Another twitter thread on (#NGS) technologies, this time focussing on Oxford @nanopore. The company sells their larger instrument, the PromethION, which has some advantages/limitations over other competing technologies:
The advantages of the PromethION are mainly (1) the read length of Oxford Nanopore's technology, which depending on the sample prep method, can go over several megabases, and (2) it's a high-throughput instrument that can run up to 48 individual flowcells, at the lowest cost.
Another major advantage of the technology is that it's not limited to a 4-letter alphabet of unmodified A,C,G,T, but can also natively basecall commonly epigenetic modifications, such as 5mC (methylation) and others, making the use for epigenomic profiling very straightforward.
If we had to name any disadvantages currently, they would be that the Q-scores are still overall lower than other technologies, namely the short-reads from Illumina or MGI Tech, although recent software/chemistry updates put the median/modal Q-score at Q20+ for single molecules.
Another disadvantage is that for input DNA samples where the fragments are very short, such as those from cell-free DNA from Liquid Biopsy (blood samples, urine, etc.) the overall throughput would be limited unless the material is prepared with some concatenating method.
If we had to estimate the market size longer term for the PromethION, I would base it on two assumptions: (1) that the Q20+ update together with the Duplex technology can achieve a median/modal Q30+ on a consistent basis, including 5th and 6th modified bases in the alphabet.
(2) That cfDNA Liquid Biopsy segment can be catered for with a concatenation PCR-free method that stitches 166bp fragments together making the ONT technology competitive with the equivalent 4-base short read methods.
If these two assumptions are met, the theoretical market size for the PromethION could be as large as the current market size for the Illumina NovaSeq/NextSeq + MGI Tech T7 short read install-base, which is in the mid- to high-thousands currently with an pull through of $1M/pi.
Yet before we can draw scenarios based on these two assumptions, the current market size is best suited for (1) inherent long-read applications, which encompasses everything except the biggest segment, cfDNA liquid biopsy (cancer and NIPT), and (2) fast TAT surveillance (COVID).
The latter is due to the nature of the ONT technology, where assaying a single molecule through one of the pores takes only seconds, thus getting to an answer for fast turn-around applications can be much faster than SBS or related methods which take hours/days.
In both (1) and (2), ONT can already take share from established companies like Illumina, but also competing long-read technologies like PacBio. The fact that there is a very low-CAPEX barrier to entry into the ONT technology means that they can quickly gain market share on ...
... a tech-only basis, and then the sales and marketing side of the competitive playfield will also play a part. PacBio has in the last 1-2 years grown in size as an organization and capitalization, which means that ONT will have to catch-up with both Illumina and PacBio.
Back to PromethION: placing ourselves again in the scenario where they can (1) reach a median/modal Q30+ with Duplex basecalling and (2) enter the cfDNA liquid biopsy segment with a PCR-free concatenation sample prep, this would speed-up clinical adoption of the instrument.
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15 Sep
In #biotech #stocks today, I highlight $BLI Berkeley Lights which is currently down -11%. The trend is still looking downwards since Dec 2020 when it had a remarkable burst of what I would call "frothiness" and since then it's been on a gentle downwards trajectory.
Sometimes these big short hikes are not entirely rational, and as of late, with the emergence of the meme stock phenomenon, normal decent-looking #biotech companies can be hijacked by pump-and-dumpers that don't even care at all about what they invest in.
This is nowadays magnified by the Robin Hood's of the world of investing, which act as an amplifier of the crowd behaviour that is decoupled from any logical thinking.
Read 6 tweets
14 Sep
Oxford @nanopore vs #Illumina #NovaSeq: how far away are they from each other?
I followed with attention the recent PromethION updates, both in terms of new flowcells, with denser pore surfaces, and software and reagents, with the Q20+ basecalling.
It is reasonable to assume that the rollout of the Q20+ updates will be commonplace in the next few months, which means that there is only another decimal in base calling accuracy to put the ONT technology on par with Illumina short-reads. Oxford Nanopore has already announced...
... their work and preliminary results for their updated dual strand base calling, and the modal shows a peak near Q30, which means there wouldn't be much to debate anymore when it comes to per-base accuracy between the two technologies.
Read 11 tweets
2 Sep
In #biotech #stocks news, one of the #LiquidBiopsy #CancerDx stocks in my list is $BNR Burning Rock, a company with presence mainly in Asia that started trading in the NASDAQ a while ago. It is now at lowest levels having recently gone below the $20 mark Image
At around $2B valuation, they are still in the top 10 of companies in the #LiquidBiopsy #CancerDx field: Image
Notice that #GrailBio is still marked at $2B valuation in my table: this is not the $8B figure that #Illumina is intending to buy it at, but I'll wait until the acquisition is completed (and not legally challenged by the US/EU authorities) before updating the value in the table.
Read 10 tweets
31 Aug
Industry Overview on Biotechnology and Genomics Space (thread):
The era of genomics has now decisively entered the applied sectors of the market, after many years, decades, where the RUO segment was the largest piece of the pie. The lines between genomics and Medtech industries are now blurred and there is lots of crosstalk between both.
Who are the main players in the space: Illumina should be first of the list by market share, with Thermo Fisher Scientific second by overall company size. BGI Genomics dominates in China (NIPT, Cancer Dx). Smaller but distinct in some offerings is Qiagen, who at a point was ...
Read 8 tweets
24 Aug
In the #biotech #stocks #NGS field, there is a company that's recently IPOed and has now presented an update of their plans: $OMIC Singular Genomics @SingularGenomi1…
Their two planned instruments, the G4 and the PX, look physically a lot like competitors to the #Illumina NextSeq and NovaSeq, or the #MGI #DNBSEQ G400 and T7 instruments. But the PX is more of a multi-omics play rather than a higher throughput #NGS machine.
It seems we are about 1 year or 1.5 years away from Early Access / Commercial Launch for the PX, maybe around 6 months earlier for the G4 instrument.
Read 9 tweets
24 Aug
Good to see that #NextGenSequencing #NGS is become more and more available worldwide.
There is an argument that in markets where #Illumina has lesser IP coverage to block #MGI #DNBSEQ instruments, the fight for the #shortreads market will become more akin to the 2024 IP cliff for #Illumina. An example here, but also China, certain Eastern Europe countries, ...
Read 4 tweets

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