Tuesday, October 26, 2021

A Look at Two HiFi Polisher Preprints

PacBio has made its reputation delivering very high accuracy long reads, which they have branded HiFi. These are based on their circular consensus technology: each template DNA molecule is converted into a single continuous circle of DNA which can be read in a rolling circle reaction.  The "movie" is converted to raw base calls and the adapters are clipped out, leaving "subreads" which can be aligned together to generate a consensus (CCS) read.  With many passes over the same molecule and its complement, the relatively high (~15%) error rate of the raw data can be brought down substantially using an HMM-based scheme.  PacBio calls reads HiFi at 1% error rate, but their model calls overall quality for reads and it can keep getting better from there.  Homopolymers still bedevil the technology, though not like they once did and it turns out there is at least one more systematic error class.  Consensus building is a powerful way to cut through error.  But could you do better?  Two recent preprints from large tech companies, with PacBio co-authors, apply deep learning to this problem and each comes up with the astounding result that they can do a bit over 40% better.  

Wednesday, August 04, 2021

PacBio Pulls Down Circulomics

I was on vacation early this week when the news broke that PacBio has acquired HMW DNA solid phase extraction kit maker Circulomics -- the kind of vacation that I need where the scenery is gorgeous and the internet access terrible.  Where solid phase means monumental slabs of granite with diabase intrusions being attacked by a high salt liquid phase.  Where I actually sighted Atlantic Puffins and didn't once think about sequencing their genomes ('til now!).  But now I'm back to work and genomics.

Tuesday, July 20, 2021

PacBio Enters a Binding Agreement to Acquire Omniome

Pacific Biosciences announced today that they are slurping up short read sequencer startup Omniome for around $800M.  Omniome has been developing an interesting clonal read technology.  On the conflict-of-interest side, many years ago (and I think an entire management team different) Omniome treated myself and my family to a weekend in San Diego (it was my son's birthday weekend) so I could look at their technology back then -- my NDA has expired but so has most of my memory of what I saw at that meeting!  Also the periodic reminder that PacBio Christian Henry sits on the board of my employer, though we haven't met. Simon Barnett of ARK Investments (which is a major holder of PacBio stock) has a very nice explainer on the Omniome Sequencing-By-Binding (SBB) chemistry and his bullish perspective on the acquisition and there is a proof-of-concept publication of the technology. I'll briefly explain the tech and then outline my somewhat more bearish view. It's also interesting to note that the FTC's actions on Illumina-PacBio and Illumina-Grail have analysts jumpy about this acquisition attempt.

Tuesday, June 29, 2021

ONT Sketches Paths to Long, Selective, Accurate Sequencing

Some sort of summary of London Calling in this space is grossly overdue after getting caught by multiple work firedrills and then several recursive rounds of procrastination. I'm not going to attempt to cover all the company announcements.  I'm going to focus on a cluster of announcements that show a long range vision of inexpensive sequencing consisting of very accurate, very long reads.  Well, a cluster of visions -- some parts can be mixed and matched and others cannot. This should be a prospect to grab the attention of any current or aspiring ONT competitors.  Now before I'm accused of being a gullible shill for Oxford, I want to make it clear I think that running the table on these will be technically difficult and is many years in the future.  But  even if Oxford manages some of these but not all, they would substantially upgrade their platform.

Wednesday, June 02, 2021

New Clinical Human Genome Speed Record

I proposed last year that there should be a regular racing event for human genomics.  The only real competitor in is this interesting race seems to be Steven Kingsmore's group at Rady Children's Hospital.  I was sent an embargoed press release from Illumina about a new record by that group, which clocks in at 13.5 hours from patient sample to clinical report. A New England Journal of Medicine paper (hence the embargo, ending just before I post this) reports on the advance but wasn't in the packet I received.

Tuesday, May 25, 2021

Matt Meselson Needs a Biographer!

Yesterday was Matt Meselson's 91st birthday.  I have only met him a few times and he wouldn't know me from Adam, but he is a particularly interesting individual I've had the good fortune to converse with.  I'm putting out a plea now for a skilled biographer to write his life, because it certainly has been an interesting and impactful one, with scientific work stretching from the early beginnings of molecular genetics to a preprint just recently posted on BioRxiv.

Thursday, May 20, 2021

My Latest London Calling Thoughts

The title really says it -- London Calling has actually already begun and here I am pretending to write a "before the conference" piece.  Of course, since everything is virtual again this year I can actually do this since I haven't watched anything yet nor have seen any tweets -- and the big technology announcement section isn't for a few hours so I have loads of time to write!  Sadly, nor have I gone and looked at what I've written before.  Nor have I defended these two days very well - my schedule is cluttered with meetings and appointments.  So I haven't prepared in any way, shape or form -- but here goes some thoughts.