ASHG is ongoing and tonight PacBio has a big party planned, with an unnamed musical guest. Rumors swirl as to what will be announced at that event. But in advance of the meeting, last week PacBio described multiple updates to the Revio platform, an instrument which made its debut two years ago at ASHG. PacBio CEO Christian Henry was kind enough to chat with me last week about the upgrades.
SPRQ
The flashiest announcement is the new SPRQ flowcell chemistry for Revio. SPRQ increases yields without reducing quality, enabling two 20X human genomes to be generated per flowcell for $500 in library prep plus running cost (but that cost not including sample prep or downstream analysis). Of course, once you are multiplexing samples there's opportunity to use the instrument capacity for non-integer numbers of genomes per flowcell, so this could also mean running ten 16X genomes per run or the non triskadecaphobic could pack thirteen 12X human genomes per run. And so forth.
Not only more genomes per flowcell, but both 5mC (in CpG context) and 6mA methylation calling. Henry noted that the 5mC fraction can be a useful indicator of the degree of bacterial contamination of a sample - such as one from saliva (more on this below). PacBio is excited about FiberSeq methods for chromatin accessibility (
which I covered back in the spring) enabled by the 6mA detection.
More data is great, but perhaps equally valuable is lowering the amount of input required. Instead of 2 micrograms of total library, the requirement is now only 500 nanograms. And that is total library - if multiplexing two samples then each must yield only 250 nanograms. Nothing has changed in the library prep - which must yield a sigh of relief from companies such as
Volta working on PacBio compatible library automation.
On the technical side, SPRQ hosts a new polymerase and new buffers, yielding subreads which are about 2 phred points higher in accuracy. That doesn't sound like much, but anyone who has worked with noisy reads will grasp how just a small improvement in accuracy greatly eases the alignment and other steps involved in the CCS and DeepConsensus algorithms. That will also mean that subread sets that previously wouldn't yield high quality data now will. PacBio also changed how the sample is applied to the flowcell, enabling more of the ZMWs to be productively loaded (this is covered
in more detail by Nava Whiteford). So better raw data from more ZMWs to yield an overall increase in HiFi data yield.
Along with all this improvement, Revio is dropping in list price from $779K to $599K - or similar to what the list used to be on a Sequel IIe.
Ready for Their Spit Take
Back in 2021 PacBio acquired sample prep maker Circulomics. The Circulomics Nanobind PanDNA kit has been a workhorse for many sample types - but not saliva. Now saliva joins the list of sample types, opening up much easier access to human samples, with a 500 microliter sample requirement. I haven't done a spit test myself - but have swabbed each of my dogs. Coupled with SPRQ's lesser input requirement - and the 5mC calling for quality control - Revio should become even more popular for human genetics research
Head in the Cloud
For years it has been an option to process your PacBio data in the cloud, if you were willing to learn the intricate geekery of setting up and maintaining cloud compute resources. PacBio will soon (Q1) be rolling out SMRT Link Cloud, usable with any S3 compatible cloud (e.g. AWS, GCP or Azure) compute provider. The software is free; users are responsible for paying their own cloud costs. Henry suggested that in the future there might be subscription-based advanced analysis tools, but that's not a given. SMRT Link Cloud is also intended to interface cleanly with analysis partners such as GeneYX or DNANexus. Or perhaps ultimately from some lab that isn't yet using HiFi - Henry believes "our best ideas will come from our customers"
Closing
As noted, there is a big event tonight with many rumors surrounding it (alas, the grim reaper has prevented a proper
Fleetwood Mac from being the musical headliners). If you want to start any rumors about whether Christian & I discussed anything beyond what is above, you have about half a day to propagate them.
