Oxford Nanopore Technolo... Share Discussion Threads

[bamboo2] 11/11/2021 22:20

Can PI's access broker notes? I don't know.

Citi are the only one out of six that have said "Hold" rather than "Buy". The small section that I have seen on twitter quotes a few possible headwinds.

1/ Higher accuracy comes at a higher price. The broker suggests that re reading the same dna more than once increases accuracy, but this comes at a greater cost.
I am quite certain this is not the case, although I lack the terminology and scientific skills to be able to describe precisely why. I am thinking along the lines of new flowcells and base calling software, engineering improvements at zero extra cost.
In fact, I reckon that in the case of ONT tech, we are without doubt witnessing a DNA sequencing version of Moores law. This view is widely accepted, and Citi's broker is barking [up the wrong tree] on this point.

2/ Component shortages. I recently heard Gordon Sanghera describe how they had used the strong cash position to build inventory way ahead of forecasted needs. Talking along the lines that there was little point building state of the art production lines if the store room was empty.

3/ limited visibility on S3 revenue [larger customers]. The broker says S3 revenue will be lumpy. That's not the case with the recent order from G42, it is spaced over three years. There appears to plenty of time to get organised, and satisfy the needs of G42. I presume that other large orders will also be serviced on an ongoing basis to mutual benefit. eg Genomics England.

The Citi broker could be right, but I have a strong feeling that he has not done his homework as well as I have.

===========================
13/11/2021 edit added, For info, I noted a few other comments about Citi's view on twitter.

On 11 Nov Ola Wallerman said,

"I suppose these are reasonable concerns, but for 1) one would think ONT could increase the numbers of pores/$ in a not too distant future if needed and for 2) solutions from NEB, Qiagen and FireMonkey are probably more automation-friendly already."

[bamboo2] 11/11/2021 21:15

tonsil, it hasn't taken very long for the community to catch on!

This is a preprint, so not yet peer reviewed. [But it will be]

Oxford Nanopore R10.4 long-read sequencing enables near-perfect bacterial genomes from pure cultures and metagenomes without short-read or reference polishing



Posted November 10, 2021

"Long-read Oxford Nanopore sequencing has democratized microbial genome sequencing and enables the recovery of highly contiguous microbial genomes from isolates or metagenomes. However, to obtain near-perfect genomes it has been necessary to include short-read polishing to correct insertions and deletions derived from homopolymer regions. Here, we show that Oxford Nanopore R10.4 can be used to generate near-perfect microbial genomes from isolates or metagenomes without short-read or reference polishing."

[bamboo2] 10/11/2021 22:52

These are either very near term target prices, or the analysts just do not understand the company.

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JPMORGAN STARTS OXFORD NANOPORE TECHNOLOGIES WITH 'OVERWEIGHT' - PRICE TARGET 725 PENCE

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RBC STARTS OXFORD NANOPORE WITH 'OUTPERFORM' - PRICE TARGET 800 PENCE

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BERENBERG STARTS OXFORD NANOPORE WITH 'BUY' - PRICE TARGET 662 PENCE

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BARCLAYS INITIATES OXFORD NANOPORE WITH 'OVERWEIGHT' - TARGET 700 PENCE

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[tonsil] 10/11/2021 11:32

Your posts are always worth reading. Great historical perspective here in your latest post.

[bamboo2] 09/11/2021 16:10

How do you stop outbreaks becoming epidemics in real time?


[use link for full text of press release]

Birmingham researchers placed genomic sequencing at the heart of the Ebola and Zika outbreak response.

By Professor Nick Loman

University of Birmingham

“Two decades ago, the publication of the first bacterial genome sequence, from Haemophilus influenzae, shook the world of bacteriology. Since then we’ve seen a complete transformation of our understanding of how bacteria function, evolve and interact with each other, with their hosts, and with their surroundings. Now we are able to sequence the entire genetic code of a disease-causing microbe or pathogen. The third decade promises to be just as exciting.”

Since that first genome sequence, three ‘revolutions’ have shaped the direction of progress: whole-genome shotgun sequencing, high-throughput sequencing and single-molecule long-read sequencing.

The powerful combination of genome sequencing and bioinformatics-driven analysis of sequence data has seen projects that used to take years and cost hundreds of thousands of dollars now being completed in a few days for less than the price of a meal out for two.

“I fully expect the gold rush to continue and to see the $1,000 human genome matched by the $1 bacterial genome. I think we’ll see a 'sequencing singularity', whereby sequencing becomes the method of choice for as-yet unthinkable applications. They have already managed the encoding and then sequencing Shakespeare's sonnets in a DNA format, there are so many directions this could take.”

Indeed, the benefit of the advances is already being felt in very real terms.

In April 2015, Professor Loman’s PhD student, Josh Quick, arrived in Conakry, Guinea.

The Ebola outbreak in West Africa was the deadliest occurrence of the disease since its discovery in 1976. Since the first confirmed case was recorded on 23 March 2014, over 11,000 people died as the result of the virus. Despite a coordinated international response to the outbreak, it proved extremely difficult to control.

The ambition was to deploy a portable “laboratory in a suitcase”, allowing for Ebola samples from patients to be sequenced as soon as new cases were diagnosed. With less than 50kg of luggage, and thanks to a novel DNA sequencer, the team were able to do just that.

“Genome sequencing information is crucial for researchers and epidemiologists during an epidemic. Yet, generating such information is a laborious process typically performed in well-equipped laboratories using large, delicate and expensive hardware. Having a portable DNA sequencing system opens up the possibility to do outbreak genome sequencing in real-time, which can directly impact on the response on the ground, as well as providing a wealth of information about pathogen evolution.”

The team found that they could generate sequencing information in as little as 24 hours after receiving a sample, with the sequencing process taking less than an hour.

By comparing samples from patients, it was possible to determine whether they were likely to be part of a chain of transmission or if there were unknown networks yet to be discovered. This works because the virus mutated at a constant rate – about 20 differences per year. By comparing the number of differences between samples, it is possible to predict whether they form part of a recent transmission chain or network.

That is useful in understanding the evolution of the virus and aiding control efforts – but only if it can be rapidly provided given to epidemiologists battling to halt transmission of the virus.

“That is where the ‘lab in a suitcase’ comes in. There was not a lot in Josh’s pack - three laptops, some chemical reagents, a centrifuge and a thermocycler we ‘borrowed’ from a lab mate. But the crucial component was a lightweight DNA sequencer called a MinION, made by Oxford Nanopore Technologies. This allowed us to create a fully functioning laboratory that could collate and provide genome sequence information in real time. Crucially, the team working to combat Ebola was on the same page – and by sharing our data and making it available as it was generated we could help provide the information that would shape the development of vaccines.”

Tackling a new challenge
The team barely had time to take stock after the success of the genomic surveillance of the Ebola outbreak before shifting their focus towards Brazil, and the spread of Zika.

“Zika was spreading across the Americas and the Pacific and geneticists were playing catch-up. There were very few publicly available DNA sequences and hardly any from the regions where cases of microcephaly are most prevalent.”

So, using the same model for mobile laboratories that the team had deployed in Guinea, the team took to the roads of north-east Brazil to detect and characterise the early emergence of Zika in large urban centres. Over a 30-day sampling period the team acquired samples from patients in coastal Brazil - from Belém itself in the north to Salvador in the east.

The study showed that Zika’s establishment within Brazil - and its spread from there to other regions - occurred before Zika transmission in the Americas was first discovered.

“We found that northeast Brazil, which was the region with the most recorded cases of Zika and microcephaly, was the nexus of the epidemic in Brazil and played a key role in its spread within Brazil to major urban centres, such as Rio de Janeiro and São Paulo, before spreading across the Americas. Now we have a much better understanding of the epidemiology of the virus.”

“It just goes to highlight the importance of creating trusted cross-institutional partnerships and sharing data openly during disease focused research field work. By not being precious about your data and embracing a more open way of working we can expediate the understanding of the outbreak, and in doing so help public health officials to get it under control and, ultimately, save lives.”

This new method of in-situ genomic surveillance, paired with open data, the team developed a protocol which can be beneficial to other researchers working in remote areas around the world during times of viral outbreaks.

Before the headlines
It has been quite a journey for the Loman group. Though the work on Ebola and Zika made global headlines, their history in genomic surveillance can be traced back further.

In 2011, the team analysed genome data from a German outbreak of Escherichia coli, one of the first to have genome data made available while it was taking place. They were able to show that the strain causing disease was of a type previously unseen in such outbreaks, and tracked the likely source to a strain circulating in humans, rather than animals.

Then in 2014 the team, using the MinION for the first time, were able to successfully study a Salmonella outbreak at a hospital in the West Midlands.

These studies show that foodborne outbreaks can be detected back to source much more quickly and, in the future, food quality may be monitored by producers at source using genomics – all thanks to portable genome surveillance.

“The nanopore technology has changed the field, without a doubt. Rather than waiting for outbreak samples to arrive at sequencing facilities, it allows us why not take the facility to the outbreak?”

A nanopore is exactly what you would think: a small hole.

Most commonly it consists of a small peg-shaped protein with a hollow tube at its core, just a few billionths of a metre wide. In the Oxford Nanopore device used by the Loman lab, the protein sits in a synthetic membrane, submerged in liquid.

When a voltage is applied, creating an electric current across the membrane, ions start to flow through the hollow tube. However, when something blocks the hole, such as a strand of DNA, the ions are impeded and the current drops.

Somewhat handily, the four bases of DNA - A, C, G, and T— change the current in different ways. Ergo if you measure the current, you can decipher the sequence of a DNA strand as it threads through the pore.

What the future holds
The key to the future of this research might well have been signalled by a paper published earlier this year. Using the same MinION technology, the team were able to sequence the most complete human genome ever assembled with a single technology.

At 1,204,840 bases in length, it was 8,000 times longer than a typical sequencing read and more than a thousand times longer than the original reads used to generate the human genome reference sequence in 2001.

As well as sequencing previously uncharacterised regions of the genome, the new analysis provided greater insight into regions of the genome that are responsible for functions such as immunity and tumour growth. This in turn could have a profound impact on clinical practice, for example, detecting large genome rearrangements important in the development of cancer and in determining a person’s inherited repertoire or antibody genes.

Being able to sequence using a portable device that only costs £1,000 may put also personalised genome sequencing into the mainstream.

“Until even just a year ago, it would have been impractically difficult to sequence a whole human genome, but thanks these recent advances and innovations we are making that evermore possible. If you imagine the process of assembling a genome together is like piecing together a jigsaw puzzle, the ability to produce extremely long sequencing reads is like finding very large pieces of the puzzle which makes the process far less complex.”

The inevitable challenge has arrived though. With technology now allowing for far quicker sequencing, the infrastructure is needed to be able to analyse the data at the same rate.

That is why Birmingham is part of CLIMB – the Cloud Infrastructure for Microbial Genomics - a multi-million pound project that is investing in bioinformatics and building ‘big data’ capacity for the UK genomics community.

The heart of the project is four sites; Birmingham, Warwick, Cardiff and Swansea, with a connected virtual computing infrastructure, optimised for specific applications such as microbial genome alignment, de novo assembly and metagenomics.

“The speed of change is really something. As our technology and infrastructure continue to make great leaps, the possibilities for researchers grow exponentially. When you think of where we were in 2001, with a multi-billion, decades-long project to sequence the human genome, and where we are now with sequencing labs on the International Space Station, we know how far we have come. And yet there is so much more on the horizon.”

The work mentioned in this article was only possible with numerous collaborators including:

Ebola
The European Mobile Laboratories, Public Health England and Ontario Institute for Cancer Research, other diagnostic laboratories and WHO epidemiologists based in Guinea.

Zika
Instituto Evandro Chagas, the Institute of Tropical Medicine, University of São Paulo and the Fundação Oswaldo Cruz (FIOCRUZ), in Salvador, Bahia, Medical Research Council (MRC), Public Health England, the Universities of Oxford, Nottingham and Edinburgh, as well as the University of Sydney, Australia and the Ontario Institute for Cancer Research, in Toronto, Canada. The project was funded by the Medical Research Council’s Zika Rapid Response Initiative, USAID, and supported by the Wellcome Trust and the Newton Fund.

Sequencing human genome
Universities of Nottingham, East Anglia, California, Salt Lake City, British Columbia and Toronto, as well as NIH’s National Human Genome Research Institute.

[bamboo2] 09/11/2021 11:37

FT

Pandemic puts Oxford Nanopore ‘on the map’
University spinout’s portable DNA sequencer has proved invaluable in tracking the global spread of coronavirus



If article not available through link, search on google cache for text only version.

[bamboo2] 09/11/2021 09:47

November 3, PEPPER calling now updated to allow use with the new r10 q20 flowcells.



This is the tech that will allow Q20+ on a regular basis. Our accuracy will equal or exceed both Illumina and PacBio on a day to day basis.

If I am reading this right, once evaluated, this will see Genomics England focus on ONT kit for the future expansion of long reads.

for info,


"...We have also collaborated with a team at UC Santa Cruz to train DeepVariant using Oxford Nanopore data. The resulting tool, PEPPER-DeepVariant, uses PEPPER to generate candidates more effectively for Nanopore data. In addition to new models, new capabilities have been added, such as the best practices for cohort calling in v0.9 and DeepTrio, a trio and duo caller, in v1.1. For each release, we focus on building highly-accurate models, reducing runtime, and improving the user experience. In this post, we summarize the improvements in accuracy and runtime over the years and highlight a few categories of changes that have led to these improvements..."

[bamboo2] 09/11/2021 08:07

As I said before, we could be getting upgrades to guidance on a regular basis.

This order has come a month before I thought it would. It looks like UAE are keen to get their deliveries ahead of others.

[bamboo2] 09/11/2021 07:59

Advfn's newstab is not searchable for keywords.
In order to create a searchable RNS news database, I normally post the complete rns on threads.

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9 November 2021

Oxford Nanopore Technologies plc

Update to revenue guidance following expansion of customer project

Oxford Nanopore Technologies plc (the "Group"), the company behind a new generation of nanopore-based sensing technology, is updating its revenue guidance following a significant expansion of the Group's activities in a large customer project in UAE.

On 9 November 2021, the Group was awarded a new 36-month contract under which it will provide devices, consumables including flow cells and kits, and other support services worth approximately US$68 million.

The new contract with G42 Laboratory, LLC, who provide sequencing operations in the project, is expected to generate revenues primarily after the year ended 31 December 2021 ("FY21"). Therefore, the Group is maintaining its guidance of core Life Science Research Tools ("LSRT") revenue of GBP105-111 million in FY21, resulting from growth of 60-70% as announced on 14 October 2021.

Given the scale of the new contract, the Group is now introducing guidance for LSRT revenue of GBP135-145 million for FY22. The Group is also upgrading its LSRT revenue guidance for FY23 to GBP170-190 million, compared to its previous expectation of GBP165 -175 million outlined in its IPO Prospectus.

All revenue guidance figures are provided on a constant currency basis.

As noted in the IPO Prospectus, an affiliate of G42 Laboratory, LLC, is a shareholder in the Group.

[tonsil] 09/11/2021 07:47

On 9 November 2021, the Group was awarded a new 36-month contract under which it will provide devices, consumables including flow cells and kits, and other support services worth approximately US$68 million.The new contract with G42 Laboratory, LLC, who provide sequencing operations in the project, is expected to generate revenues primarily after the year ended 31 December 2021 ("FY21"). Therefore, the Group is maintaining its guidance of core Life Science Research Tools ("LSRT") revenue of GBP105-111 million in FY21, resulting from growth of 60-70% as announced on 14 October 2021.

[ayl30] 09/11/2021 07:06

Good rns re contract win!

[tonsil] 08/11/2021 17:05

Astonishing technical leadership and research all down to ONT. this will revolutionise medicine.

[bamboo2] 08/11/2021 16:39

The Cees Dekker story about using ONT tech for the scanning of single protein molecules is gathering interest.
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In a proof-of-concept study, scientists at Delft University of Technology in the Netherlands and the University of Illinois have successfully repurposed DNA nanopore sequencing technology to scan single protein molecules.

As a helicase enzyme pulls a DNA-bound peptide string through a minuscule membrane channel, researchers can now decode changes in ion currents through the nanopore to read off the individual amino acid building blocks of the peptide one at a time. This ability is a landmark in protein identification, paving the way for single-molecule protein fingerprinting, de novo protein sequencing, and analyzing dynamic cellular proteomes.

The findings are published in an article in the journal Science titled, “Multiple re-reads of single proteins at single-amino-acid resolution using nanopores.”

Until now, information on the primary sequence of proteins has been largely obtained from DNA sequences. But neither DNA nor RNA sequences provide information on the abundance of proteins, their splicing, or their modifications post-synthesis. Despite proteins being the specialized functional machinery in our cells, we fall back on skeletal DNA blueprints to understand proteins.

Methods that do analyze proteins such as mass spectrometry, chop them up into pieces and identify proteins from fragmented spectral signatures through comparisons with protein databases. Such methods are expensive, limited to large volumes, and cannot detect proteins found in low abundance in cells.

In the last few decades, scientists have sequenced single molecules of DNA using a cost-effective and portable nanopore-based technology capable of identifying epigenetic stamps in long reads. Cees Dekker, PhD, professor at Delft University of Technology, and his team have now adapted this method to sequence single protein molecules, one amino acid at a time.

“Over the past 30 years, nanopore-based DNA sequencing has been developed from an idea to an actual working device,” Dekker said. “This has even led to commercial hand-held nanopore sequencers that serve the billion-dollar genomics market. In our paper, we are expanding this nanopore concept to the reading of single proteins. This may have great impact on basic protein research and medical diagnostics.”

Henry Brinkerhoff, PhD, who pioneered this work as a postdoctoral fellow in Dekker’s lab and is first author on the paper said, “Imagine the string of amino acids in one peptide molecule as a necklace with different-sized beads. Then, imagine you turn on the tap as you slowly move that necklace down the drain, which in this case is the nanopore. If a big bead is blocking the drain, the water flowing through will only be a trickle. If you have smaller beads in the necklace right at the drain, more water can flow through. With our technique we can measure the amount of water flow (the ion current actually) very precisely.”

“Peptide sequencing with nanopore technology faces challenges, primarily around the use of the controlled translocation of the molecule of interest through the nanopore for signal readouts from the ion current. For protein sequencing, this issue is further complicated by the overall charge distribution and bulkiness of the molecules,” said Nicholas Schork, PhD, deputy director and Distinguished Professor of Quantitative Medicine at the Translational Genomics Research Institute (TGen) in Phoenix, AZ, who has been working on Nanopore technology for genomics and who is not involved in the current study.

“The study by Brinkerhoff et al. resolved the issue of irregular translocation speed by attaching a short piece of DNA to a target peptide and included the use of a DNA helicase to pull the DNA component of a target molecule through a biological nanopore (MspA) at a controlled speed. As the DNA-peptide molecule is threaded through the pore, the change in ion current is read for the DNA section followed by the peptide section,” said Schork.

This new method of protein sequencing is highly specific and sensitive. The authors showed its ability to detect changes in single amino acid substitutions from changes in ion current readouts.

Dekker added, “A cool feature of our technique is that we were able to read a single peptide string again and again. We then average all the reads from that one single molecule, and thus identify the molecule with basically 100% accuracy.”

In the study, the authors demonstrated their ability to rewind peptide reads to obtaining many independent scans of the same molecule, yielding an error rate that is less than one in a million in identifying single amino acid variations.

Aleksei Aksimentiev, PhD, professor of physics at the University of Illinois and his team performed molecular dynamics simulations that showed how the ion current signals relate to the amino acids in the nanopore. These simulations showed that the changes in ion current signals detected as the peptide string makes its way down the nanopore drain results from size exclusion and the binding of the peptide or its side chains to the inner walls of the nanopore.

“My lab used high-end computer simulations to determine how exactly the sequence of a polypeptide chain influences the blockade current through the MspA nanopore, explaining the counterintuitive dependence of the blockade current on the physical size of the amino acids,” said Aksimentiev.

Chemical groups such as sugar or phosphate groups that attach to proteins after they are synthesized, change their native configurations and add another layer to the complexity of determining the true state of cellular proteomes. Dekker said, “These changes are crucial to protein function, and a marker for diseases such as cancer. We think our new approach will allow us to detect such changes, and thus shine some light on the proteins that we carry with us.”

De novo protein sequencing directly determines the amino acid sequence of a protein without referring to known sequences or protein databases. In its present form, the technology is not capable of de novo protein sequencing.

“Because a mapping of ion current to amino acids is lacking in the approach due to the complexity of this mapping, true de novo protein sequencing remains a challenge. Nevertheless, the proposed method is applicable to identifying peptide sequence variations, as shown when authors compared the results of their amino acid sequencing to known reference proteins harboring amino acid substitutions,” said Schork.

“A real strength of the technique is that it can be implemented using existing nanopore sequencing hardware (e.g. the commercial Oxford Nanopore MinION system) by simply changing sample preparation and data analysis protocols. This will allow studies exploring the strategy to be pursued easily and accommodate improvements in the necessary bioinformatics workflows for interpreting the assay,” added Schork.

Brinkerhoff said, “Our approach might lay a basis for a single-protein sequencer in the future, but de novo sequencing remains a big challenge. For that, we still need to characterize the signals from a huge number of peptides to create a ‘map’ connecting ion current signals to protein sequence. Even so, the ability to discriminate single amino acid substitutions in single molecules is a major advance, and there are many immediate applications for the technology as it is now.”

The technology has several limitations that need further attention, the researchers pointed out. For instance, positively charged peptides may not move efficiently through the nanopore. This, the authors noted, can be addressed by engineering the pore so that peptides move through it smoothly regardless of their charge specificity. Peptides around 25 amino acids long can currently be scanned through this method limiting its application to short peptides. Although this is an improvement over the less than ten amino long peptides that can be identified using mass spectrometry, the read length could be improved through fragmentation and shotgun strategies used in traditional protein sequencing.

“Our findings comprise a promising first step towards a low-cost method capable of single-cell proteomics at the ultimate limit of sensitivity to concentration, with a wide range of applications in both fundamental biology and the clinic,” the authors concluded.

The refinement and adoption of this new technology promises real-time, scalable, affordable, and easy-to-use molecular sequencers for proteins that can change how life scientists and healthcare researchers go about their daily work.

[albert888] 05/11/2021 10:10

Why is there such a big bid/ask spread for Oxford Nanopore?

[bamboo2] 05/11/2021 08:26

This looks like a completely new market for ONT.

The original press release from Delft Uni is here...



Scanning a single protein, one amino acid at a time

NEWS - 04 NOVEMBER 2021 - COMMUNICATION TNW

Using nanopore DNA sequencing technology, researchers from TU Delft and the University of Illinois have managed to scan a single protein: by slowly moving a linearized protein through a tiny nanopore, one amino acid at the time, the researchers were able to read off electric currents that relate to the information content of the protein. The researchers published their proof-of-concept in Science today. The new single-molecule peptide reader marks a breakthrough in protein identification, and opens the way towards single-molecule protein sequencing and cataloguing the proteins inside a single cell.

Proteins are the workhorses of our cells, yet we simply don’t know what proteins we all carry with us. A protein is a long peptide string made of 20 different types of amino acids, comparable to a necklace with different kinds of beads. From the DNA blueprint, we are able to predict of which amino acids a protein consists. However, the final protein can greatly differ from the blueprint, for example due to post-translational modifications. Current methods to measure proteins are expensive, limited to large volumes, and they cannot detect many rare proteins. With nanopore-based technology, one is already able to scan and sequence single DNA molecules. The team led by Cees Dekker (TU Delft) now adapted this technique to instead scan a single protein, one amino acid at a time.

“Over the past 30 years, nanopore-based DNA sequencing has been developed from an idea to an actual working device,” Cees Dekker explains. “This has even led to commercial hand-held nanopore sequencers that serve the billion-dollar genomics market. In our paper, we are expanding this nanopore concept to the reading of single proteins. This may have great impact on basic protein research and medical diagnostics.”

Like beads down the drain

The new technique reveals characteristics of even single amino acids within a peptide, but how? Lead author of the paper Henry Brinkerhoff, who pioneered this work as a postdoc in Dekker’s lab, explains: “Imagine the string of amino acids in one peptide molecule as a necklace with different-sized beads. Then, imagine you turn on the tap as you slowly move that necklace down the drain, which in this case is the nanopore. If a big bead is blocking the drain, the water flowing through will only be a trickle; if you have smaller beads in the necklace right at the drain, more water can flow through. With our technique we can measure the amount of water flow (the ion current actually) very precisely.” Cees Dekker enthusiastically adds: “A cool feature of our technique is that we were able to read a single peptide string again and again: we then average all the reads from that one single molecule, and thus identify the molecule with basically 100% accuracy.”

This results in a unique read-off which is characteristic for a specific protein. When the researchers changed even one single amino acid within the peptide (‘a single bead within the necklace’), they obtained very different signals, indicating the extreme sensitivity of the technique. The group led by Alek Aksimentiev at the University of Illinois performed molecular dynamics simulations that showed how the ion current signals relate to the amino acids in the nanopore.

Scanning the barcode for identification

The new technique is very powerful for identifying single proteins and mapping minute changes between them – much like how a cashier in the supermarket identifies each product by scanning its barcode. It also may provide a new route towards full de novo protein sequencing in the future. Henry Brinkerhoff clarifies: “Our approach might lay a basis for a single-protein sequencer in the future, but de novo sequencing remains a big challenge. For that, we still need to characterize the signals from a huge number of peptides in order to create a 'map' connecting ion current signals to protein sequence. Even so, the ability to discriminate of single-amino-acid substitutions in single molecules is a major advance, and there are many immediate applications for the technology as it is now."

Glimpsing the ‘dark matter’ of biology

Using the current nanopore peptide reader, researchers can start analyzing what proteins float around in our cells. After synthesis in cells, proteins still undergo changes that affect their function, called post-translational modifications. The resulting millions of protein variants are difficult to measure, and could be considered the ‘dark matter of biology’. Cees Dekker: “To continue the metaphor: after a necklace with its beads is made, it will still be changed: some red beads get a phosphoryl attached to it, some blue beads a sugar group, etc. These changes are crucial to protein function, and also a marker for diseases such as cancer. We think that our new approach will allow us to detect such changes, and thus shine some light on the proteins that we carry with us.”

[bamboo2] 05/11/2021 08:03

By coincidence, this article came up on Science daily yesterday, and has since picked up a following on twitter.

Mentioned by Andy Beggs in the recent interview.

Scanning a single protein, one amino acid at a time

Using nanopore DNA sequencing technology, researchers have managed to scan a single protein: by slowly moving a linearized protein through a tiny nanopore, one amino acid at the time, the researchers were able to read off electric currents that relate to the information content of the protein. The new single-molecule peptide reader marks a breakthrough in protein identification, and opens the way towards single-molecule protein sequencing and cataloguing the proteins inside a single cell.

[tonsil] 04/11/2021 16:27

ONT is the Tesla of genomics. Illumina has an mcap of 60billion dollars. They're the VW of the genomics world and are now well behind in technology.

[bamboo2] 04/11/2021 16:15

tonsil, they give their viewpoint from the coalface, with the benefit of years of experience with Pacb, Ilumina, Grail and other older, mainly SBS based systems. They certainly seemed very happy with the nanopore gear.

Nanopore tech does look particularly attractive, in comparison to SBS based systems

Did you pick up on the significance of the Google PEPPER-Margin-DeepVariant calling?
Q35+ is possibly putting ONT ahead of Ilumina.

What is interesting is that this paper was completed before the new R10.4/Q20 flowcells were being shipped. We could therefore extrapolate that expectations of 100% error free reads will become the norm.



ps added more this afternoon at 533.33

[tonsil] 04/11/2021 12:40

Brilliant video to understand the huge advantages of nanopore Thanks for posting. Immediately doubled my holding.

[bamboo2] 04/11/2021 10:16

Posted on November 2, 2021 at 5:01 pm

Novel nanopore sequencing technology used to sequence long reads of over 100 cancer tumours from 100,000 Genomes Project
Findings show benefits of long-read sequencing where structural changes in genome can be spotted more easily
Study is proof-of-concept for Genomics England to build analytical pipeline, with appropriate procurement, for long-read sequencing to be used alongside existing short-read sequencing technology to support clinical decisions

[bamboo2] 04/11/2021 09:17

AFAIK, Yesterdays holding RNS from Red Mile is a post flotation confirmation of their holding of 40817120, having been slightly reduced down to under 5% by dilution or other share issue event.

[bamboo2] 03/11/2021 23:35

Notes. [probs with editing/adding to above post]

These two guys, at the 'wet' lab end of things, are incredible, and will definitely help in your understanding of why you need a good helping of ONT shares in your p/f

8:42
Andy Beggs, [Birmingham] prof cancer genetics and surgeon
Greg Elgar, Dir Sequencing Research, Genomics England

16:50
Methylation, Nanopore beats everything else currently on offer, all the 'old' [SBS] etc

18:30
with nanopore your reading the actual DNA, with SBS, you get to read a secondary copy that is lacking methylation and other modifications.

19:23
Software Google PEPPER Deep variant calling, visual/picture method instead of mathematical approach. Very accurate.

22:30
"GRAIL based methylation is expensive, with Nanopore, it's free."

22:40
Methylation is modifying our DNA throughout our lives

23:30
Nanopore tech is speeding things up, as new base-callers are written old data can be re-processed.

[bamboo2] 03/11/2021 22:30

Genomics England have ambitious plans to expand the use of Long reads in the HNS

To treat cancers, we have to better understand them - and their DNA. Genomics England is pioneering a new technique to sequence the entire genomes of patients with cancer. This is long-read sequencing. Long-read uses an innovative new technique to read very long strands of individual DNA, which can reveal new information about the so called 'dark-matter' of the genome.



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A more detailed view... From approx 8min to 25min, essential for ONT investors

Session recorded at the Genomics England Innovation Showcase 21. [13/10/2021]



Since the launch of the 100,000 Genomes project, researchers and clinicians have partnered with Genomics England to collect and analyse genomic and longitudinal clinical data to gain insight into the nature of genomic changes that drive cancer evolution. This research is ultimately helping clinicians to deliver more personalised treatment programmes and researchers to be able understand disease drivers.
In the next evolution of our cancer programme, we are introducing two disruptive technologies into the clinic and into research:

Long Reads & Methylation: We will be evaluating the clinical and operational impacts of using Long-Read & Methylation sequencing for cancer patients. This new technology can reveal large scale rearrangements in tumour DNA, as well as epigenetic changes that can alter gene expression. The hope is that this new information will highlight new treatment and clinical trial opportunities for patients.

Diagnostic imaging data: We will be enhancing our database in cancer by curating radiology and pathology digital images alongside the genomes of our ~15,000 solid tumour patients, making this the largest multimodal cancer dataset in the world. We will be introducing AI/ML tools that will allow researchers to explore the integrative impact of spatial heterogeneity and regional variations that are associated with the tumour microenvironment, alongside the molecular features of the tumour, in predictive models of response to treatment or prognosis. We anticipate that this resource will unlock new insights into mechanism of action in cancer and could lead to novel prognostic and diagnostic tools.

This session explores our strategy to enhance our tools to characterise cancer ;and about our long-read sequencing and multimodal programmes.

[bamboo2] 01/11/2021 15:04

Copy of post from IPO thread. A few possible catalysts for ONT over the next week or so.

Both ILMN and PACB report 3q figs. PACB is first out of the traps tomorrow, ILMN on Thursday. Both may mention ONT, and their outlooks will be interesting. It's too early to see ONT have any real effect in their respective sp's, but it is notable that they are both busy spending cash on acquisitions to broaden their income streams.

What could affect ONT's competition will be confirmation of regular and reliable Q20+ in the real world, probably through twitter, or at the next community conference at the end of November. The Q30+ tech I would guess will not be made available until 2022.

Also at the end of this month there is an event where it is possible that UAE will make their announcement as to their plans for genomic mapping of the total population.