Oxford Nanopore Technolo... Share Discussion Threads

[bamboo2] 11/4/2024 12:26

2 April 2024

An evolution of Nanopore next-generation sequencing technology: implications for medical microbiology and public health

Next-generation sequencing has evolved as a powerful tool, with applications that extend from diagnosis to public health surveillance and outbreak investigations. Short-read sequencing, using primarily Illumina chemistry, has been the prevailing approach. Single-molecule sensing and long-read sequencing using Oxford Nanopore Technologies (ONT) has witnessed a breakthrough in the evolution of the technology, performance, and applications in the past few years. In this issue of the Journal of Clinical Microbiology, Bogaerts et al. (hxxps://doi.org/10.1128/jcm.01576-23) describe the utility of the latest ONT sequencing technology, the R10.4.1, in bacterial outbreak investigations. The authors demonstrate that ONT R10.4.1 technology can be comparable to Illumina sequencing for single-nucleotide polymorphism-based phylogeny. The authors emphasize that the reproducibility between ONT and Illumina technologies could facilitate collaborations among laboratories utilizing different sequencing platforms for outbreak investigations.

[ih_828197] 11/4/2024 11:51

i just hope they don't get bought for cheap like 1-2B as i can see a future where they make that much in a quarter.

[ih_828197] 11/4/2024 11:48

i'll just keep averaging down or up if the price starts to pick up, like you said i don't see anything wrong fundamentally. If i were you i wouldn't worry too much about finding the perfect entry point as long as you have a long term view (5+ years)that of course changes if you are looking for a swing trade. Actually i'm happy to see the stock price going down means i can buy more for less. There are so many signs that point to nanopore having a clear technological advantage. It's just a question of execution.
I don't think people who bought AMD at 10$ are upset they dind't buy it at 7$ instead ahahah

[brucie5] 11/4/2024 08:35

Anyone else thinking of buying hereabouts? The decline feels curiously like gravitational pull towards £1. Maybe it will then test buyers by further weakening with 90p as base level? Obviously it won't be humble pis who move in to reverse the price, so I'm alert to any large insti buying.
We can't be too far away now and confidence seems to have completely evaporated.
In the meantime I can't see anything wrong with the story. Maybe the market is preparing it for an opportunistic TO?
Brexit Britain : everything bar the crown jewels for sale, and these look like being the jewels in their sector.

[magnum opus] 08/4/2024 08:59

Hard to believe share price now less than half what trade buyer Bio Meriuex paid (238p) back in Oct, mkt cap 950m cash 470m, would seem to be an ideal fit for them because they could sell the devices through their own sales force cutting costs, and use the devices potentially in a lot of new assay methods and approaches, roll on lat expiry in June

[brucie5] 03/4/2024 15:08

I'm waiting for aries to come under the influence of venus in the third solar quadrant of the planetry makeitupasyouwantittarium.
;)
In the absence of which, I might take £1.

[p1nkfish] 02/4/2024 19:31

I'm waiting to see a bullish engulfing candle at decent volume.

[brucie5] 02/4/2024 18:25

I'm waiting for £1.

[p1nkfish] 02/4/2024 09:03

Timing for reversal?

[p1nkfish] 02/4/2024 09:01

Yes, find out soon. Lots of shuffling going on. Possibly a bit of a relief bounce and some further consolidation before a reversal.

[bamboo2] 02/4/2024 07:52

p1nk, I guess we now get to see if the end of year tax loss idea will reduce the number of sellers?

[bamboo2] 29/3/2024 09:04

GIC Private Limited Singapore. Singapore SWF.

Reducing to less than 3%, below both international and UK [TR-1] reporting threshold.

Prior holding was 3.976561% or 34,177,560

=============

I note from INOV's figures to December 31 2023 released this week, that, to the reporting date, their piecemeal disposals of ONT shares had slowed. There didn't appear to be any update on their holding over the past three months of 2024.

[74tom] 28/3/2024 19:33

So in the 2 months since the start if Feb, GIC have disposed of ~8m shares. Fairly obvious why shares are trading at all time lows

[brucie5] 27/3/2024 09:59

Just another 20% to drop, by the looks of.
😏

[brucie5] 25/3/2024 16:38

Blimey. New low. Not far to go now?

[p1nkfish] 24/3/2024 10:42

Tax losses might be a thing too. Crystallising those for use elsewhere.

[bamboo2] 24/3/2024 10:37

Brucie, hope the share price stabilizes soon!

We have at least one seller, INOV, [with the dregs of the former Woodford Patient Capital holding] they report 28/3/2024, so we will get more idea of their position.

GIC, the sovereign wealth fund of Singapore, was also selling recently.
[02/02/2024 TR-1 reduced to 3.976561% or 34,177,560]

Unfortunately many of the international institutional holders are below the 5% reporting threshold, meaning it's hard to keep tabs.

Ironically, the larger holders of shares that were fighting to get their allotments during the flotation now seem content to sell at any price!

This is despite the fact that the intended growth led objectives of the flotation, such as increases in headcount, and accuracy improvements are nearing completion.

[brucie5] 23/3/2024 12:39

Bamboo thank you. I. for one, am most appreciative of your ongoing commentary and undoubted expertise here. It's far too complex for me to understand in any detail, so you help me to see the wood for the trees.

I am looking for a bottoming pattern of the kind I believe we are currently seeing at OXB; and I suspect it won't be until we descend to the £1 level like a plane coming down to land. There may be bumps but eventually I expect a round of applause from the passengers who remained seated.
;)

[bamboo2] 23/3/2024 12:01

Price action is far from ideal.

This is a weak sector at present. Hopefully it should change at some point, as massive expansion of sequencing around the world is forecast. The UK market is discounting many growth and tech stocks, and analysts have taken against ONT management and their attempts to be realistic in the face of unexpected problems, such as the ban on export of devices containing NVDA chips to China.

On the positive side, ONT has almost completed the planned increases of staff in technical, manufacturing and sales functions. Naturally, this should increase turnover. Accuracy continues to improve and customer sentiment is at all time highs. The new ASIC should get an airing in May 2024.

Management have so far made no attempt to extend the life of LAT shares that expire in June 2024, which means takeover potential could lift the valuation. There are a large number of organisations around the world that could currently buy the whole company for pocket money.

I find ONT one of the most exciting companies in the UK, and despite a losing position at present will continue to hold for the long term.

[takeiteasy] 23/3/2024 11:08

Brucie, not just ONT, this part of biotech is in a major downtrend..including the highest beta type stocks in the ARK genomics fund...hot happy 5 year charts at all :(

dyor etc

[brucie5] 23/3/2024 09:57

I think bamboo offers us understanding of the huge story developing at ONT, independent of the plunging share price It may or may not be a great investment. My feeling is, it will come very good, in time; though at this rate £1 might soon reached.

[minsky] 22/3/2024 16:53

x = ONT share price;
while x > 0 {
bamboo2 posts article about ONT success;
x = x-2;
}

[bamboo2] 22/3/2024 13:53

A new National Academies of Sciences, Engineering, and Medicine [NASEM] report calls for a focused, large-scale effort to accelerate technological innovation to harness the full potential of RNA modifications to address pressing societal challenges in health, agriculture, and beyond.

The report is available to read free online,


ONT are currently the leaders in the study of raw RNA. Pacb have a system, but like their other products, it relies on SBS which means the sample to be sequenced has to undergo treatment before processing. This treatment can add errors.

Chapter 5 contains considerable info on Nanopore.

[bamboo2] 22/3/2024 11:52

Wasatch Biolabs Bets on Nanopore Sequencing for Clinical Testing, Research Services

Mar 21, 2024 | Huanjia Zhang



NEW YORK – Wasatch Biolabs is eyeing to become a high-throughput nanopore sequencing service provider for both research and clinical customers, exclusively using platforms from Oxford Nanopore Technologies.

Last month, the Brigham Young University spinoff launched one of its first commercial offerings — a targeted DNA methylation sequencing service that is based on proprietary molecular enrichment technology developed by company cofounders Tim Jenkins and Jonathon Hill, who are both professors at BYU.

"We started this company roughly two and a half ago with the goal of creating a high-throughput lab based off nanopore [sequencing]," said Wasatch CEO Chad Pollard, another company cofounder who is also currently a Ph.D. student in Jenkins' lab.

The targeted DNA methylation sequencing service enables researchers and clinicians to analyze epigenetic signatures of samples while avoiding PCR amplification biases and harsh bisulfite conversion, he said.

Jenkins, who also serves as the company's VP of research and discovery, said the workflow involves a proprietary hybridization method to pull down genomic regions of interest, which are then sequenced using the Oxford Nanopore platform.

It can currently target about 2,000 regions of interest across the genome, which typically span 1 kb to 2 kb in length. While the company offers pre-designed probes, customers can also develop their own probes with the company.

After target enrichment, sequencing libraries are prepared using Oxford Nanopore Ligation Sequencing Kit V14 protocols, followed by sequencing.

The raw data are processed using Oxford Nanopore's standard pipeline for basecalling and methylation analysis, which can detect 5mC, 5hmC, and 6mA.

For research use, the per-sample list price for the service ranges from $266 to $2,525, depending on batch size, according to the company's website.

Unlike in the traditional bisulfite sequencing approach, samples don't undergo harsh chemical treatment, which can damage them, said Hill, who now serves as Wasatch's VP of science and technology. In addition, the method requires no PCR amplification, which can be prone to errors and biases.

Besides methylation information, the service also offers insights into ​​copy number variations (CNVs), structural variations (SVs), single nucleotide polymorphisms (SNPs), and indels, Hill added.

Compared with existing target selection schemes for nanopore sequencing, such as CRISPR-Cas9-mediated approaches or adaptive sampling, Hill said the company’s method leads to "much higher enrichment" — typically in the range of 400-fold to 2,300-fold.

One application of the company's methylation assay is infertility testing, Pollard said, where it can detect the presence or absence of certain rare sperm in a sample by looking for specific DNA methylation signals.

The firm is also developing an assay to capture epigenetic signatures of neuron-derived cell-free DNA in blood as a predictor for the early onset of neurodegenerative diseases, he noted.

In general, the company wants to apply its enrichment method "in any way that's clinically impactful," Jenkins said, such as to sequence difficult regions of the genome, including pseudogenes or areas with high GC contents. Pollard said the company is in discussions with Oxford Nanopore about potentially developing the technology into a kit.

In an email, an Oxford Nanopore spokesperson said there is no partnership between the company and Wasatch at this point. She did not comment on any potential interest in commercializing Wasatch's target enrichment method.

In order to be able to offer high-throughput nanopore sequencing as a clinical service, the company is currently building out a 20,000-square-foot CLIA lab in Salt Lake City.

Wasatch also plans to move its headquarters to Salt Lake City from its current location in Heber City, Utah, where it operates an R&D sequencing lab that also offers nanopore research sequencing services, such as whole-genome sequencing and RNA-seq.

Currently, Wasatch employs 12 full-time employees and plans to expand its workforce to 40 by the end of this year. It is completely privately owned, and the only ongoing relationship with BYU is a sponsored research agreement, under which the company helps fund relevant research projects within Jenkins' and Hill's labs.

The firm has licensed its founding technologies from BYU, according to Pollard, who noted that it is working on six other patents.

To date, Wasatch has raised $11 million in Series A funding, supported by its parent company Renew Biotechnologies, a biotech incubator.

While Wasatch is betting on nanopore sequencing for methylation analysis, other companies have also been making strides on alternatives to bisulfite sequencing, using short-read sequencing platforms.

New England Biolabs, for instance, recently launched the NEBNext Enzymatic 5hmC-seq kit that promises to detect 5hmC at single-base resolution. The kit follows the company’s existing NEBNext Enzymatic Methyl-seq (EM-seq) product, which can analyze both 5mC and 5hmC but does not distinguish between them. By subtracting E5hmC-seq data from EM-seq, researchers can now determine individual 5mC and 5hmC sites, according to the company.

Additionally, Cambridge, UK-based Biomodal also recently launched a new version of its epigenetic sequencing and sample prep kit that enables researchers to achieve single-base resolution sequencing of the four standard DNA bases, 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC) from the same DNA molecule and in the same workflow.

With limited benchmarking data publicly available, it remains to be seen how Wasatch's workflow will fare against other players in the space.

Still, with the data quality of nanopore sequencing continuing to improve, Wasatch management thinks the opportunity is ripe for the company to venture into the nanopore clinical sequencing service market, which is vastly untapped at this point.

"If we tried this a couple of years ago, it would not have been ready, and I think if we waited a couple more years, then others would have beat us to it," Hill said. "We're trying to catch that wave just right, where the technology is just getting to the point where it's ready for prime time."