Applications Research areas
The advent of high-throughput genomic analysis technologies has driven the field of population genomics — the large-scale comparison of genomes within a population. Population genomics has been fundamental to the identification of novel variation that can define specific phenotypes, such as disease susceptibility; however, the technical limitations of traditional analysis platforms may miss important sources of genomic variation. Combining long sequencing reads (up to 4 Mb) with high sample throughput (up to 14 Tb on PromethION*) nanopore technology makes it possible to generate highly contiguous genomes, with resolution and phasing of single nucleotide variants (SNVs), structural variants (SVs), repeats, and DNA methylation in a single assay — across 10’s to 1,000’s of samples.
Long read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits
We identified over 22,636 SVs per individual, three to five times more than found with short-read sequencing data Beyter et al. bioRxiv 848366 (2021)
Oxford Nanopore sequencing
Traditional short-read technologies
Comprehensive genomic characterisation
- Long and ultra-long reads (up to 4 Mb) allow complete resolution of complex genomic aberrations
- Accurately identify and phase single nucleotide variants, structural variants, and base modifications in a single sequencing assay
- Generate and compare highly accurate genomes, and correct existing reference genomes
Limited genomic characterisation
Short sequencing reads do not typically span important classes of genomic aberrations such as large structural variants and repeat regions, instead relying on indirect inference and/or complex computational analyses for their detection. The requirement of traditional sequencing technologies for amplification can also introduce sequence bias and removes base modifications. As a result, only a fraction of the genomic variation present in a sample may be identified.
Flexible and on demand
- Scalable, affordable devices to suit all genome and project sizes
- Generate terabases of data with PromethION — use up to 48 high-capacity flow cells simultaneously or independently to match your sample availability and lab requirements
- Sequence smaller genomes at high throughput or perform low-pass sequencing of larger genomes with GridION
- Discover the advantages of nanopore sequencing and undertake pilot projects with MinION, at just $1,000, including flow cells and sequencing reagents
- Perform sample QC prior to large-scale studies using Flongle, with flow cells at $90 each
Traditional high-throughput benchtop sequencing devices require significant infrastructure requirements and expense — confining their use to well-resourced, centralised locations. Sample batching is often required for optimal efficiency, potentially leading to long turnaround times.
- Prepare DNA samples for sequencing in as little as 10 minutes, including multiplexing
- Easy-to-automate sample preparation kits and protocols suitable for large-scale population genomics projects
- Low DNA input requirements
- Run multiple analyses — whole genome, targeted, and full-length RNA sequencing — on a single device and at the same time, with modular PromethION and GridION
Typically, lengthy sample preparation requirements and long sequencing run times, reducing workflow efficiency and increasing turnaround times.
Real-time data streaming
- Analyse data as it is generated for immediate insights
- Gain enhanced coverage of specific genomic regions with real-time targeted sequencing using adaptive sampling
- Stop sequencing when sufficient data generated — wash and reuse flow cell
Fixed run time with bulk data delivery
Increased time-to-result and inability to identify workflow errors until it’s too late, plus additional practical complexities of handling large volumes of bulk sequence data.
New insights into large genomes
Discover how researchers worldwide are utilising long nanopore sequencing reads to support the generation of highly accurate and contiguous, chromosome-level genome assemblies across many different species. With the facility to generate read lengths in excess of 4 Mb, nanopore sequencing reads enable complete resolution of challenging genomic regions, allowing identification of previously hidden genomic variation — providing new insights into evolution and disease association.
Find more publications on the use of nanopore sequencing for large-scale population genomics studies in our Resource centre.
Structural variants and their impact on phenotypes, diseases, and population adaptation
In pursuit of a more comprehensive genomic characterisation of the Chinese population, Wu et al. performed a large-scale analysis of 405 individuals using long nanopore sequencing reads delivered by the high-throughput PromethION device. The team identified 132,312 structural variants (SVs), of which 53% were novel. Furthermore, they identified new SV associations with phenotypes and disease, including body height and anaemia.
‘Our study reveals the complex landscape of human SVs in unprecedented detail and provides new insights into their roles contributing to phenotypes, diseases and evolution’Wu, Z. et al. bioRxiv 430378 (2021).
Closing the gaps in the human genome
Almost 20 years after the first draft of the human genome was declared complete, there are still large regions (up to 8% of the genome) that remain elusive to analysis using traditional sequencing technologies. To finally deliver upon the promise of human genomics and personalised medicine, researchers and consortia, such as the Telomore-to-Telomere (T2T) consortium, are utlising long nanopore sequencing reads to complete human genomes, spanning important, highly repetitive regions such as centromeres and telomeres, plus large structural variants. To date, the T2T consortium has delivered complete, gapless assemblies and novel functional insights into human chromosomes X and 8 — including comprehensive analysis of DNA methylation alongside nucleotide sequence.
‘finishing the entire human genome is now within reach’Miga et al. Nature 585 (2020).
Scalable sequencing for population genomics
Nanopore sequencing is uniquely scalable — from portable Flongle and MinION devices, ideal for sample QC and pilot studies, through to the high-throughput benchtop GridION and PromethION platforms, which offer rapid and affordable access to the high yields of high-quality data required for large-scale population genomics projects.
Offering up to 24 independent, high-capacity flow cells with integrated compute, PromethION 24 provides flexible, cost-effective access to terrabases of sequencing data – enabling high-throughput comparative analysis of large genomes.View product
Running up to 5 independent MinION (or Flongle) Flow Cells, GridION enables flexible, high-throughput sequencing of smaller genomes and low-pass analysis of larger (eg. human) genomes.View product
Portable nanopore sequencing device — suitable for low-pass whole genomes and pilot population genomics studies.View product
The all-in-one sequencer. Get all the benefits of the original MinION device but with integrated high-resolution touchscreen, built-in compute, and complete connectivity.View product
Adapting MinION and GridION for smaller, rapid tests and analyses – ideal for low-cost sample QC prior to large population-scale analyses.View product
Automated sample extraction and library preparation.View product