Tuesday, January 19, 2021

J.P. Morgan: PacBio

PacBio CEO Christian Henry’s presentation at J.P. Morgan wasn't rich in technical specifics. But he gave a very bullish portrait of a company aiming for the stars.  A conflict reminder: he’s a member of the Board of the Strain Factory that employs me, though I haven’t yet had the pleasure of meeting him.

The biggest news is a broad partnership with Invitae four clinical human genome sequencing. The only specific here is that this is not the whole enchilada; platform development will take place both within the Invitae collaboration and outside it. What might that development be?

Between Henry’s comments in the Q&A and a few info crumbs on slides there will be pushed to further tune all the canister. Her mentioned efforts on dyes and further improving SMRTcell loading efficiency. There was chatter on Twitter about an overdue update to improve HiFi yields.

Henry talked of the importance of increasing ZMW packing, but gave no specifics other than to suggest this is more "development" than "innovation" -- this was in response to a question asking if technical breakthroughs are required.   But we are left wondering on a timetable as well as what the next density might be; four-fold to 32M  wouldn’t be surprising on naïve geometry grounds. 

I suspect a huge area of joint effort with Invitae will be to automate HiFi library production. The current protocol is long, manual and labor intensive - not at all appealing for lease scale clinical use. How much of that will be retained as proprietary to Invitae will remain to be seen.  Henry claims that the Invitae effort will be separate but coordinated with existing development efforts; prior plans have not been shelved or diverted to support Invitae. A major software effort to support clinical operations is a given. PacBio has separate workflows for SNP and SV calling and those must be integrated and a clinician-friendly report generated. 

Henry believes that the new Sequel IIe will be the dominant product shipped going forward.  It will be interesting to see which of the older workflows PacBio updates and moves into the on-board compute.  For example, if you want to call methylation you must export BAM files with kinetics data, which are predicted to be five-fold fatter.  If the methylation calling happened on board, then that extra processing and extra data would be eliminated.  

Similarly, workflows such as microbial assembly are still based around Continuous Long Reads (CLR).  Henry didn't mention CLR once (I think).  While I doubt they would ever dump it altogether like they did Strobe Reads, it would seem likely that it won't get much attention.  Oxford Nanopore can beat them on very long reads and their single molecule accuracy is much higher; far better to focus on the CCS/HiFi reads where PacBio can deliver much higher accuracy.  It will be interesting to see if PacBio pushes the HiFi fragment read length longer.  On the one hand it will be more challenging to work with longer fragments and to routinely get enough circuits around them to deliver HiFi quality data.  Twenty five kilobases is a nice size for many applications, but there will always be incremental value for going to thirty or forty or beyond.

In response to a question about $1000 genomes, Henry described it as "just a number" around "where it makes sense" in high throughput applications.  He says the Invitae collaboration will be able to drive prices below $1000.  But he also pushed the idea that a PacBio genome is a truly clinical grade genome and has higher value than genomes produced on other platforms.  He argued that this higher value, in terms of higher diagnostic yield for rare diseases, will be more attractive to payers and that there will be a net benefit to the healthcare industry by ending diagnostic odysseys sooner.   He vowed to continue generating "diagnostic proof statements" to provide evidence to support the higher value claim.

Should be interesting to watch, particularly if you have a front row seat in front of a Sequel IIe,

1 comment:

Anonymous said...

not a lot of detail. given their exuberant price is now 100X their declining revenues, this is all loaded with expectations it seem largely on CHs ILMN derived reputation and the fact that he also attracted mid-level execs from ILMN. Having said that HiFi does seem to have a growing fan base.