The Long and the Short of it – PacBio’s ASHG Announcements

PacBio's Onso SequencerThe sequencing market continued its “Big Announcement Season” at ASHG and this time it’s PacBio’s turn. Not to be outdone by Illumina’s NovaSeq X announcement, they introduced TWO major sequencing platforms - one for long reads and one for short reads.

Long Reads

Their new long read platform announcement came with a good level of detail. Behold the launch of the Sequel III! Oh, wait, no. My mistake. They went with Revio, a name surprisingly similar to the defunct single molecule sequencing company Reveo. First, let’s say what this sequencer ISN’T. It isn’t the desktop long read sequencer they’re working on with Berry Genomics. It also isn’t the super high throughput long read sequencer they are (were?) working with Invitae to create. Instead, it’s a very solid improvement on the Sequel II. Roughly the same level of improvement that the Sequel II was over the Sequel. Hence my strong desire to call it the Sequel III. 

They’ve gone from an 8M feature SMRT cell to a 25M feature smart cell (not quite the 64M chip many have been expecting) - a roughly 3X improvement. They also increased the number of SMRT cells run in parallel to four - a 4X improvement. (No word on if these parallel SMRT cells can be operated independently.) And they’ve dropped the runtime from 30 hours down to ~24 hours. Mix it all together and you get a pretty nice 15X improvement in throughput over the Sequel II. And while they’ve nearly doubled the instrument price to $779k, PacBio has finally hit the mythical $1000 genome with 30X HiFi reads. Will this price drop be enough to move people away from Illumina’s $200 30X short read genome? And will the throughput of 1300 genomes per year be enough compared to the NovaSeq X Plus output of 20k genomes per year? It won’t start shipping in 2023 H1, so we’ll have to wait several months to find out. (Edit: between the first draft of the press release and the final version they moved up the shipment schedule to 2023 Q1, so we'll find out a little sooner.)


Short Reads

A little over a year ago PacBio acquired Omniome, a startup working on a high quality short read “sequencing by binding” platform. The idea was that since they couldn’t merge with Illumina, they felt they needed their own short read platform to go after the pretty substantial segment of the market where short reads make more sense, especially in the clinical space. They’ve been touting reads that are >90% Q40 for a while. But since Omniome never really built a machine, the market has been waiting to hear exactly what this new short read box would look like, just how short these short reads would be, what it would cost to buy, and what it would cost to operate ($/Gb). PacBio didn’t reveal everything, but they’ve answered most of our questions. And they’ve given it a new name - Onso. Well, it certainly has some letters. Four of them. Well, three different ones. Onso. Hmm.

Anyway, here’s the important stuff. It will indeed be a desktop system selling for $259k, so on the low end of the main desktop systems (not counting the venerable MiSeq or smaller MiniSeq). They reiterated the quality spec of >90% Q40 reads. It is slated to generate about 500M reads of up to 2X150b (for 150Gb of output), but no word yet on what those reads cost. The competitors are in the range of $6/Gb (Element Biosciences) to $20/Gb (Illumina’s NextSeq 1000/2000), so it seems likely that they’d try to land somewhere in there. It’s possible they’ll aim for the higher end with the argument that higher accuracy reads are worth more. The other thing to consider is that Revio will have a price of $10/Gb. Short reads have historically been cheaper than long reads, but desktop system reads have been more expensive than high throughput sequencer reads. It will be really interesting to see how PacBio prices this. They won't be accepting orders until early 2023 (with shipments slated for 2023 H1), so we may not learn the answer until then.


Market Impact

Will Revio's cheaper long reads accelerate the relatively slow transition from short reads? Will Onso's higher quality short reads chip away at Illumina's dominance? These are all pretty forward looking statements from PacBio, so it will probably take a year or so until we start seeing any potential trends. Stay tuned!

Revio Press Release

Onso Press Release

Shawn Baker

View posts by Shawn Baker
Founder and principal consultant at SanDiegOmics
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