Science Unlocked: publication picks from July 2026

In this monthly series, we share a selection of recent publications that use Oxford Nanopore sequencing to unlock novel insights. This month we’ve seen some particularly brilliant methylation publications. Spanning research into inherited myopathies, antibiotic resistance, and haematological malignancies, these studies showcase the scientific advances made possible by Oxford Nanopore sequencing.

Featured in this methylation special edition:

1. Putting our methylation detection to the test

2. Providing the answers for myopathies where short reads fell short

3. Tracing resistance genes back to their pathogenic host

4. Confident methylation calls in minutes for blood cancer classification

5. Separating true-5mC architecture from 5hmC dynamics

Platform capabilities

1. Comparing nanopore sequencing, MethylationEPIC array, and EM-seq for DNA methylation detection (Computational Biology and Chemistry)

DNA methylation mainly occurs at CpG sites and plays a key role in many biological processes, including gene regulation. Methylation profiling is commonly performed using short-read methods, which rely on bisulfite conversion or an enzyme-based alternative. However, these methods face challenges in repetitive or GC-rich regions of the genome. With Oxford Nanopore sequencing, methylation data comes as part of your standard sequencing run, and our any-length reads span complex regions with ease.

Brooks et al. compared Oxford Nanopore sequencing with Illumina’s MethylationEPIC array and enzymatic methyl-seq (EM-seq). From blood samples, nanopore methylation profiles showed high concordance with the EPIC array across ~850,000 shared CpG sites, with strong correlation maintained when nanopore data was downsampled to 10x coverage. On brain tissue samples, nanopore sequencing provided more uniform coverage than EM-seq.

The comparison also highlighted the unique capabilities of nanopore technology — it distinguished 5-methylcytosine (5mC) from 5-hydroxymethylcytosine (5hmC) directly, while EM-seq and the EPIC array only profiled total methylation, missing vital information about gene regulation and disease states. The nanopore reads of unrestricted length also enabled haplotype-specific methylation analysis, providing insights into genomic imprinting, X-chromosome inactivation, and allele-specific methylation.

Read our getting started guide to learn more about investigating methylation in the human genome using nanopore sequencing.

Human genetics

2. Targeted nanopore sequencing enables comprehensive analysis of the genetic and epigenetic landscape of inherited neuromuscular diseases (Nature Communications)

Inherited myopathies are a diagnostic minefield involving over 300 genes and a huge variety of variant types, including single nucleotide polymorphisms, structural variants, repeat expansions, and methylation changes. Yeow and Reis et al. explain that these variants currently require multiple assays to characterise, meaning patients can face a long clinical journey to get answers.

Therefore, the authors introduce a targeted nanopore sequencing assay to capture these variants in a single sequencing run. The method uses ‘Adaptive Sampling to enrich for a ~60 Mbase target panel encompassing all loci implicated in genetic myopathies (n=331 at the time of panel creation in March 2023)’. When applied to suspected myopathy cases that remained unsolved after clinical genetic testing, their nanopore sequencing method identified causative variants in 11/31 individuals. Over half of these were oculopharyngodistal myopathies, which, according to the authors, have no accredited test in Australia.

A key highlight was the team’s new software package, d4z4ling, which resolved repeat number, methylation, and haplotype in one go, helping them to identify challenging facioscapulohumeral muscular dystrophy (FSHD) cases. Ultimately, this nanopore-based assay shows potential to simplify the diagnostic journey for patients with heterogeneous muscle disorders in the future.

Watch André Reis’ talk at London Calling 2026.

Read our white paper on new approaches for clinical research.

Microbiology

3. Nanopore metagenomic sequencing links clinically relevant resistance determinants to pathogens (bioRxiv)

Detecting an antimicrobial resistance (AMR) gene is only half the story — knowing its bacterial host, and whether the gene sits on a mobile plasmid, is what determines its clinical significance. Existing methylation-based plasmid-host association methods, like Nanomotif, work only at the metagenome-assembled genome (MAG) level, which is biased towards abundant taxa and can miss low-abundance pathogens.

To address this limitation, Ürel and Sauerborn et al. built a computational framework known as CUPID (contig- and unassembled-read-based pathogen identification and delineation). They used nanopore sequencing to generate bacterial DNA methylation patterns, and CUPID then linked AMR genes to their pathogenic hosts at the level of individual contigs and even single sequencing reads.

Validated on mock bacterial communities and then on rectal swabs collected during hospital surveillance, the framework reliably distinguished plasmid-encoded AMR genes and associated them with their respective bacterial hosts was confirmed by culture-based testing and whole-genome sequencing.

Watch Lara Urban’s talk at London Calling to hear more about this work.

To see more infectious disease research, check out our blog: how could nanopore sequencing in clinical labs combat infectious disease?

Cancer research

4. Rapid, comprehensive methylation-based classification of haematologic malignancies by nanopore sequencing (medRxiv)

Diagnosing blood cancers often requires a step-by-step approach including morphology, flow cytometry, immunohistochemistry, cytogenetics, fluorescence in situ hybridisation, and targeted or whole-genome sequencing. Each outcome informs the next step, and it can take days or weeks to receive a complete molecular diagnosis. In some cases, the clinic doesn’t have access to the full suite of tests, leaving patients without a full molecular diagnosis and therefore no access to targeted treatments.

To streamline the process, Achterberg et al. have developed Lamprey, a methylation classifier trained on 8,544 research samples to distinguish 86 suspected blood cancer types directly from nanopore sequencing data. Lamprey delivered confident methylation calls within minutes and achieved >98% accuracy on classified cases, outperforming existing methylation-based classifiers ALMA v2 and MARLIN.

Paired with the NASVar variant-calling tool, Lamprey consolidated what is traditionally a time-consuming, multi-step diagnostic workflow into a single same-day molecular test. At ~$82 per sample, the approach could potentially be game-changing for low- and middle-income settings where labs have limited access to the range of tests currently required to diagnose blood cancers.

Hear more about this project in Thomas Alexander’s London Calling talk below.

5. Beyond bisulfite sequencing: resolving 5hmC with nanopore sequencing unmasks the true-5mC methylation entropy landscape (bioRxiv)

Bisulfite sequencing has a blind spot: it can't tell 5mC apart from its derivative, 5hmC. During the workflow, unmodified cytosine residues are converted to uracil and read as thymine. 5mC and 5hmC are protected from conversion, meaning both are read as modified cytosine during sequencing. However, 5mC and 5hmC have different biological roles, so this blind spot has quietly skewed our understanding of methylation entropy, ageing, and cellular plasticity for years.

To address this, Bertocchi et al. developed ShannonPore, a tool for methylation analysis built on Oxford Nanopore sequencing, which differentiates 5mC and 5hmC directly from native DNA. Applying this to human kidney cancer and mouse brain tissue research samples, the team found that patterns previously dismissed as epigenetic noise are often a structured biological signal in disguise.

The standout finding came from the brain samples. Psilocybin-induced neuroplasticity in mice was associated with a distinct rise in methylation pattern diversity, rather than a simple shift in average methylation level, a distinction that bisulfite sequencing would have missed entirely. By resolving true-5mC architecture independently of 5hmC dynamics, this approach could offer novel mechanistic insights into the epigenomic landscapes of development, disease, and pharmacological response in the future.

To find out more ways in which methylation detection is supporting cancer research, read our case study on its potential to support non-invasive cancer monitoring.

Apply Oxford Nanopore sequencing to your own research questions and you'll never see sequencing the same way again. Explore the nanopore sequencing solution.

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