Illumina 2018 Preview I: Firefly

Time to start gazing into my cloudy liquid crystal ball and attempt to see what will happen in the sequencing world in 2018.  J.P. Morgan is next week, which puts a time box on getting predictions out. One thing I see on both my personal and blogging horizon are flying creatures bearing light.  On the local front, TNG has decided to head this fall to the City of Brotherly Love to learn to fly and breath flame.  But in the sequencing world -- well, I'm going to need to pack a huge Ball jar for my trip to AGBT this year, as I plan to hunt out a Firefly.
Illumina announced Project Firefly two years ago at J.P. Morgan and then reiterated at last year's J.P. Morgan a goal of launching the instrument by the end of 2017.  While full launch hasn't happened, Chris Mason tweeted out just before Christmas a first public sighting of the critter.

First run on the new @illumina Firefly sequencer looks great! 6M 151x151 PF reads, 1.8GBases, >99.8% accuracy in 16 hours. Santa came with SBS candy in a CMOS wrapper this year. pic.twitter.com/TeAYny60cJ

— Christopher Mason (@mason_lab) December 21, 2017

 It will be interesting to see details on how closely the instrument follows the original announcement.  To recap, from my coverage linked above, the idea was to use a variant Illumina's terminator chemistry but detect base additions electronically rather than optically.  A companion box was supposed to automate library prep,  but that announcement was long before Illumina threw in the towel on the NeoPrep microfluidic library prep instrument last year. It also isn't clear whether Chris' timing includes the library prep or is just for sequencing chemistry.  Firefly was originally announced as a $30K instrument; whether that price is still a go is another key point.  Assessing any data quirks of the new chemistry must await the availability of large datasets generated from known samples -- ideally a mix of Bacillus subtilis (low GC), Escherichia coli (mid GC) and Streptomyces coelicolor (high GC).

Many would argue that the world is awash in excess Illumina capacity (e.g. see this recent blogpost by an interesting new commenter on the sequencing world).  The recent launch of the S4 chip for NovaSeq certainly has boosted capacities of the big centers further (more on this in my next installment).  Understanding a role for Firefly really needs to await final pricing for the instrument and kits, but I would expect this would be popular with select startups that want quick access to sequence (sometimes FedEx is just too damn slow) but have project sizes that fit the box.  For example, assuming the duplication rate isn't painful, 1.8Gbases is sufficient for 100X coverage of about three E.coli-class genomes or two Streptomyces.  In the synthetic biology space, you could sequence perhaps a plate of small BACs with that capacity, assuming you do a decent job of host background removal upstream of library prep.  In turn, that could drive demand for high-multiplex library kits such as  seqWell plexWell and iGenomX RipTide.  Academic groups that like their data fast might also be homes for such as device, particularly if they are developing assays or validating constructs and trying to drive a fast design-build-test cycle.

A key question is where the price per basepair finally falls out -- will Illumina dare risk cannibalizing the markets for MiSeq and MiniSeq in order to snag market share.  MiniSeq is particularly close in performance -- Firefly delivers about 80% as much 2x150 data in a similar amount of time.  And of course, if your application can ride out the sequence quality issues of Oxford Nanopore, that $30K pricetag would buy and awful lot of MinION flowcells and practiced users can get 2Gbases of long read data in a few hours, including library prep.

Next time I'll review the remaining lineup of Illumina sequencing instruments.  After that, I'd better get to PacBio before J.P. Morgan rolls in.  Then onto Oxford!