Clive Brown: Technology update: The Knights who say Me

TL;DR

This talk provides an update on the latest developments in Nanopore technology, including improved chemistry, base calling algorithms, and applications in liquid biopsy.

Transcript

decided to give this talk really it's a mezzanine update if you want to call it that between the last major one we did and the london calling conference which is coming up in uh may and there are some good reasons for doing an intermediate update is because we are actually in the process of releasing quite a lot of new stuff immediately in fact bec... Read More

Key Insights

• 🚀 Nanopore is planning an intermediate update to keep customers informed about new releases and developments in their products and technology.
• 🔬 Progress in nanopore sequencing has come from software development and the use of machine learning techniques, resulting in high-fidelity signal and improved accuracy.
• 🔎 Nanopore has introduced the Q20+ chemistry (Kit 12) and upgraded motor (R10.4) to improve accuracy and performance compared to older versions (e.g., Kit 10 with R9.1).
• 📊 Nanopore is expanding the ways it reports accuracy by incorporating percentage of bases above certain confidence levels and calibrating quality scores per base. The goal is to provide more meaningful and precise measurements.
• 🔬 Nanopore is actively working on base modification calling, and their methylation calling is surpassing bisulfite sequencing in terms of accuracy. They are developing new tools and integrating them into their base callers for easier access.
• 📉 Nanopore is developing a feature called adaptive sampling, which allows users to target specific regions of interest and improve enrichment for longer molecules.
• 💻 Nanopore is working on a new base caller framework called Dorado, which will replace Guppy. The new framework is expected to be faster and will be compatible with Apple Silicon, allowing for more efficient data processing.
• 💡 Nanopore is exploring applications for short fragment mode, including liquid biopsy for cell-free DNA analysis. Early results show promising performance in detecting modifications and providing methylation profiles.

Questions & Answers

Q: How has software development and machine learning contributed to the improvements in Nanopore sequencing?

Software development and machine learning have played a crucial role in enhancing the nanopore signal, leading to high-fidelity sequences. By utilizing state-of-the-art machine learning methods, Nanopore has optimized base calling algorithms, resulting in improved accuracy and reduced error rates.

Q: What are the key features of the Q20 plus chemistry and its impact on sequencing performance?

The Q20 plus chemistry offers high accuracy with an error rate of less than 1%. It utilizes the R10.4 nanopore and e8.2 motor, resulting in a sharper signal and improved fidelity. The Q20 plus chemistry also allows for higher throughput, with speeds of up to 420 bases per second, making it more efficient for sequencing applications.

Q: How has Nanopore technology advanced in base modification calling, specifically in methylation detection?

Nanopore has made significant progress in base modification calling, surpassing traditional methods like bisulfite sequencing in methylation detection. Through the development of Remora, a standalone post-base calling re-base caller, Nanopore can accurately detect methylated and hydroxymethylated bases. The technology has been validated and is continuously being improved to achieve better methylation calling accuracy.

Q: Can Nanopore technology be applied to liquid biopsies, and what are the potential advantages?

Yes, Nanopore technology can be applied to liquid biopsies. By sequencing natural DNA without the need for amplification, Nanopore can detect modified bases on short cell-free DNA fragments. This approach allows for whole genome methylation scanning, identification of disease states, and tissue of origin determination. The ability to scan millions of CpG sites offers a more comprehensive analysis compared to traditional platforms.

Q: What are the upcoming developments and timelines for Nanopore technology?

The upcoming developments include the release of Kit 14, which features improved chemistry and flow cells, as well as the integration of modified base calling into the standard base callers. Adaptive sampling will be available on both GridION and PromethION instruments, and the release of PT Solo, a compact device, is expected in the near future. Additionally, London Calling, a hybrid event, is scheduled to showcase new advancements in Nanopore technology.

Summary & Key Takeaways

• Nanopore signal is enhanced through software development and machine learning methods, leading to high-fidelity sequences with low error rates.

• The latest chemistry, known as Q20 plus, offers improved accuracy and throughput compared to its predecessors.

• Base modification capabilities have been improved, allowing for better methylation calling and identification of rare mutations.