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.

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.

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

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.

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!

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.

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).

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.

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

What would you like @illumina to announce at #JMP2019 ? https://t.co/TDn5J0glhi part 2

— Albert Vilella (@AlbertVilella) January 5, 2019

and some more Twitter speculation

Predictions for @Illumina #JPM2019. Besides PacBio news, expecting NovaSeq SP 2x250. Any longer S4 kit or potential S5 would require upgraded onboard storage. Really hoping no new NovaSeq system.

— CAT at UCSF (@CAT_UCSF) January 4, 2019

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!

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!

An Unfortunate Master Class in Poor Plotting

I hope my admiration for Pacific Biosciences intellectual acumen was clear in my post on the acquisition by Illumina, because now I'm going to be a rabid crab over a webinar they aired yesterday.  I take telling scientific stories seriously and an important part of telling such stories is displaying data well.  I'm a perfectionist in this department by intention, but not always by execution -- I'm constantly reanalyzing my plots and diagrams for errors and cringing when I find them.  The webinar is trying to extol the value of the latest developments in the SMRT platform, but the data graphs often actively fight against any understanding or excitement.

Flappie vs. Albacore via Counterr

I'm going to go through some analysis of Oxford Nanopore basecalling, running some quick comparisons using a freely-available tool called counterr which was announced at the Nanopore Community Meeting two weeks ago.  Counterr was developed by Day Zero Diagnostics, a startup I advise -- though in announcing yet again my COI I will stress I don't get paid to help give away software!  This is just a small bit of analysis; nothing as comprehensive as Ryan Wick's ongoing analysis with a ready-to-submit preprint masquerading as a README file.

Nanopore Community Meeting 2018: The Clive Report

Given it's late and I just dashed through a classic San Francisco downpour, I'm going to mostly stick to covering Clive Brown's talk tonight.  Within it there were a number of announcements, and for anyone following this space I get to point out things I've proposed in the past that are moving to fruition as well as recent statements I made that were quite erroneous.

Also note that tweets during his talk have been collected by ONT into a Twitter Moment

A Few Things Before Nanopore Community Meeting Begins

Nanopore Community Meeting begins within the hour.  San Francisco is spectacular as ever -- Alcatraz Island disappearing into the fog as I fiddled with camera settings, the spectacular Bay Bridge spans are visible from the the breakfast area and I even got to see some notable locals on my walk over from the hotel

If this crowd doesn’t get a move on, they’re going to miss #nanoporeconf breakfast pic.twitter.com/rFwfGdQTit

— Keith Robison (@OmicsOmicsBlog) November 28, 2018

Hans Jansen was kind enough to remind me by tweet of a couple of missed topics in my preview piece.  So let's cover them!.

Nanopore Community Meeting 2018 Preview

Okay, now that I'm done venting -- for now -- about ONT's customer service experience  (well, almost done -- they sent me the same damn letter they sent my colleague -- why were they several hours apart???) -- let's move on to the Nanopore Community Meeting.  Technically it started today with the training session, but I'm not heading out until tonight.  At the first one of these in NYC Oxford tried to avoid making any announcements, but they seem to now like having two major focus times a year sometimes supplemented with Clive Brown webinars in between.  Here are some

How Not Do Think Like A Customer: Examples from ONT and AMZN

I'd planned today to use some downtime to write up a preview of the Nanopore Community Meeting which I am attending tomorrow and Thursday.  I might still do that, but the same organization just engaged in the sort of customer engagement that drives me batty (yeah, twisting the lion's tail before entering their den -- smart move or what?) and it reminded me of another lousy experience I had recently with a very prominent company: Amazon.

Failure: The Real Secret Sauce of Engineering

I took one swing at Vijay Pande's overly rosy piece on applying engineering methods to biology and medicine and similar minded efforts were published by Ash Jogalekar at Curious Wavefunction and Derek Lowe at In The Pipeline. Perhaps I shouldn't make another go, but it is a new excuse to explore an old fascination of mine.  Pande's subhead was "Billion-dollar bridges rarely fail -- whereas billion-dollar drug failures are routine".  I can't argue that.  Actually, it would seem from an informal search that billion dollar bridges are actually much rarer than billion dollar drug development programs.  Obviously they exist -- I've traversed the new Tappan Zee Bridge which came in over $3B.  On the other hand, a second crossing at perhaps the most notorious spot in bridge engineering history, the Tacoma Narrows, was built earlier in this century for only $0.8B.  What I wish to explore are the failures of bridges and other structures of any cost, as it is the analysis of failures that frequently propels engineering forwards.  That analysis is enabled by the relative simplicity of human engineering and the artifacts it uses and creates.  Conversely, analyzing the failure of new drugs is nothing like that.

No, the Groves Fallacy Can't be Retired Yet

Vijay Pande has a thought-provoking piece in Scientific American on the Groves Fallacy, though in the end I'm afraid mostly what he provokes in me is the thought that he's in most cases pretty far off base. Titled "How to Engineer Biology", he claims that the Grove Fallacy -- the idea that biology can't be tamed by engineering -- is quickly being put to rest.  And Pande isn't some naive Silicon Valley type, but a professor at Stanford whose lab works in experimental biology.  So he has some street cred -- but that doesn't mean he isn't mostly wrong.

Illumina Buys PacBio: More Thoughts

Illumina surprised pretty much everyone in the genomics community by announcing the purchase of Pacific Biosciences.  I had spent Thursday deep in the weeds of a combined PacBio-ONT-Illumina dataset, so was caught completely by surprise on my commute home by an email asking for my comment.  If you do want to hear hot takes on it from myself and AllSeq's Shawn Baker, Theral Timpson over at Mendelspod interviewed us that night.  There has of course been much discussion of the deal and tributes.   I've had the weekend to ponder things, and here are some somewhat better thought out and detailed comments -- though I don't believe I've retreated from any of the themes in the podcast.  I've grouped the thoughts into a few themes.

You Can Be Impatient Running MInIONs, But Not Feeding Them

Yes, it's been way too long since I wrote here.  Even longer since I did so with any regularity.  There was always some list of things draining my time and energy.  But I resolved this week to get back on the horse -- and that was even before today's bit of dilithium news. In particular, in one twenty-four hour span three different people remarked on the prolonged hiatus -- a professional contact, a commenter on the blog and finally some very cutting remarks from Draco (aka TNG).  And what better way to get going again but to kvetch about Oxford Nanopore's supply chain model?