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.
More at bit.ly/ngsspecs
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