Oxford Nanopore at ASHG 2022: One sequencing platform for all your biology, bringing access to human genomic information to anyone, anywhere

At this year’s American Society for Human Genetics meeting, Oxford Nanopore provided updates to the genomics community on the latest sequencing developments and the newest sequencing technology, the PromethION 2 Solo.

Throughout this year’s ASHG conference there were many opportunities to see the technology in action and to meet the team. Here we summarise the key Oxford Nanopore events and showcase how our teams demonstrated that by using Oxford Nanopore sequencing technology, it is now possible to resolve variants and epigenetic modifications across the entire genome, target large panels or single genes without PCR, and detect known and novel full-length transcripts — up to single-cell resolution. All your biology on one platform.

This meeting also provided the opportunity to see Oxford Nanopore’s latest device, the PromethION 2 Solo (P2 Solo). The compact P2 Solo device brings the benefits of high-coverage, real-time nanopore sequencing to every lab. Offering the flexibility of two independent, high-output PromethION Flow Cells, each capable of delivering up to 290 Gb of data, these devices enable low-cost, high-depth, high-accuracy DNA/RNA sequencing across multiple experiments and users.

Unravelling complex human genomes – one sequencing platform for all your biology

During this lunch seminar, scientists using Oxford Nanopore’s technology discussed how they have used it to interrogate the intricacies of the human genome, including previously inaccessible structural, methylated, and phased variants.

Danny Miller, Assistant Professor, University of Washington and Seattle Children's Hospital, Seattle, WA

• Danny discussed how long nanopore sequencing reads can be used to evaluate individuals with suspected genetic disorders. He highlighted that long nanopore sequencing reads enable single nucleotide variants (SNVs), insertions and deletions (indels), structural variants (SVs), and methylation to be called and phased from a single data source

• Long nanopore sequencing reads can shorten the time taken to characterise a disease and can increase the rate of detection of diseases; a traditional genetic workup currently is only successful in 50% of cases

• He then went on to show how long nanopore sequencing reads were used to identify a novel disease-causing nonsense variant in the SLC39A4 gene

• Danny ended by demonstrating how Oxford Nanopore’s sequencing technology was used to characterise inheritance of specific familial variants in under three hours from birth. You can read more here.

Fritz Sedlazeck, Associate Professor, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX; Department of Computer Science, Rice University, Houston, TX

• Fritz opened by talking about the value of structural variant (SV) detection and utility of long nanopore sequencing reads for resolving SVs

• He showcased the capability of the Sniffles2 SW for the curation of medically relevant genes by improving SV calling

• He highlighted the GREGoR consortium as well as the All of Us (AoU) program as two large-scale initiatives using long nanopore sequencing read data for research and discovery and how Baylor will be sequencing 1000 AoU samples with nanopore sequencing

• He ended by showing single-cell data on nanopore sequencing allows for a new level of resolution and SV and SNV detection.

Carolyn A. Morrison, Applications Scientist, 10x Genomics

• In her talk, Carolyn discussed alternative transcript isoform detection with single-cell and spatial resolution

• Oxford Nanopore sequencing is compatible with 10x Genomics' Chromium Single-Cell 3’, Single-Cell 5’, and Visium Spatial Gene Expression assays

• Cell barcoding and UMI assignments can be resolved with Oxford Nanopore data alone

• Full-length reads allow clustering by isoform expression and detection of alternative transcripts at single-cell resolution.

To conclude the session Rosemary Sinclair Dokos, SVP, Product and Programme Management, shared how the latest technological advancements in nanopore sequencing enable high-accuracy sequencing of genetic variation at all read lengths, all on one multiomics platform.

The sequencing platform for multiomics – where will Oxford Nanopore’s PromethION take you?

In this first CoLab, Brian Fritz, Senior Director, Product Management and James Brayer, Director, Field Product Management, at Oxford Nanopore shared how you can amplify your biological discovery with one scalable sequencing platform – from small projects to population scale initiatives. The session also covered:

• How nanopore sequencing enables high-accuracy variant detection, built-in methylation, long-read single-cell transcriptomics, and it matches, or exceeds, current industry data output and quality

• PromethION offers scaled solutions: all of the PromethION devices fit on the bench, at low or no capital expense

• Unmatched breadth of multiomics applications: DNA, RNA, base modifications, all read lengths, and more

• Nanopore sequencing’s continuous innovation towards our vision of enabling the analysis of anything, by anyone, anywhere

• Building on the multiomics capability of our platform Oxford Nanopore offers researchers the opportunity to incorporate SNP, SV, methylation and variant phasing across the genome - this provides deeper insights in a single experiment

• Oxford Nanopore now also has a fully supported workflow for single-cell transcriptomics. This has been established in collaboration with 10x Genomics and so far 90-130M reads on a single PromethION Flow Cell have been achieved.

It takes two — haplotype-specific identification of genetic and epigenetic variation using nanopore sequencing

In this CoLab presentation, Philipp Rescheneder, Director, Genomic Applications Bioinformatics, shared how long nanopore sequencing reads can be used to accurately identify genetic and epigenetic variation using a single dataset and illustrate the importance of assigning variants to the correct haplotype through phasing. Philipp also discussed how:

• One experiment enables discovery and haplotyping of genetic, and epigenetic variation

• Adaptive sampling is an efficient way to conduct methylation profiling across the human genome

• Combination of phasing and modification calling enables parent-of-origin assignments without trio sequencing.

• Nanopore data enables assessment of haplotype-specific large-scale changes as well as base pair-resolution calling of genetic and epi-genetic variation in cancer.

We are sharing Philipp's talk from ASHG as a Knowledge Exchange on 22nd November at 3pm (UK time).

Register here