Cancer research and sequencing
The genetic underpinnings of cancer are diverse and many types of genomic aberration — from SNVs to SVs, fusion transcripts, and epigenetic modifications (e.g. DNA/RNA methylation) — can cause, contribute to, or indicate disease. As a result, researchers traditionally relied on multiple techniques to identify and analyse different forms of cancer. Now, through the facility to generate sequencing reads of any length, including ultra-long reads in excess of 4 Mb that can span complex genomic regions, combined with integrated base modification detection and real-time results, nanopore sequencing delivers a streamlined and rapid solution for complete characterisation of cancer samples.
Nanopore sequencing: the most comprehensive insight into cancer genomes
Without nanopore sequencing, our work wouldn’t be possible
Alberto Magi, University of Florence, Italy
Oxford Nanopore sequencing
Traditional short-read technologies
Unrestricted read length (>4 Mb shown)
- Comprehensively identify genomic aberrations, including those in complex and repetitive regions, from blood, tissue (inc. FFPE), and circulating tumour samples
- Accurately identify and phase single nucleotide variants, structural variants, and base modifications in a single sequencing assay
- Fully characterise splice variation and fusion transcripts — up to single-cell resolution
Read length typically 50–300 bp
Short reads do not typically span entire structural variants, repeat-rich regions, or full-length transcripts — requiring the use of complex computational analyses to infer results rather than direct identification. As a result, many important disease variants may be missed.
Direct, amplification-free protocols
- Detect and phase epigenetic modifications as standard — no additional prep required
- Eliminate amplification- and GC-bias
- Create cost-effective targeted cancer panels allowing analysis of SVs, SNVs, and DNA methylation using adaptive sampling or CRISPR/Cas9-based enrichment
Amplification required
Amplification can introduce bias — reducing uniformity of coverage with the potential for coverage gaps — and removes base modifications (e.g. DNA methylation) that have been shown to be associated with cancer risk, progression, and treatment outcomes, necessitating additional sample prep, sequencing runs, and expense.
Real-time data streaming
- Analyse data as it is generated for immediate access to results
- Perform flexible, on-device enrichment of single targets or panels, with no additional sample prep, 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 sequence data.
Flexible and on-demand
- Scale to suit your cancer sequencing requirements
- Get started with MinION at just $1,000, including flow cells and sequencing reagents
- Cost-effectively run targeted cancer panels using Flongle Flow Cells at $90 each
- Perform comprehensive whole-genome or transcriptome analyses and scale up sample throughput with GridION and PromethION devices
- Sequence as and when required using low-cost, independently addressable flow cells — no sample batching needed
Limited flexibility
Sample batching often required for optimal efficiency, potentially leading to long turnaround times. Traditional high-throughput benchtop sequencing devices require significant infrastructure requirements and expense — confining their use to well-resourced, centralised locations.
Streamlined workflows
- Prepare DNA samples for sequencing in as little as 10 minutes, including multiplexing
- Use whole-genome, targeted, and full-length RNA sequencing approaches
- Automated sample prep and streamlined sequencing
Laborious workflows
Typically, lengthy sample preparation requirements and long sequencing run times, reducing workflow efficiency and increasing turnaround times.
Accelerating cancer research through comprehensive genomic analysis
The facility to generate sequencing reads of any length — from short to in excess of 4 Mb — combined with simultaneous base modification identification (e.g. DNA or RNA methylation) and real-time analysis is providing new and actionable insights into the genomic causes and implications of cancer. Discover how researchers are using nanopore sequencing for comprehensive characterisation of cancer samples, delivering accurate and rapid analysis of SVs, SNVs, methylation, fusion transcripts, and splice variants — all from a single technology.
Get more cancer research content in our Resource centre, including videos and publications on analysing cell-free DNA (cfDNA) from liquid biopsies.
The potential of nanopore sequencing for personalised oncogenomics
At London Calling 2023, Kieran O’Neill (Michael Smith Genome Sciences Centre, Canada) shared work from the Personalized Oncogenomics Program research trial. Motivated by the wide range of tumour-specific variation that can be captured within a single sequencing assay using nanopore sequencing, Kieran described how they have ‘recalled all known clinically relevant fusions and structural variants not identified from short-read data’.
Faster analysis of cancer-associated variants using a unique targeted nanopore sequencing approach
Nakamura et al. (2023) applied adaptive sampling, an on-device target enrichment method unique to Oxford Nanopore, to enrich for putative pathogenic SVs in blood cancer research samples. In the same sequencing run, they were also able to directly detect methylation status. Long nanopore sequencing reads identified complex SVs, including mobile insertion elements which are ‘notoriously difficult to detect using short-read sequencing platforms’. In a separate study, Filser et al. (2023) also used adaptive sampling to rapidly resolve an SV of previously unknown significance in BRCA1.
An important advantage of [nanopore sequencing] is that epigenetics modifications such as methylation can be obtained for each sequence read and position’
Nakamura et al. medRxiv (2023)
Single-cell, long-read targeted sequencing reveals transcriptional variation in ovarian cancer
Single-cell transcriptome sequencing is a powerful tool for high-resolution analysis of gene expression in individual cells. However, traditional short-read sequencing approaches only allow sequencing of a small region at one end of the transcript. As a result, information crucial for an in-depth understanding of cell-to-cell heterogeneity is lost. Describing short-read sequencing as ‘inadequate for comprehensive characterisation of RNA isoforms’, Bryne et al. (2023) used long nanopore sequencing reads to develop Single-cell Targeted Isoform Long-Read Sequencing (scTaILoR-seq), a hybridisation capture method which targets over a thousand genes of interest.
The use of nanopore sequencing for epigenetic characterisation of cell-free DNA
At the NCM2022, Billy Lau (Stanford University School of Medicine, USA) presented his work using nanopore sequencing to characterise the methylation profiles of cell-free DNA (cfDNA) samples. He reported on a strategy developed by his team utilising single-molecule nanopore sequencing of cfDNA methylomes for the characterisation of cancer development.
Scalable sequencing for cancer research
Nanopore sequencing is uniquely scalable — from portable Flongle and MinION devices to the high-throughput benchtop GridION and PromethION platforms, there’s a nanopore sequencing device to suit your specific cancer research requirements.
* Theoretical max output (TMO). Assumes system is run for 72 hours (or 16 hours for Flongle) at 420 bases / second. Actual output varies according to library type, run conditions, etc. TMO noted may not be available for all applications or all chemistries.
† PromethION P2 and P2 Solo devices are currently preorder, with Early Access devices expected to ship in 2022.
PromethION
PromethION Flow Cells offer the highest yield for nanopore sequencing, translating into high coverage of human and cancer genomes or the very highest read count for full-length transcripts. With a range of devices available to satisfy all throughput needs, PromethION is ideal for comprehensive whole-genome characterisation and biomarker discovery across any number of cancer samples.
The highest throughput nanopore sequencing device, capable of running up to 48 independent, high-capacity flow cells — ideal for large, population-scale cancer research studies.
Genomic and transcriptomic sequencing using up to 24 independent, high-capacity flow cells — for complete characterisation of large numbers of cancer research samples.
Offering two independent PromethION Flow Cells for low-cost access to high-output sequencing – ideal for smaller sample number cancer genome and transcriptome projects. Available to preorder now.
From gene expression analysis to high-throughput targeted mutation detection, run multiple experiments on demand using five independent MinION or Flongle Flow Cells.
Adapting MinION and GridION for smaller, rapid tests and analyses, on single-use flow cells; ideal for rapid, low-plex, low-cost targeted cancer panels and library quality control.
Portable nanopore sequencing device — suitable for low-pass whole genomes, targeted panels, exome sequencing, and gene expression studies.
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