptome sequencing to assess the capabilities of nanopore technology to detect novel GFs overlooked by short-read sequencing

• Oxford Nanopore sequencing successfully detected known GFs in panel-positive samples, confirming compatibility

• 20 novel GFs were discovered by whole-transcriptome sequencing; all validated by PCR and Sanger sequencing

• Nanopore sequencing reduced the turnaround time to <48 hours, compared with 14–21 days with short-read workflows

• The method showed strong performance regardless of sample collection type, even formalin-fixed paraffin-embedded tissue

See our workflow overview on bulk transcriptomics

5. RNA liquid biopsy via nanopore sequencing for novel biomarker discovery and cancer early detection (bioRxiv)

Using Oxford Nanopore sequencing, Peddu and Hill et al. profiled full-length cell-free RNA from blood plasma and uncovered over 270,000 novel transcripts — far beyond the reach of short-read methods. Utilising machine learning models, the team classified early stage oesophageal cancer and precancer with 100% sensitivity and specificity, demonstrating the potential of nanopore sequencing as a non-invasive tool for early cancer detection and monitoring.

Key points:

• Short-read sequencing methods fail to capture full-length cell-free RNAs (cfRNAs), limiting biomarker discovery and early disease detection

• This study used Oxford Nanopore sequencing of cfRNA from 47 plasma samples (healthy, precancer, and cancer) and identified over 270,000 previously unannotated transcripts

• A custom transcriptome was created by integrating these novel transcripts with known annotations, enabling comprehensive quantification and analysis

• Mitochondrial RNAs and immune checkpoint genes (e.g. CTLA-4, LAG-3) were enriched in disease states, highlighting their potential as early biomarkers and therapeutic targets

• This nanopore-based liquid biopsy platform has the potential to offer a sensitive, non-invasive tool for early cancer detection and monitoring

Figure: the authors developed a new RNA liquid biopsy platform technology called LOCATE-seq that harnesses Oxford Nanopore sequencing of cfRNA to annotate and quantify known and novel transcripts. In the future, this could be used to enable disease detection/monitoring, treatment selection, and drug discovery. Figure redistributed from Peddu and Hill et al. 2025 under Creative Commons Attribution License CC BY 4.0.

Watch lead author Daniel Kim’s talk at London Calling 2024, or catch a summary in his vox pop below:

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