Tuesday, May 21, 2019

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

Monday, May 20, 2019

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

Friday, May 17, 2019

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.

Monday, May 06, 2019

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.

Thursday, May 02, 2019

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. (*)

Wednesday, April 24, 2019

Want to Run An Exciting Sequencing Group? Ginkgo Is Looking for You!

I've awakened from my blogging torpor to point out a really interesting career opportunity for the types who might read this space. Ginkgo Bioworks, one of the leading synthetic biology companies in the world, is looking for someone to run their existing Next Generation Sequencing group. It's a chance to run an energetic high-throughput sequencing group that works on a wide range of projects. And, as you might of guessed from the fact I'm writing about it here, you'd also get to be my boss. I'm hoping many will see that as a feature and not a bug.

Monday, March 25, 2019

Nanosens Publishes Proof-of-Concept for Point-of-Care CNV Diagnostic

Here's a killer technological challenge for anyone: design a scheme to detect vanishingly small concentrations of a valuable analyte in a biological fluid.  The assay must require zero pipetting, work in the field at ambient temperature, generate results quickly, contain positive and negative controls, be usefully precise and accurate, and be usable by personnel with no formal technical training.  Oh, and be dirt cheap as well.

Wednesday, February 20, 2019

Beyond Generations: My Vocabulary for Sequencing Tech

Many writers have attempted to divide Next Generation Sequencing into Second Generation Sequencing and Third Generation Sequencing.  Personally, I think it isn't helpful and just confuses matters.  I'm not the biggest fan of Next Generation Sequencing (NGS) to start with, as like "post-modern architecture" (or heck, "modern architecture") it isn't future-proofed.  Not that I wouldn't take a job with NGS in the title, but still not a favorite.  High Throughput Sequencing feels a little better, but again doesn't leave room for distinguishing growth -- and HTS as an abbreviation is already going to confuse anyone in Biopharma who thinks about High Throughput Screening.  Massively Parallel Sequencing sort of works, but my late father had a real pedantic objection to using "massive" for anything that lacked mass, and while I don't subscribe to that view such uses just don't sit well with me.  Worse, as I'll explain, trying to divide sequencer technologies into Second and Third generations creates more heat and smoke than light.  On a number of Twitter threads I've tried to launch my own terminology, but probably haven't been terribly consistent.  So here is an attempt at that.

Thursday, February 07, 2019

Failing to Fetch An Interesting Result on Dog Oncogene Homologs

An idea for a little exploration occurred to me back at Infinity -- that is 7.5 years ago -- that I've never tried out.  But I never got around to it.  I had some downtime recently  to play around so I finally executed the experiment -- alas, it turns out not to be very interesting.  Still, a negative result is a negative result.

Wednesday, January 30, 2019

Covaris Grabs A Spot on the Liquid Handler Deck

For as long as I can remember, Covaris has been the standard in DNA shearing for high throughput short read sequencing.  Their benchtop units had their quirks -- custom tubes being the foremost -- but they were what everyone else compared to.  In 2013 when the American Society for Human Genetics was in town, the PacBio folks did me a great favor and loaned me an exhibit hall pass.  Multiple companies were offering DNA shearing instruments -- and every one compared themselves against Covaris.  Now they have a new offering, moving the instrument onto a liquid handling robot deck so that it is available for high-throughput workflows.  Covaris invited me down to their Woburn, Massachusetts facility to get a look at the instrument before its formal launch at the SLAS conference

Tuesday, January 29, 2019

Patent Dive: Genapsys

Here's a dangerous statement for me: I actually enjoyed reading some patents recently.  Now, before you get any ideas in your head about suggesting more patents for me to read, let me be clear that these were unusual patents -- they're written to be read! -- and were read under strict conditions. The patents in question are from Genapsys -- found via my good friend Justia.

Monday, January 28, 2019

Metabolic Whac-a-Mole

Derek Lowe summarized a really cool paper back in October.  I've been meaning to grab a copy, but discovered recently that the MIT library no longer has an easy way for outsiders to slip in an use their subscriptions.  So I'm working off his summary, but since this is mostly an excuse for flights of genetic fantasy actually reading the paper would probably just hinder me!

Friday, January 25, 2019

2019 Tech Speculations: Oxford Nanopore

As promised in the last post, I'm segregating out Oxford Nanopore.  Admittedly I tend to cover them relatively closely -- though I never seem to quite finish writing up their conferences -- but at the moment ONT is the only major player in the U.S. research sequencing market not being run out of (or about to be run out of) Illumina HQ.  And I'll be very to the point: ONT has a lot of balls in the air and irons in the fire, but from my point-of-view what matters most is rapid and regular progress on the accuracy front.

Tuesday, January 15, 2019

2019 Sequencing Tech Speculations: Will We Actually See New Entrants?

An astute reader caught a sentence fragment about MGI in last night's Illumina JPM roundup -- the unfortunate evidence of a a mental battle over whether to put any further comments on MGI in an Illumina-centric post. So now I'll sweep that bit into a general post about not-Illumina (and not-Oxford, that will go in yet another).

Monday, January 14, 2019

Illumina JPM Talk

Illumina CEO Francis deSouza delivered his J.P. Morgan Healthcare Conference talk (webcast audio, slides & Q&A audio) a week ago.  I can claim that some of my speculations came true -- just the most boring and obvious ones.  Overall, the presentation was the talk of a confident market leader.

Sunday, January 06, 2019

2019 Sequencing Tech Speculations, Part I: Illumina & MGI

Next week is the J.P. Morgan Healthcare Conference.  It's striking this year the paucity of companies in the genomics space -- Illumina on Mondayat 6:00 EST and MGI on Wednesday at 5:30 EST and Nanostring at 6:30 EST on Wednesday.  Perhaps NVIDIA will say something interesting about their forays into healthcare, such as providing the chops for real time nanopore basecalling, on Thursday at 11:30 EST. There's also some nice polls from Albert Viella on Twitter
and some more Twitter speculation

So, before all the beans are spilled, here's some of the speculations and ponderings I've been entertaining about the sequencing technology field for 2019 for Illumina and MGI.  I'll cover some of the other players in the next few days, but since Illumina is up on Monday that's the priority!

Thursday, January 03, 2019

2019 Resolutions

2019 is upon us; I'm hoping it will be a bit less eventful than 2018.  It wasn't all bad -- I took two trips that delivered scenery I have only right to see once in a lifetime -- but it was essentially bookended by losing my father and a revolution in my workplace.  Mixed in there is the bittersweet pride of seeing one's offspring graduate from high school and proceed on to college.

New Year's resolutions are notoriously difficult to keep -- one is fighting entrenched behaviors -- but bringing in some external pressure might help.  So I'll make my two resolutions for the year very public: that I post here more regularly and that I read more non-fiction books to the end.  And the hope is that you, dear reader, if you meet me, feel free to pointedly inquire about my adherence.  Or hit me via Twitter!