Oxford Nanopore Technolo... Share Discussion Threads

[bamboo2] 23/2/2022 23:36

BBC Radio 4 23/2/2022
Inside Health
Rapid genome sequencing in the clinic.

[Euan Ashley & co discussing, in laymans terms, their recent progress]

[bamboo2] 21/2/2022 13:58

Clive Brown [tech dir] tweets...

For our customers, this is the pore-motor combo from the top left, so a new variation of the Q20+ chem we already released. Looking like Q23+ and still improvable.



Q20 to Q23 in two months is pretty good and shows the rate of change in accuracy improvement is increasing. Additionally, third parties are upgrading their basecalling software and processes.

Elsewhere, eDNA [environmental DNA] is getting mentioned quite a bit, and the portability of the MinIon lends itself perfectly to 'in the field' Metagenomics.

[bamboo2] 19/2/2022 07:04

Guinness World Record Awarded for Fastest DNA Sequencing — Just 5 Hours
Record was set by researchers from Stanford University, with collaborators from NVIDIA, Oxford Nanopore Technologies, Google, Baylor College of Medicine and the University of California at Santa Cruz.

February 18, 2022 by ISHA SALIAN



Guinness World Records this week presented a Stanford University-led research team with the first record for fastest DNA sequencing technique — a benchmark set using a workflow sped up by AI and accelerated computing.

Achieved in five hours and two minutes, the DNA sequencing record can allow clinicians to take a blood draw from a critical-care patient and reach a genetic disorder diagnosis the same day. The recognition was awarded by a Guinness World Records adjudicator Wednesday at Stanford University’s Jen-Hsun Huang Engineering Center, named for NVIDIA’s founder and CEO, a Stanford alumnus.

The landmark study behind the world record was led by Dr. Euan Ashley, professor of medicine, of genetics and of biomedical data science at the Stanford School of Medicine. Collaborators include researchers from Stanford, NVIDIA, Oxford Nanopore Technologies, Google, Baylor College of Medicine and the University of California at Santa Cruz.


“I think we are in unanimous agreement that this is nothing short of a miracle,” said Kimberly Powell, vice president of healthcare at NVIDIA, at the event. “This is an achievement that did go down in the history books, and will inspire another five and 10 years of fantastic work in the digital biology revolution, in which genomics is driving at the forefront.”

Diagnosing With a Genome in Record Time
The researchers achieved the record speed by optimizing every stage of the sequencing workflow. They used high-throughput nanopore sequencing on Oxford Nanopore’s PromethION Flow Cells to generate more than 100 gigabases of data per hour, and accelerated base calling and variant calling using NVIDIA GPUs on Google Cloud. A gigabase is one billion nucleotides.

“These innovations don’t come from one individual, or even one team,” said Greg Corrado, distinguished scientist at Google Research, at the event. “It really takes this group of people coming together to solve these problems.”

To accelerate every step — from Oxford Nanopore’s AI base calling to variant calling, where scientists identify the millions of variants in a genome — the researchers relied on the NVIDIA Clara Parabricks computational genomics application framework. They used a GPU-accelerated version of PEPPER-Margin-DeepVariant, a pipeline developed by Google and UC Santa Cruz’s Computational Genomics Laboratory.

“I believe that the innovations that we’ll see in biology and medicine in the coming century are going to depend on this kind of collaboration much more than the siloed R&D centers of the past,” Corrado said.

New Possibilities for Patient Care
Ultra-rapid genome sequencing isn’t about setting world records. Cutting down the turnaround for a genetic diagnosis from a couple weeks to just a few hours can provide doctors with rapid answers needed to treat critical care patients, where every second counts.

And, as the technology becomes more accessible, more hospitals and research centers will be able to use whole genome sequencing as a critical tool for patient care.

“Genomics is still at the beginning — it’s not the standard of care,” said Powell. “I believe we can help make it part of the standard by reducing the cost and the complexity and democratizing it.”

Not content with the five-hour record, the team is already exploring ways to decrease the DNA sequencing time even further.

“There’s one promise we will make. We will smash this record very quickly in collaboration with Euan and his team, and NVIDIA and Google,” said Gordon Sanghera, CEO of Oxford Nanopore Technologies.

Hear more about this research from Dr. Euan Ashley by registering free for NVIDIA GTC, where he’ll present a talk titled “When Every Second Counts: Accelerated Genome Sequencing for Critical Care” on Tues., March 22 at 2 p.m. Pacific.

[bamboo2] 17/2/2022 09:10

News updates from past few days...

First test run of the Mk1C for use in spaceflight from last week. Library prep in only 10 minutes. It’s incredible progress that we can now perform omics sequencing in the palm of our hands!



London Calling Conference confirmed for 18-20/5/2022. This year’s event is hybrid, you will be able to register to attend London Calling 2022 in person or online. Investors welcome.



Most university ordering systems will barely have added the new kits before they have been replaced at the current innovation pace of nanopore.

[bamboo2] 11/2/2022 07:45

What is John Gorzynski planning to do with all those Flowcells? [At least 50!]

This has to be another attempt on the world record, probably using the updated ONT tech.

The great thing is, results are known in just a few hours, so we can anticipate headlines very soon.

[ptolemy] 09/2/2022 10:24

Bamboo, A big thanks. I'll have a read.

[bamboo2] 08/2/2022 19:07

Ptolemy, start with Evaluate article. It's actually quite negative.

Albert Vilella, who is quoted in the article has gone on to buy shares in the co.
There are some inaccuracies, such as the costs. For some reason they have ignored the fact that Ilmn and Pacb are very large machines that require a lab and all the expensive infrastructure that that entails.



I can write a list of the numbers of key posts in the thread if you want.

Technical Dir Clive Brown's update from Dec '21 [on youtube] is good [although he has a cough, so wear a mask!]. Flick through using the time based index below the vid.



The history of the co is here...


Forbes now running an alternate take on the high speed genetic testing story

[ptolemy] 08/2/2022 12:47

I'd like to read something about ONT that provides a big picture view, but nothing too technical. Can anyone suggest a note/release etc. TIA

[bamboo2] 08/2/2022 08:01

This story now going more mainstream...

Rapid DNA Sequencing Tech Breaks the Speed Record for Reading Whole Genomes
By Kevin Doxzen -Feb 06, 2022 Read by 3,836



Record-breaking rapid DNA sequencing promises timely diagnosis for thousands of rare disease cases
February 3, 2022 1.11pm GMT

[haggishunter] 08/2/2022 05:27

thanks babamboo2 really excited about this company.

[bamboo2] 07/2/2022 17:14

edward, thanks. There are so many papers concerning ONT being published at the moment, it is hard to keep up.

The recent improvements to the kit are being really well received. I am following James Ferguson, Taco Jesse, Alex Wittenberg and others, as they are keen early adopters of the tech.

Full duplex and re-reading tech should mean we are on a par with Ilmna and Pacb, with more functionality, and better value.

[edwardt] 07/2/2022 14:47

love these updates bamboo - what a great british success story this stock will be over the next decade!

[bamboo2] 06/2/2022 14:33

Twitter thread from Taco Jesse in the Netherlands suggesting positivity of results from the recent upgrades.

BREAKING

The LongRead Race is Over

Victory for Oxford Nanopore

[bamboo2] 06/2/2022 10:57

Twitter thread from James Ferguson at Garvan, unpacking and commissioning P48 [6 Feb 2022]

Time for a @nanopore PromethION upgrade. Going from old P24 to a new and improved P48, hot off the production line in Oxford.

[bamboo2] 06/2/2022 10:52

Editorial on the recent news from Garvan Institute

h ttps://www.zdnet.com/article/new-file-format-helping-researchers-reduce-dna-analysis-time/

Written by Aimee Chanthadavong, Senior Journalist
on February 2, 2022 | Topic: Big Data

The University of New South Wales and the Garvan Institute of Medical Research have developed a new computer file format to speed up nanopore sequencing analysis and improve specialised treatments for patients with cancer and other diseases.

Published in Nature Biotechnology, the research said the newly developed SLOW5 format can process complex DNA nanopore sequencing "more than 30 times faster" than the previous file format called -- ironically -- FAST5.

Nanopore sequencing is used to identify a range of diseases and help medical professionals analyse DNA samples in detail so they can provide tailored treatments for cancer patients.

The data produced from this process was routinely recorded in FAST5 file formats, which produced large files of around 1.3 terabytes, equivalent to roughly 650 hours of high-definition video. Due to its large size, it would take two weeks for computers to process the FAST5 files, the researchers said.

However, lead author and Garvan Institute genomics computing systems engineer Hasindu Gamaarachchi said processing data for human genome using SLOW5 is reduced to half a day.

He explains that unlike FAST5, the SLOW5 format enables parallel computing whereby several processors can simultaneous execute multiple, smaller analyses broken down from larger, complex, and complete dataset.

"You can think of this like trying to dig a very big hole with 10 people, but there is only one shovel they have to share round. That's how it used to be with FAST5," he said.

"But with SLOW5 everyone gets their own shovel, and they can all dig at the same time and do the job much faster.

"The FAST5 format is slow because the data cannot be accessed in parallel. It is based around the Hierarchical Data Format which was designed in the 1990s to work on machines which at the time only had one processor, rather than the modern ones which include multiple processors.

"The Hierachical Data Format is also generic, whereas the SLOW5 is purpose-built. So in terms of the digging analogy, it's like we are also providing a shovel that is specially designed for the type of soil. And because the new SLOW5 can be accessed in parallel by multiple processors at the same time, the processing time has reduced by a factor of 30."

[bamboo2] 06/2/2022 10:49

JP Morgan Healthcare Conference Presentation

[bamboo2] 06/2/2022 10:26

haggishunter, March 2022
{my chart currently suggesting 22/3/22 is a possible news day}

[haggishunter] 05/2/2022 18:07

does anyone know when will there be a trading update?

[bamboo2] 03/2/2022 21:09

New method and model address blindspot towards uncommon species in mixed samples



Existing methods have created a ‘biodiversity blindspot’ towards the rare; meaning low abundance species may be underrepresented, while genetic variants could be missed altogether. This current oversight could, for example, fail to spot crucial information about resistance to antibiotics or delay the point at which the emergence of a new strain becomes detectable.

By combining advanced sampling techniques with mathematical models, using Oxford Nanopore Technology’s software, Earlham Institute scientists were able to amplify and enrich metagenomic samples to reveal crucial details that may have been unidentified before.

Metagenomics approaches are used to analyse genomic function and diversity of complex microbial communities from environmental, agricultural and clinical settings.

The whole-genome shotgun approach in metagenomics enables the reliable identification of organisms down to species and strain level. This allows microbiologists to evaluate bacterial diversity and detect the abundance of microbes in various environments.

A popular tool for understanding mixed species, metagenomics is particularly used for analysing individual species (that cannot be isolated from their environment), or gene clusters such as antibiotic resistance genes - to shed light on genomic function or generate reference sequences for unculturable organisms.

With the increasing use of long read technologies, either on their own, or combined with short-read technologies, metagenome assembled genome (MAG) contiguity and accuracy metrics have improved. Such approaches have been widely applied including assembling pathogen genomes from clinical samples, bacterial genomes and gene clusters from the human gut to the rumen microbiome of cattle.

Yet, despite these successes, difficulties still remain about the reliability of MAG approaches when faced with complex populations. As a solution, scientists at the Earlham Institute applied a new approach called adaptive sampling, which is a method for software-controlled enrichment unique to nanopore sequencing platforms.



By creating a model and evaluating the use of adaptive sampling approaches, the team tested its potential for enrichment of rarer species within metagenomic samples - producing a synthetic mock community and constructed sequencing libraries with a range of DNA molecule lengths. The team also tested model communities of gut microbes and evaluated performance on complex microbial community samples taken from a garden compost heap.

Study lead and Group Leader at the Earlham Institute Dr Richard Leggett, said: “Metagenomic samples are composed of a range of different species at varying levels of abundance. This can mean that sequencing these samples produces data resulting in deep coverage of some species; with low or partial coverage of others.

“For rarer species, this is likely to result in much poorer assemblies and a reduction in the ability to distinguish between strains or related species. Effective enrichment strategies to maximise the sequence outputs of the rare species would address this weakness, and biodiversity blindspot.”

Adaptive sampling offers a potential solution to enrich species of interest in metagenomic samples. Using a relatively simple library construction method, samples can be prepared for sequencing within an hour without the need for amplification. However, a challenge for microbiome research is the difficulty of extracting long intact DNA molecules from complex metagenomic samples.

“Reducing host DNA is an important consideration in many diagnostic applications, especially in clinical settings. We wanted to investigate the effect of DNA molecule length on the efficiency and efficacy of adaptive sampling to determine its usefulness for both MAG and diagnostic applications.”

First author and Postdoctoral Scientist at the Earlham Institute Dr Samuel Martin, said: “In our study, we present a mathematical model that can predict the enrichment levels possible in a metagenomic community given a known relative abundance and read length distribution. Through Oxford Nanopore Technology’s adaptive sampling approach, we demonstrated enrichment in terms of both yield and composition, in a synthetic mock metagenomic community and in a complex real sample.

“We found that enrichment was higher for less abundant species, and for libraries with a higher average molecule length, showing that extraction methods that can preserve molecule length are key to obtaining the highest enrichment.

“By performing targeted enrichment on a low abundance species, we were able to significantly reduce the time taken to achieve a high accuracy, single-assembly, compared to non-targeted sequencing. We expect that adaptive sampling will prove to be a useful tool for many nanopore-based metagenomic studies.”

‘Nanopore adaptive sampling: a tool for enrichment of low abundance species in metagenomic samples’ is published in Genome Biology.

[bamboo2] 03/2/2022 16:53

There have been recent upgrades to chemistry and software, that are now starting to be shipped in greater numbers.

As a result, there have been some updates to existing third party base-calling software, such as PEPPER-Margin-DeepVariant, and some additional software releases, that make use of new features.

Readbouncer is new software that makes use of the Adaptive sampling [if I have understood it correctly] improving accuracy and speed, for use particularly in metagenomics and pathogen identification. Both these application areas are likely key targets for the deployment of ONT kit in healthcare and environmental settings.

{edit - having read up a bit more on the new features introduced by ONT, Readbouncer could be making use of the 'Read Until' function. I think this is software controlled.}

The main benefit is almost immediate pathogen ID [within two hours], completely sidestepping the need for the use of cultures [This can take days]. Further, it is likely that this will be able to be used in blood analysis, to ID antibiotic resistance genes, allowing frontline staff to quickly select the correct treatment for infection first time.

The liquid biopsy platform, currently in development, would likely be a natural partner for this tech.

[bamboo2] 31/1/2022 19:52

edward, yes this is symbiotic set-up, where both parties benefit.

ONT has access to the massive petabyte scale cloud storage and processing that is required for long reads.
Oracle further broadens its investment in healthcare.



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We have heard much about the new world record genetic diagnosis in the ER depts on West Coast of US. In this work they struggled to process the real time data output from the PromethIon. Cloud based tech sidesteps this issue. [In this example Google cloud was used]

[edwardt] 31/1/2022 17:01

bamboo - can you describe what the tie up with Oracle? i assume they offer cloud solutions for the data?

[ayl30] 28/1/2022 10:00

Thanks for the input

[edwardt] 28/1/2022 09:56

blimey/ i am going to close my eyes and add.