Science unlocked: publication picks from June 2024

In this monthly series, we share a selection of recent publications in which nanopore sequencing was used to unlock novel insights. Spanning from human genetics and clinical research to infectious disease, agrigenomics, and conservation, these studies showcase the advances in scientific research made possible by nanopore sequencing. Read on to stay on top of what's next.

Human Genetics

1. Benchmarking and quality control for nanopore sequencing and feasibility of rapid genomics in New Zealand: validation phase at a single quaternary hospital(medRxiv)

In this study, the team test the future potential of nanopore sequencing for scalable genomic testing for critically ill children in New Zealand. Utilising the PromethION 2 Solo, researchers achieved high precision and recall in identifying single nucleotide variants (SNVs) and small indels, and achieved 100% concordance with established clinical techniques. Nanopore technology facilitated a rapid turnaround time showcasing its future potential for broader application in acute care genomic diagnostics.

Key points:

• Nanopore sequencing enabled high precision and recall for SNVS and INDELS (see figure 1).
• The Oxford Nanopore platform accurately identified large genomic variations and haplotype-specific tandem repeats, essential for diagnosing neurodevelopmental disorders.
• The study demonstrated reliable detection of clinically relevant large chromosomal abnormalities at even low sequencing depths (~2X).
• Nanopore sequencing provided concurrent DNA methylation profiling with high concordance to bisulphite sequencing, offering comprehensive genetic insights.

Figure 1. Comparison of variant calling performance metrics in high confidence and coding regions.

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2. High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer (Nature Communications)

The study utilises long nanopore reads as part of Telo-seq, a method that resolves human telomere length and composition at high resolution. This technology enabled precise measurement of telomere maintenance mechanisms, revealing insights into aging and cancer mechanisms.

Key points:

• Telo-seq targets telomeres by annealing adapters to telomeres, and uses long nanopore reads to map and measure telomere lengths across different chromosomes.
• Telo-seq resolved bulk, chromosome arm-specific, and allele-specific telomere lengths, offering unprecedented detail.
• The method revealed how telomeres shorten with cell division and aging, providing insights into cellular senescence and crisis.
• Telo-seq distinguishes between telomerase-positive and ALT-positive cancer cells. Identifying these telomere maintenance mechanisms informs prognosis and treatment: telomerase-positive cancers may benefit from inhibitors, while ALT-positive cancers require different therapies. This enables personalized treatment, improving effectiveness and overcoming resistance.

Telo-seq is now available to researchers in early access - register your interest

3. Direct RNA sequencing of astronaut blood reveals spaceflight-associated m6A increases and hematopoietic transcriptional responses (Nature Communications)

Using nanopore direct RNA sequencing, researchers analysed blood samples from four SpaceX Inspiration4 astronauts, revealing significant spaceflight-associated changes in N6-methyladenosine (m6A) RNA methylation. This research provides comprehensive, single-nucleotide resolution insights into molecular responses to space travel, marking the first longitudinal RNA sequencing study of astronauts.

Key points:

• Enabled quantitative mapping of modification and expression changes at single-nucleotide resolution across entire isoforms.
• Analysed whole blood samples from four astronauts at seven time points, including pre-flight, return day, and post-flight recovery.
• First m6A methylation profiles for a human space mission, showing a significant spike in m6A levels immediately post-flight.
• Identified key genetic pathways altered by spaceflight, particularly in erythrocyte regulation, stress induction, and immune response.
• Provided the first longitudinal long-read RNA profiles and RNA modification maps for astronauts, enhancing understanding of the human transcriptome’s dynamic response to spaceflight.

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Animal Genetics

4. A high-quality Oxford Nanopore assembly of the hourglass dolphin (Sagmatias cruciger) genome (bioRxiv)

This study presents a high-quality genome assembly of the hourglass dolphin (Sagmatias cruciger) using Oxford Nanopore. This achievement marks a significant step in genomic research by providing a comprehensive genetic resource for this rare and poorly studied species, aiding conservation efforts and taxonomic clarity.

Key points:

• Using Oxford Nanopore-only (with the latest chemistries), the authors achieved a high-quality assembly with 98.3% BUSCO completeness (see Figure 2), proving that nanopore data alone can deliver uncompromised accuracy.
• The study showcases a cost-effective approach to mammalian genome assembly (no need for costly multi-platform approaches), making genomic data generation more accessible.
• The project emphasises the importance of upholding Indigenous data sovereignty, involving local communities in the research process.
• The assembled genome will facilitate insights into population size changes, adaptation, and the impact of climate change on the species.

Figure 2. IGV screenshot of phased haplotigs of the hourglass dolphin genome based on long Oxford Nanopore reads (10 Kbp scale), showing genome-wide phasing despite low polymorphism in some regions.

5. Metabarcoding for authentication of fish species in surimi-based products by nanopore sequencing (Food Bioscience​)

Using nanopore sequencing, researchers identified fish species in commercial surimi products, revealing significant mislabeling. This technology enabled the detection of 133 species across 20 products, highlighting both the potential for food fraud and the sustainability of current surimi production practices.

Key points:

• Surimi is a seafood product made from a variety of marine species, but overharvested, rare, or toxic species from illegal fisheries may be intentionally incorporated to increase economic profit. This practice raises significant sustainability issues, as it can lead to the depletion of vulnerable fish populations and disrupt marine ecosystems.
• DNA from surimi products was sequenced using the MinION device, with COI gene amplification.
• 133 fish species from 46 families were identified, with many mismatches between the product label and the genetically identified species, particularly in itoyori and mackerel products.
• The study demonstrated the effectiveness of nanopore sequencing in detecting food fraud and highlighted the unsustainable nature of surimi production when it includes endangered or illegally sourced species. This detailed identification of species helps in understanding the extent of mislabeling and the risk it poses to marine biodiversity and sustainability.

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Microbiology and Infectious Diseases

6. Detection of hidden antibiotic resistance through real-time genomics (Nature Communications)

Real-time genomics via nanopore sequencing significantly improves antibiotic resistance detection, as demonstrated in a multi-drug resistant Klebsiella pneumoniae case study. This approach identifies resistance mechanisms missed by conventional methods, enhancing clinical decision-making and patient outcomes.

Key points:

• Nanopore sequencing detected low-abundance plasmid-mediated resistance missed by conventional diagnostics, for example blaKPC-14 which explained resistance to Ceftazidime-Avibactam in this case study.
• Nanopore sequencing provided initial data within 1.5 hours, much faster than the 52 hours required by traditional methods, facilitating timely intervention.
• The detection of blaKPC-14 was done by conventional diagnostics, but the study shows that nanopore sequencing would have detected this much more rapidly. This timely detection would likely have led to more timely and effective intervention.
• “The fast, adaptive, and in situ nature of antibiotic resistance profiling by nanopore sequencing would have surpassed current clinical practice in accurately informing clinical management.”

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