In #NextGenerationSequencing news, we look at the clinical uptake of different NGS technologies after the recent updates announced in the last few months:
NGS has been dominated by Illumina with their SBS short-reads technology, with reads of up to 2x150 base pairs available in most configurations, although 2x300 are also possible at a higher cost per Gb.
If we could roll back time in the last 15-20 years of NGS history, we would ideally have had a long-reads technology, or better yet, a length agnostic technology, be the dominant player, as most applications, both in Life Sciences Research and Clinical, would have benefited
from reads longer than the ones Illumina produces. As such technologies, long-read or length agnostic evolve, we should see a segmentation of the Clinical market where some applications are done exclusively via long-reads, whereas others remain as Illumina SBS applications.
One example of the later could be Liquid Biopsy, e.g. for cancer screening, by sequencing of the cell-free DNA that circulates in our blood stream. It just so happens that the length of the majority of such DNA fragments is about ~166bp, which is well suited for short-reads.
The market for Liquid Biopsy, and particularly for cancer screening, could grow up to be a $10B, or $30B or even $50B market, depending on when we place the landmark and how we define it. But taking together cancer screening and MRD, Non-Invasive Prenatal Testing (NIPT) and
similar segments, there will be still a big appetite for short-reads. The Grail takeover merger is an examle of the strategic importance that Illumina places on Liquid Biopsy diagnostics. Will they be allow to vertically integrate in such a way, and thus punish the Guardant
Health and Exact Sciences of the cancer screening world: probably not.
Then what else is amenable to long-read technologies in the Clinical space? Literally everything else.
An example here is the genomic sequencing of new born babies. At the moment this is restricted to neonates that present a phenotype that may be triggered by a genetic condition, but if we project this into the future, there could be a near future where every single new-born has
their genome sequenced at birth, and this becomes their first element of their electronic health records. We've seen examples recently of how good genome sequencing and assembly can become with long-read technologies, such as PacBio HiFi reads, and even more complete with the use
of Oxford Nanopore Ultralong read sequencing, where each read can reach length of over a megabase, which is a couple of orders of magnitude longer than the standard genomic DNA prep, e.g. the transposase-based prep of genomic DNA that Oxford Nanopore offers.
A combination of those two would deliver a complete assembly, even crossing over the centromeres, of a human genome, at which point, this initial EHR becomes a reference on top of which other layers of multi-omic information can be layered over.
The use of these technologies is becoming more mainstream, and recent advances both by PacBio with their new Revio system, and Oxford Nanopore with their Kit14 and more recently with the preview of their "stereo duplex" and 1000-base-per-second upgrades will mean
that the advantage that Illumina used to have, in sheer throughput and availability of their systems, is narrowing. Illumina's revenues are also not growing as they used to, whereas Oxford Nanopore has had their last two years of excellent growth in revenue, with the last one
sustaining good revenue even after discounting the COVID-19 variant surveillance revenue that peaked two years ago. The fact that Oxford Nanopore is very attractive in terms of CAPEX and can be widely deployed in a range of setups is an advantage for the growth into clinical use.
As a comparison, the newly announced Revio instrument by PacBio will deliver a near 30x HiFi genome for $1000, with the instrument at a price of $779,000 and capable of producing 1,300 genomes per year.
Oxford Nanopore has been selling instrument that already outmatch the Revio in throughput, with the P48 capable of producing ten times the number of genomes per year. The new P2 instrument is also a very attractive proposition, with a starting price of $10,500, it is ideal for
setups where the NGS doesn't need to be a centralised core factory setting, and the instrument can remain available as the samples come in for sequencing, e.g. in a small hospital or health centre.
The new Revio at $1000 per HiFi genome, and the Oxford Nanopore Kit14 Promethion flowcells are already close enough to the Illumina short-read equivalent that many clinical applications can switch to long-reads without a significant impact in their operations.
In fact, the new P2 instrument by Oxford Nanopore opens new doors for Clinical applications in settings where neither a large Illumina or PacBio instrument could be placed so far. This is a new boost for growth in the NGS space where other instrument types are already saturated.
There are aspects of familiarity, especially in sample extraction and library preparation, where these long-read technologies will have to continue educating the customer base. The fact that Illumina SBS is limited to short-reads meant it didn't matter if the input source of DNA
got damaged, i.e. fragmented, during extraction and preparation, which is not the case with long-read technologies. Here, the better we purify the DNA, the better the read-out we will get. Considering that both PacBio and Oxford Nanopore can read 5mC out of native DNA, means we
also get the epigenetic information on top of the genetic read-out of a sample.
These are exciting times for NGS, and if you want to read more about them, follow this account and go to for a summary of the who is who of NGS.

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More from @AlbertVilella

Dec 9
A few notes on the Oxford Nanopore Tech update, not complete by any means, the link to the 1 hour presentation is below.
Sample recovery: take your DNA back after a sequencing run, re-run it on another flowcell Image
New MinION Mk1D: better temperature control, can interface with Apple's iPad Pro via a dock ImageImage
Read 20 tweets
Oct 19
In Next-Generation sequencing news, we have been digesting the Chemistry X and $200/genome announcement by $ILMN Illumina for a few weeks now, and next in line are $PACB PacBio, MGI Tech and $ONT.L Oxford @nanopore to give updates between now and the year end.
The $200/genome announcement by Illumina puts pressure on the other short-read high CAPEX instrument companies, which at the moment would be MGI Tech and Ultima Genomics. Both will have to deliver on their promises of a $100/genome, which they both have made recently.
In terms of the long-read market, the $200/genome is a still a short-read play, and thus should not put pressure on PacBio and Oxford Nanopore in that regard. Illumina had to concede that long reads are important, and their Infinity technology strategy is a demonstration of the
Read 20 tweets
Oct 17
Some back of the envelope calculations on the recent announcements by $ILMN Illumina make me think there may have been two lines of pricing being considered when launching the NovaSeq X Plus instrument line. The "conservative pricing" could have placed the 25B flowcell at $3/Gb. Image
Then placing the 10B flowcell somewhere in between the $3/Gb and the $6/Gb on the NovaSeq 6000 instrument, maybe at $4.5/Gb.
This would probably have matched MGI Tech's unofficial pricing of $6/Gb on the mid-throughput sequencer, where Element Bio @ElemBio is also priced.
And their DNBSEQ T7 equivalent to the NovaSeq 6000 at $4.5/Gb, maybe better? Their DNBSEQ T10x4 could already be at $1/Gb, but it's a larger installation and commitment than the NovaSeq X Plus 25B flowcell (H2 2023), and pricing isn't clear on it yet.
Read 5 tweets
Oct 5
Another day, another tweet about Next-Generation Sequencing, this time comparing four companies that have a play in short-read NGS with markedly different histories so far: $ILMN Illumina, $OMIC Singular Genomics, Element Bio @ElemBio and @UltimaGenomics :
All four companies listed here are in the short-read Next-Generation sequencing realm, with Illumina being the 800-pound gorilla of NGS with 80-90% of the marked share, and having recently announced their NovaSeq X Plus instrument line to consolidate their leadership in the
high-throughput part of the market. Second is Ultima Genomics, which is a private company that recently came out of stealth, and announced their plans to release a high-throughput short-read sequencer in 2023 capable of doing $100 genomes ($1/Gb). No confirmation on the price
Read 12 tweets
Oct 3
Thank you all who followed the $ILMN Illumina updates last week via this twitter account. I suspect things will calm down until the next announcement in NGS ($PACB PacBio / $ONT.L Oxford Nanopore / MGI Tech in the next few weeks). Meanwhile I'll carry on tweeting...
... about related topics such as:
Synthetic Biology and DNA synthesis (
Next-Generation Proteomics (
Single Cell and Spatial Biology (…)
Liquid Biopsy and Cancer Screening (
As well as:
Bioinformatics Compute Acceleration ( / more on the Computers geeky side)
Biotech stocks and tech stock market trend ( financial/strategic as well as the technical/scientific side)
Read 4 tweets
Oct 2
On #biocompute news, $TSLA Tesla AI day gave some technical details on how they do their training and video labelling. It seems $NVDA Nvidia GPUs are the norm, with a 14,000 HPC heavily optimised on the software side. #pytorch #AVX2 #CUDA #SMT #smol #CUDNN Image
None of this is for the purpose of #Bioinformatics applications, rather here it's for Full Self-Driving software, but the technical details show some choices for high-throughput #AI training that one could compare to the #ComputationalBiology #ComputeAcceleration world.
Read 12 tweets

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