The Genius of Plongle

I noted in my roundup of Oxford Nanopore technical announcements that I loved the Plongle concept.  This is really both a new application-specific integrated circuit (ASIC) and using it to build a 96-well sequencer.  Let me expand on what there is to love.

ONT's Horrid Data Storage Folly

In the coverage of ONT's announcements at London Calling, I specifically left out one of Clive's Skunk Works projects.  This would be a device to use nanopores to write digital information.  I'll give him points for creativity, but the reason I held this for here is I truly and sincerely hate the concept and didn't want my vitriol to distract within the other piece.  But here I will let loose.

ONT's London Calling Announcements, Pass One

The annual big Clive Brown London Calling talk had a twist this year  Brown introduced a set of senior lieutenants at Oxford Nanopore and then tacked on a few "and one more thing" moments at the end.  If you're looking for the TL;DR version from me, it is that there were a lot of sensible but non-Earth shattering updates from the team followed by Clive updating on one prior crazy idea and throwing out two more -- one of which I love and the other I believe should be thrown out posthaste.

Nanopore's Long DNA Paradox

The first half day of London Calling has already delivered the usual mix of scientific excitement.  The prospect of lives, particularly those of children, en masse by delivering precision oncology broadly across sub-Saharan Africa.  Dizzying levels of alternative splicing in a key brain ion channel.  RNA modifications in great numbers.  That one was also gratifying as it was commented that even without a basecaller, modified bases can be be suggested by higher error rates around a particular motif.  Around 2015 or so I noted in the Nanopore Community post that error rates went up around GATC sites in E.coli, the target of Dam methylase.  Protein tags read by the current nanopore scheme. Tonight we get Clive and company performing their usual razzle-dazzle of product announcements; one person pointed out to me a possible angle I failed to include in my laundry list is the raising of the speed limit from 450 to perhaps 1000 bases per second.  But another omission was front-and-center in the plant genomics sub-session I attended and could be called the central paradox of the current state of nanopore sequencing:  pores are great for long DNA but long DNA is not great for pores.

Care to Pore Over My Laundry List?

London Calling is this week, so get ready for lots of Oxford Nanopore in my Twitter channel and if I'm on the ball, in this space.  ONT has made a number of releases and updates and there have been other developments within the nanopore ecosystem which I've failed to report.  Here, in not terribly organized fashion, is a laundry list of things I'm thinking about going into the meeting

Mass Recoded E.coli Genome Not Tripped Up By Programmed Frameshifts

There's a paper this week in Nature announcing an E.coli genome which has had two serine codons (UCA, UCG) and one stop codon (UAG) removed from usage.  It's a major work on synthetic biology and represents the largest designed sequence ever built.  In contrast to Craig Venter's early effort, which moved a synthesized genome into a cellular ghost of a natural bacterium, this one replaced the native E.coli genome in stages -- Escherichia theseusshipii would be a good name for the new strain. But is the genome quite what is advertised? Following up on a pair posts from Sandeep Chakraborty showing remaining UCA, UCG codons and UAG codons in a bunch of typical genes, I decided to look for a trickier set of possibilities to overloop -- and by luck or care the Nature paper got these.  Just to put one gripe front-and-center, the group deposited in Genbank the reduced genome version of E.coli they started with, but not the recoded genome, which is in the supplementary material

My Career's Double Slit Experiment (or, A Funny Thing Happened on the Way to the Drydock)

When I announced recently that I had moved over to Ginkgo Bioworks, I was compelled to leave out an important part of that story.  Indeed, by just focusing on the (still open) position of NGS Head, I could avoid the sticky subject of how exactly I ended up there.  Today the press release finally went out and the fact that Warp Drive's genome mining business is now owned by Ginkgo is public (covered nicely by Amy Feldman in Forbes).  But in the spirit of my periodic public coverage of my own journey, here is some of the rest of the story.

Genapsys' Base Caller: Mysterious, But Not Ideal?

When I wrote about Genapsys' pre-print on their sequencing system the other night, I intended that to be the last I wrote until some major news from them.  But after launching that into the great Internet ether,  I found myself lying awake wondering if a very simple idea had any merit.  Painfully simple -- I almost didn't pursue it because it was so simple and obvious.  But, it turns out it appears to have merit -- there may be an obvious route to improving the accuracy of Genapsys' basecalling on homopolymers.  And that also took me into ground I've thought about before -- going back to my first year at Codon Devices over a decade ago -- on the challenge of modeling sequence quality.

Poking at Genapsys Preprint

Genapsys is continuing down the path of pre-launch information, most recently releasing a pre-print.  I'm looking at this pre-print critically and unfortunately turning into a bit of Reviewer #3.  Not that anything is fatal and pre-publication review is a key value to pre-prints. If I were an actual reviewer I'd be writing mostly the same things and covering more vertebrate species than they sequenced (a human exome panel  was included, though most samples were bacterial) -- I'd grouse about a missing figure (which I've provided), carp about critical details not provided and beef over a public data deposit that doesn't really line up with the unqualified claim made in the paper. (*)