Population genomics
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'... the single-instrument, T2T assembly recipes presented here open the exciting possibility of personalized human genomes ... in any country and potentially any institution in the world'
Koren, S. et al. bioRxiv (2024)
Get a complete picture of the human genome on a single platform
The advent of high-throughput next-generation sequencing technologies has driven the field of population genomics — the large-scale comparison of genomes within a population — however, the field has been fundamentally limited by the representation of such a small proportion of genetic diversity. Nanopore technology enables researchers to capture global human genomic diversity using sequencing reads of unrestricted length (up to 4 Mb). Any-length reads not only lead to the generation of gapless, reference-quality, telomere-to-telomere (T2T) genome assemblies in under-represented populations, but also to the generation of near-chromosome-level, population-representative pangenomes.
High-throughput nanopore sequencing enriches variant discovery in different populations across 1,000s to 10,000s samples by resolving and phasing single nucleotide variants (SNVs), structural variants (SVs), copy number variants (CNVs), repeats, and DNA methylation, even within complex genomic regions such as centromeres and segmental duplications — all on a single platform.
Featured content
Streamlined, high-throughput whole-genome nanopore sequencing
Discover how our end-to-end workflow for genome-wide analysis of genomic and epigenomic variants across a large cohort of human clinical research samples generates accurate SNV, SV, CNV, short tandem repeat, and methylation results in a single assay.
Population-scale nanopore sequencing to understand dementias
In this presentation, learn how researchers have used nanopore sequencing to develop an efficient and scalable wet lab and computational pipeline to analyse ~300 research samples to further understand the genetics of Alzheimer's disease and related dementias.
Recommended device for population genomics
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PromethION 24
Combining up to 24 independently addressable, high-capacity flow cells with powerful, integrated compute, PromethION 24 delivers flexible, on-demand access to terabases of ultra-rich sequencing data — ideal for comprehensive variant identification across large numbers of clinical research samples.
Technology comparison
Oxford Nanopore sequencing
Legacy short-read sequencing
Any read length (50 bp to >4 Mb)
Short read length (<300 bp)
- Generate complete, high-quality genomes with fewer contigs and simplify de novo assembly
- Resolve genomic regions inaccessible to short reads, including complex structural variants (SVs) and repeats
- Analyse long-range haplotypes, accurately phase single nucleotide variants (SNVs) and base modifications, and identify parent-of-origin effects
- Sequence short DNA fragments, such as amplicons and cell-free DNA (cfDNA)
- Sequence and quantify full-length transcripts to annotate genomes, fully characterise isoforms, and analyse gene expression — including at single-cell resolution
- Resolve mobile genetic elements — including plasmids and transposons — to generate critical genomic insights
- Enhance taxonomic resolution using full-length reads of informative loci, such as the entire 16S gene
- Assembly contiguity is reduced and complex computational analyses are required to infer results
- Complex genomic regions such as SVs and repeat elements typically cannot be sequenced in single reads (e.g. transposons, gene duplications, and prophage sequences)
- Transcript analysis is limited to gene-level expression data
- Important genetic information is missed
Direct sequencing of native DNA/RNA
Amplification required
- Eliminate amplification- and GC-bias, along with read length limitations, and access genomic regions that are difficult to amplify
- Detect epigenetic modifications, such as methylation, as standard — no additional, time-consuming sample prep required
- Create cost-effective, amplification-free, targeted panels with adaptive sampling to detect SVs, repeats, SNVs, and methylation in a single assay
- Amplification is often required and can introduce bias
- Base modifications are removed, necessitating additional sample prep, sequencing runs, and expense
- Uniformity of coverage is reduced, resulting in assembly gaps
Real-time data streaming
Fixed run time with bulk data delivery
- Analyse data as it is generated for immediate access to actionable results
- Stop sequencing when sufficient data is obtained — wash and reuse flow cell
- Combine real-time data streaming with intuitive, real-time EPI2ME data analysis workflows for deeper insights
- Time to result is increased
- Workflow errors cannot be identified until it is too late
- Additional complexities of handling large volumes of bulk data
Accessible and affordable sequencing
Constrained to centralised labs
- Sequence on demand with flexible end-to-end workflows that suit your throughput needs
- Sequence at sample source, even in the most extreme or remote environments, with the portable MinION device — minimise potential sample degradation caused by storage and shipping
- Scale up with modular GridION and PromethION devices — suitable for high-output, high-throughput sequencing to generate ultra-rich data
- Sequence as and when needed using low-cost, independently addressable flow cells — no sample batching needed
- Use sample barcodes to multiplex samples on a single flow cell
- Bulky, expensive devices that require substantial site infrastructure — use is restricted to well-resourced, centralised locations, limiting global accessibility
- High sample batching is required for optimal efficiency, delaying time to results
Streamlined, automatable workflows
Laborious workflows
- Prepare samples in as little as 10 minutes, including multiplexing
- Use end-to-end whole-genome, metagenomic, targeted (including 16S barcoding), direct RNA and cDNA sequencing workflows
- Scale and automate your workflows to suit your sequencing needs
- Perform real-time enrichment of single targets or panels without additional wet-lab prep by using adaptive sampling
- Lengthy sample prep is required
- Long sequencing run times
- Workflow efficiency is reduced, and time to result is increased
