Oxford Nanopore Technolo... Share Discussion Threads

[eeza] 12/12/2023 16:48

Groundhog day every day.

Un-investable until the Golden Share is discarded. That Golden Share makes shorting a risk-free trade.

New all-time lows looming large.

[bamboo2] 10/12/2023 14:53

Sellers outweighing buyers.

Aware of some lengthy negotiations going on in the background, I am anticipating news on a tie up with the NHS at some point soon. I originally thought there might be some sort of announcement at Houston.

The management team has been spending a lot of time in the US, and the co has taken on a large number of new people. Vacancies [Worldwide] are currently running at 96, up from 77 a few weeks ago.



I reckon we will soon see some kind of announcement on the future of the managements golden shares.

This will be good news to one of the institutions that has been quietly buying in the background, Norway based The Storebrand Group, as they have a dislike of anti-takeover set-ups.

[eeza] 09/12/2023 12:08

Not quite.

21 March 23 low was 169.60p.

But will probably drop below that next week. share price is losing an av of 4p per day atm.

[brucie5] 09/12/2023 11:53

At March 23 low.

[bamboo2] 09/12/2023 11:04

New Method Enables Long-Range Protein Sequencing Using Oxford Nanopore Platform
Dec 07, 2023 | H Zhang




NEW YORK – Researchers from the University of Washington have developed a new approach that promises to achieve long-range, single-molecule sequencing of intact protein strands using the commercially available platform from Oxford Nanopore Technologies.

Described in a BioRxiv preprint published in October, the proof-of-concept study, which was partially supported by Oxford Nanopore, opens the door for further potential proteomics applications on the company's sequencers.

"The big breakthrough with DNA and RNA [nanopore] sequencing was using the motor to pull the DNA and RNA strands through the pore," said Jeff Nivala, a molecular engineering professor at the University of Washington and the senior author of the study. "How you would do this for proteins was really the challenge."

According to Nivala, one major hurdle to nanopore sequencing of full-length proteins is that the molecules are typically heterogeneously charged, making it challenging to rely on the electrophoretic force to translocate the protein strands through the pores in a controllable fashion.

In addition, Nivala said his team sought to utilize the commercially available Oxford Nanopore devices given that "they are out of the box and ready to go." However, the challenge associated with that is the Oxford Nanopore flow cells do not allow users access to the trans side — opposite of protein loading — of the pore, where unfoldase motor proteins are normally deployed to facilitate protein translocation and sequencing.

To overcome these challenges, Nivala's team devised a two-step approach using the Oxford Nanopore MinIon device and R9.4 flow cell. First, the protein substrate is transported through the nanopore via electrophoretic force, while a blocking domain is affixed to the C-terminal of the protein to prevent the complete translocation of the molecule. Subsequently, ClpX — an ATP-powered protein unfoldase — is added to the cis side of the array to pull the analyte back out of the pore in a controllable fashion.

While the initial threading of the protein through the pore by electrophoretic force happens too fast to result in any reliable signals, Nivala said, the unfoldase-mediated translocation of proteins back out of the pore can produce slow, reproducible ionic current signals.

In addition, Nivala said the team has designed a "slippery" amino acid sequence near the N-terminal of the protein strand to allow the molecule to temporarily slip off the ClpX protein. This allows the analyte to thread through the pore again via electrophoretic force, followed by ClpX-mediated reverse translocation for repeated sequencing readout.

In their study, Nivala and collaborators used synthetic proteins to benchmark the performance of the method. Overall, the study showed single-amino acid reading sensitivity and demonstrated the capability to analyze all 20 different single-amino acid residues within synthetic analytes in a static background.

In addition, Nivala said the method illustrated its capability to process folded full-length protein strands over 100 amino acids in length, setting the stage for analyzing natural protein molecules using the approach.

Furthermore, the UW researchers built a biophysical model to help predict nanopore ionic current signals directly from protein sequences. This model would potentially enable a "lookup table" style of approach, similar to mass spectrometry, to help identify and fingerprint full-length, single-molecule proteins, the authors noted.

"I think this will be really important going forward for protein fingerprinting-type approaches," Nivala said. "If you know what the theoretical nanopore squiggles look like when [the samples] go through a nanopore, you can then identify the full-length protein based on that match to your model protein."

While other nanopore-based fingerprinting approaches or traditional mass spectrometry typically look at small peptides, a unique advantage of their model is that it can achieve analysis of full-length proteins, Nivala noted.

"It's a pretty impressive amount of work," said Liviu Movileanu, a professor at Syracuse University who was not involved in the study. "What is remarkable is that [the authors] went beyond just measuring the currents; they analyzed the signals and produced modeling … that in a sense can be expanded to [protein] fingerprinting in the future."

Such fingerprinting models can be potentially deployed for disease detection or biomarker profiling, Movileanu added.

Additionally, he applauded the authors' efforts to design a method using the commercially available Oxford Nanopore flow cells, which have already demonstrated "an amazing ability for high throughput" in DNA sequencing.

Furthermore, Movileanu said the analysis of the unfolding and translocation behaviors of different proteins by the unfoldase in the study also serves as a knowledgebase for the field to investigate and utilize the enzyme for further applications.

Despite the promises, Nivala noted that the method presented in the current paper is "not at the final version" and has some limitations. For one, he pointed out that the two-step flow cell loading process, where protein substrates and the unfoldase enzymes are loaded separately, can limit the throughput of data collection during each cycle.

To that end, he said the team is working to develop a workflow where the unfoldase can be prebound to the analyte and only become activated when the protein strand is captured in the pore, similar to the mechanism adopted in nanopore DNA sequencing.

Another potential limitation of the method is that a ligation step will be required to affix the synthetic N- and C-terminal sequences to the analyte when analyzing natural proteins, said Nivala.

Nivala said the near-term goal for the team is to continue enhancing the predictive models for protein fingerprinting by collecting more data on natural protein sequences.

In the long run, he said the goal is to eventually achieve single amino acid de novo sequencing using nanopores. "I think de novo sequencing of individual amino acids of natural proteins is still going to be a big challenge, and there are hurdles to go," Nivala said. "We're exploring different alternative pores that will help provide better resolution."

Nivala said UW has filed provisional patents covering aspects of this study, and there are "ongoing considerations" regarding potential commercialization plans of the method. In addition, Nivala noted that his team has an open collaboration with Oxford Nanopore, which partially supported the study. As such, "there are considerations that go along with that as far as the IP," he said.

An Oxford Nanopore spokesperson declined to comment on whether the company has any interest in commercializing the method described in the study or provide details on how the approach fits into the company's overall protein sequencing R&D.

"Protein sequencing compared to even RNA sequencing is still a baby," Nivala said. "It's still early days, but [it's] really exciting to see where it can go."

[bamboo2] 07/12/2023 19:55

This year’s report confirms the UK genomics sector as a global leader. It showcases where the use of genomic technologies is already having an impact on patient and public health and highlights emerging applications and growth opportunities.

Published today (7 December 2023) by the UK BioIndustry Association (BIA), the Wellcome Sanger Institute and Medicines Discovery Catapult (MDC), the Genomics Nation report showcases the role of genomics in the UK life sciences sector and its public health system.

[bamboo2] 07/12/2023 19:37

Oxford Nanopore tech starting to mature. [at last!]

Thu 7th December 2023

At NCM Houston, we heard scientists from the Nanopore Community across numerous fields share how they are utilising nanopore sequencing to revolutionise their research. Here, we dive into three great plenary presentations from the event.

[bamboo2] 07/12/2023 16:33

Oxford Nanopore Technologies plc

Nanopore Community Meeting Technology Update

7 December 2023

Oxford Nanopore Technologies plc (LSE: ONT) ("Oxford Nanopore"), the company delivering a new generation of nanopore-based molecular sensing technology, on Wednesday announced an R&D programme delivering a significant jump in platform performance to enable further scientific discovery, in addition to a springboard into clinical markets, as part of a broader technology update at its Nanopore Community Meeting in Houston.

Oxford Nanopore SVP of Product and Programme Management Rosemary Sinclair Dokos and SVP R&D Biologics Lakmal Jayasinghe detailed breakthrough performance in DNA/RNA nanopore sequencing, including new improvements in DNA sequencing accuracy - reaching a record of Q28 (99.8%) in median simplex single pass accuracy - powered by machine learning-guided enzyme engineering and improved models. They also detailed a novel method to overcome errors in homopolymer regions that, when combined with other platform updates, pushed human consensus accuracy up to Q50 and indel F1 accuracy to 99%.

Additional platform updates included significant improvements in direct RNA sequencing to support the emergence of RNA-based therapies as well as numerous research areas of RNA biology, including m6A modified base calling.

As Oxford Nanopore continues to expand its user community in clinical and industrial applied markets, the team also shared the latest on its locked down product platform, Q-line, and announced TurBOT beta access to deliver an optimised sample-to-result product, strengthening its collaboration with Tecan.

A replay of the presentation is available to view on the Oxford Nanopore website at:

[bamboo2] 07/12/2023 12:22

Oxford Nanopore gave an update in the US NCM meeting, which took place in Houston Texas, with some Work In Progress (WIP) on new developments in terms of chemistry, motors and software.

[bamboo2] 07/12/2023 07:52

Oxford Nanopore launches TurBOT beta access to deliver optimised sample-to-result product, strengthening collaboration with Tecan
Wed 6th December 2023

At the annual Nanopore Community Meeting in Houston, Oxford Nanopore will showcase progress in automation, integration and accessibility with end-to-end workflows.

Oxford Nanopore today announces the beta launch of its TurBOT sample-to-result device, developed in partnership with automation and manufacturing specialist Tecan, at its annual Nanopore Community Meeting in Houston. Beta access customers will receive their devices in in the first quarter 2024, with wider early access planned for summer 2024.

TurBOT is a benchtop solution designed to offer automated extraction, library preparation, sequencing, basecalling, and data analysis for multiple samples, all within a single device. TurBOT will enable users to perform a hands-free, simplified workflow from raw sample to analysis though an intuitive interface, eliminating manual interventions and enhancing efficiency, reducing errors, and significantly accelerating the workflow. This will not only increase throughput but also ensure reproducible and reliable results.

By collaborating with Tecan, Oxford Nanopore will draw on Tecan’s over 40 years of experience in original equipment manufacturing (OEM) to develop the benchtop solution with an integrated nanopore sequencer. This intuitive solution will allow scientists to start sequencing immediately, saving training effort and time.

The first fully automated end-to-end workflows will be compatible with the MinION for research use in bacterial microbiology and infectious diseases, followed by compatibility with the higher output P2Solo with workflows for human and cancer genomics research. This will bring streamlined, automated nanopore sequencing into the lab, enabling fully hands-off sequencing that is reliable and reproducible.

Oxford Nanopore’s technology generates information rich data including small variants, structural variants and methylation from a single experiment. This paired with the technology’s scalability and ability to deliver rapid results enables base-modification analysis to be performed alongside nucleotide sequencing on the same single read without the need to run multiple sequencing experiments. Therefore, unlike traditional technologies, such as, bisulfite sequencing, no additional complex library preparation is required, and epigenetic modification analysis can be performed across the whole genome during the experiment. Combining highly reproducible automated library preparation of short and/or long fragments and high outputs of genomic data makes it feasible to reliably identify a comprehensive map of genetic alterations, conduct accurate phasing, resolve repeated sequences, and measure DNA methylation, all in a single sequencing run.

Rosemary Sinclair Dokos, SVP, Product and Programme Management and Lakmal Jayasinghe, SVP R&D Biologics will give further product and pipeline updates at NCM. They will share news on integration of tertiary analysis, proof-of-concept improvements on homopolymers, increased accuracy.

Gordon Sanghera, CEO, Oxford Nanopore Technologies, commented:

“With TurBOT we are delighted to be able to offer our customers the ability to accelerate their genomics research with access to Oxford Nanopore's end-to-end workflows conveniently packaged into a single device. Tecan is the ideal partner for us, together with its extensive experience in bringing these solutions to market and our nanopore sequencing platform, we have created this intuitive solution that will save processing time, cost and deliver streamlined sequencing.”

Ralf Griebel, EVP, Head Partnering Business, Tecan, commented:

“At Tecan we are driven to improve people’s lives and health by scaling healthcare innovation globally. Our partnership with Oxford Nanopore is a perfect example of bringing our purpose to life. Building on our existing collaboration for high-throughput library preparation on our DreamPrep® NGS platform, the TurBOT sample-to-answer device will bring new levels of convenience and reliability to Oxford Nanopore’s customers and ultimately allow the information generated by nanopore sequencing to benefit more patients in areas such as infectious diseases and oncology.”

[74tom] 06/12/2023 10:18

Yep that's a fantastic article @Bamboo2. Especially like this last para;

"I see the same thing happening with Nanopore. It’s been a slow burn but they’re just at the precipice of changing everything. They have a platform that, in my opinion, is fundamentally better in virtually every way. They have an outside force pushing for a huge increase in attention on the underlying structure of the exhaust data coming off the sequencer (long-read > short-read). The more attention and focus GenAI and LLMs get in the genomics/pharmaceutical space, the more value will be perceived in their tech."

I think the CRISPR use cases are particularly exciting, I posted a link last month to the CRISPR Therapeutics FDA Adcom meeting in which a panel expert suggesting using ONT for the 15 year post approval monitoring study of off target edits. The data that ONT would garner as a result of such studies would fulfil the exact criteria that is discussed in that blog.

Here is another interesting link of Nvidia CEO Jensen Huang discussing the next 'amazing revolution' is going to come from; digital biology. 'Biology has the opportunity to be engineering not science'



Again, describes ONT to a tee. 'Once it becomes engineering it becomes less sporadic, and exponentially improving'...

[brucie5] 05/12/2023 11:17

bamboo22 Dec '23 - 09:31 - 1048 of 1054
0 1 0
Great article from US based Ryan Casey...
---------------------------------------------------------------------------------
That's amazing, Bamboo. Makes me want to take another look here.

[eeza] 05/12/2023 10:59

Yes, trading looks more like short-bots scalping small %ages. Even tiny rises of 2p are sold off.

[bamboo2] 05/12/2023 10:34

eeza, I follow actual daily volumes, including late trades.
Since 30/9/2023 there have been 8 sessions where volume has topped 2 million.
[btw 2 million is double the average daily volume]
The total excess trades over the 8 sessions is about 10.6m

The market has absorbed a huge amount of stock, which makes me think INOV is probably not the only seller.

[bamboo2] 04/12/2023 21:38

eeza, rebalancing could mean bringing their ONT holding down to a similar percentage as their next largest holding, which would mean a reduction of approx 50%

[eeza] 04/12/2023 21:04

Reduced by ~3m in 9 months.

So only another 4 years 'til they're out.

[bamboo2] 04/12/2023 19:47

Some detective work on the remainder of the Woodford holding [formerly the Woodford Patient Capital Trust holding] which is now managed by Schroders under the ticker INOV.

Nortrust Nominees Limited A/C WIZ02(7) Prior to admission 25,927,100 3.65%
Post admission 23,334,390 2.94%

Beneficial interest in these Ordinary Shares was held by Schroder UK Public Private Trust plc under the ticker SUPP, now known as INOV.

Day/mth/yr Holding value ONT share price quantity held

31/12/2022 £56,529,000 2.466 = 22,923,357
30/06/2023 £44,000,000 2.132 = 20,599,250
30/09/2023 £42,100,000 2.056 = 19,990,272

Therefore, at eod on 30/9/2023 INOV held 2.33%

They are committed to 'rebalancing' their portfolio, so I expect the selling to continue.

[bamboo2] 04/12/2023 18:59

Hand-held sequencing device may help track resistant-malaria in African hotspots
The software, being trialled in Ghana, could help identify mutations in the parasite that causes disease

Maeve Cullinan,
GLOBAL HEALTH SECURITY REPORTER
4 December 2023 • 3:05pm

“But, reality is that the [portable] technology still does better in addressing these challenges than any of the other major sequencing platforms. I have no doubt that it holds the keys to the future of pathogen surveillance in Africa,”

[bamboo2] 02/12/2023 09:31

Great article from US based Ryan Casey...


"...I see the same thing happening with Nanopore. It’s been a slow burn but they’re just at the precipice of changing everything. They have a platform that, in my opinion, is fundamentally better in virtually every way..."

h ttps://beyondyellowwoods.substack.com/p/the-genomics-war-illumina-nanopore

[bamboo2] 30/11/2023 17:28

eeza, yes quite a bit showing up after hours. About 5m so far.

7.00pm Up to 5.5m now

Could this be buyers getting ahead of short sellers, or shorts covering?

[eeza] 30/11/2023 09:21

Good volume, and battle between light & dark forces.

[bamboo2] 30/11/2023 07:50

Including this one and another in the UK, there are now at least half a dozen rare disease initiatives around the world using ONT kit.

=======================
30 November 2023

Oxford Nanopore Technologies plc

New genomic funding awarded in Australia to boost national rare disease research programme, using Oxford Nanopore Technologies

Oxford Nanopore Technologies plc (LSE: ONT) ("Oxford Nanopore"), the company delivering a new generation of nanopore-based molecular sensing technology, today announces that Oxford Nanopore technology will be used by Dr Ira Deveson in a three-year project at the Garvan Institute of Medical Research, establishing a national sequencing programme to address challenging unsolved cases and to improve the identification of the genetic cause of rare diseases. The project involves evaluating and optimising nanopore sequencing for prospective clinical use, as well as determining best practices for sample preparation, sequencing, and analysis to generate high-quality, reliable data.

By incorporating long nanopore sequencing reads into rare genetic disease characterisation, the researchers aim to raise future diagnostic rates, enabling more patients to receive accurate recognition and treatments. Identifying new variants and disease mechanisms may uncover new therapies for these conditions.

Standard gene tests analyse short segments of DNA before assembling them into a full sequence. This traditional method may miss large or complex genetic changes that can also cause disease. By leveraging Oxford Nanopore technology's ability to sequence any-length fragment of DNA, the researchers will gain a more comprehensive picture of the genome and will be able to detect complex genetic variants that traditional sequencing methods often miss.

Gordon Sanghera, CEO, Oxford Nanopore Technologies, commented:

"We are delighted for the team and congratulate the researchers on being awarded this important funding. It is great to see so much research being dedicated to rare genetic disorders and with nanopore sequencing data they will get much more comprehensive insights. What you're missing matters, so with Oxford Nanopore's ability to sequence any-length fragments of DNA we believe the team will be able to resolve significant blind spots and we look forward to hearing about their progress and discoveries."

Dr Ira Deveson, Head of the Genomic Technologies Lab at the Garvan Institute of Medical Research, commented:

"We believe new generation sequencing technologies will hold the key to unlocking some of the most challenging unsolved cases of rare genetic diseases, changing how we characterise and treat these conditions. Our national programme, involving nanopore sequencing, will not only increase the future overall diagnostic rate but also contribute to the discovery of new genetic variants and potential new treatment approaches for people with rare diseases."

The research team was awarded a grant from the Medical Research Future Fund Genomics Health Futures Mission. The full Garvan Institute of Medical Research announcement is available here...

[bamboo2] 29/11/2023 22:59

Hi papillon. ONT mkt cap...

Total shares 858,536,198 x 1.932 = £1,658,691,934.54

There are a number of reasons for the poor share price performance since IPO in OCT 2021. I am not sure there is much point in listing them!

The sector boomed during covid, and has since corrected.

[bamboo2] 29/11/2023 22:51

Quadram Institute Leads €1.1M Consortium Using Nanopore Sequencing for AMR Surveillance Nov 27, 2023

NEW YORK – The UK's Medical Research Council has provided €1.1 million ($1.2 million) for a new international research consortium to develop nanopore sequencing-based methods of detecting and monitoring the spread of antimicrobial resistance (AMR) in bacteria.

Alison Mather, a researcher at the UK's Quadram Institute and the University of East Anglia, will lead the Metagenome-Informed Antimicrobial Resistance Surveillance (MEGAISurv) project, joined by researchers from University College Dublin, Utrecht University, and Dawn Farm Foods.

The consortium aims to develop tools based on metagenomic sequencing to assess the level of AMR in a sample and the risk of its spread, as well as new analytical tools to investigate point mutations causing AMR in metagenomes and a novel computational framework to risk assess the spread of AMR.

"By applying these tools in real-world settings, we will learn how best to use them to target and evaluate interventions to reduce the spread of AMR," Nick Andrews of Dawn Farm Foods said in a statement.

The team plans to use long-read sequencing from Oxford Nanopore Technologies, which can also provide information about how transmissible a particular AMR gene is by detecting it within mobile genomic contexts such as plasmids and transposons.

MEGAISurv is the latest alliance for Quadram built around nanopore sequencing. For example, in 2022 it partnered with Eagle Genomics on microbiome research.

[papillon] 29/11/2023 20:40

Why the big drop in the share price since it listed just over 2 years ago, bamboo2?

advfn give the Mkt Cap as £1.65 billion. Is that correct?