PacBio: $300 Genome Via Chemistry Update

ASHG is here in Boston, just down the street from Ginkgo's HQ.  I'm in a new role in Ginkgo Automation, trying to convince the NGS world that our automation platform is the bee's knees.  So excellent timing.  In advance of the meeting I was able to grab 30 minutes of PacBio CEO Christian Henry's time - last time I saw him he was fresh out of the legendary midnight AGBT  ILMN vs. PACB doubles beer pong match.  Christian gave me a heads up on some of the product news that hit the wires a bit earlier this morning. At the top of that is a new version of the core chemistry, SPRQ-Nx, which boosts yields 10-15% as well as the official launch of flowcell reuse.

SPRQ-Nx will launch initially for Revio, but Henry promised it will come to the benchtop Vega sequencer next year as well.  In addition to the throughput boost, 5-hydroxymethyl cytosine calling is fully enabled using the onboard compute.  

Complementary to the new chemistry is the reuse of SMRT cells on Revio, which is fully automated.  This allows multiple loads of library onto a flowcell - initially two or three - allowing far more output.  Since the flowcell is an expensive bit of precision engineered hardware, this will allow very favorable economics which PacBio is splitting between themselves and users.  With both SPRQ-Nx and flowcell reuse, the price per human genome WGS equivalent will drop to the $300-$350 range - the lower number obtained by maximizing flowcell efficiency.  Since PacBio is gaining improved gross margins per basepair and the lower price would be expected to drive greater usage and therefore revenue pull-through, this should improve PacBio's financials - though the gloomy situation in both industrial and academic biotech continues to cast a dark shadow.  Henry noted that in Europe PacBio is seeing year-over-year growth of around 50%, so there can be bright spots if one gazes beyond US borders.  Beta release will be in November, with a cautious ramp-up to full distribution by mid-2026.

Of course, PacBio HiFi reads aren't just for human genomes.  There's all sorts of great uses for metagenomics and synthetic biology, and Henry sees opportunity in the AI push that dominates early biotech funding these days.

PacBio is also expanding the PureTarget capture approach; version 2.0 features 96 barcodes and automation support for several leading platforms.  Multiple major diagnostic sequencing providers have adopted PureTarget and are developing Laboratory Developed Tests (LDTs) - which are rebounding after the FDA's effort to clamp down on LDTs appears to have been completely stymied in the courts.

PacBio also is featured in multiple ASHG posters - searching for "PacBio", "HiFi" and "Revio" easily found 11 and I suspect other posters are hiding under 'long read" in their abstract.  Henry mentioned a WashU study which has examined methylation in 7800 individuals - the size of HiFi projects is getting big! A large Korean pangenome and genome graph effort using HiFi is also seeing the spotlight.  There's also posters on improving diagnostic yield in rare disease work.

How much lower can PacBio push the price of a human genome?  Henry thinks $100 is not an absurd goal, but it will take some time.  Already with SPRQ-Nx genomes priced essentially the same as a standard short read genome on Element AVITI or Illumina NovaSeq X, the perennial question of "why bother with short reads for WGS" becomes increasingly pointed.  Illumina's response is Constellation - a cool technology that I'll try to dive into after reading their slew of posters.  But all indicators suggest Constellation will be more expensive than SPRQ-Nx with flowcell reuse, as there is no sample indexing and so each sample requires a dedicated lane on a 10B flowcell.  

The meeting hasn't even begun, and I'm pitting sequencers against each other and SPRQing conflict!  Let the games begin!

[2025-10-14 12:30 EDT fixed SPRQ-Hq to SPRQ-Hx in one case]