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?

Two Museums Guaranteed to Fluor You

I've been horribly neglecting this space for an extended period.  Contributors to that include a TNG eclosing from high school, ferrying grandparents, a milestone (or is it millstone?) birthday and a 10 day vacation with poor Internet service.  Oh yeah, another one of those starts Thursday.  Then there's keeping the genome factory going -- at times I feel like a worker in Fritz Lang's Metropolis.  But someone even noticed and emailed me today whether this hiatus would end, which is beyond reason enough to get going.  But tonight's entry has nothing really to do with biology or genomics, but rather hearkens back to the first science I fell for.

LC2018: VolTRAX

In my preview ahead of London Calling, I suggested that VolTRAX is a device that still hasn't found its raison d'etre.  With the meeting, the device officially pre-launched and the company is now taking pre-orders for delivery in the Fall.  And it still feels like a device which hasn't yet found its purpose, though Clive Brown presented a dazzling (if perhaps distant) vision of where VolTRAX might go.

LC2018: Flongle, Ubik-a-something and Metricoin

London Calling has been over for nearly three weeks.  I originally wanted to write up at least something after the first night, but fatigue overcame me and I didn't get anything useful put together.  And then travel and more fatigue set in.  But beyond that and the usual temptation to procrastinate, there is the challenge of forming a coherent narrative from all the different threads at the meeting.  There's all the Oxford Nanopore official announcements and then various user presentation tidbits.  After several failed mental attempts to compose a big picture take on everything, I've decided to try to write a series (number yet indeterminate) of posts that will focus of various axes of the meeting.  Hopefully they won't be to redundant -- or self-contradictory -- and that by following one particular thread I can actually condense some coherent thoughts.  This first such thread starts with Flongle.

Miscellaneous & Disorderly Thoughts on the Eve of London Calling

It's the night before London Calling. I hope to post Thursday, but an after-meeting report won’t be until nest week - I must dash on Friday fir a slightly insane/exhilarating routing to meet my family in Florida for the holiday weekend. Exhilarating as I will have a layover in one of the ancient capitals of Europe, Lisbon, which I’ve never visited. Insane, because it’s a 12 hour overnight layover. Anyway, between the challenge of covering Oxford Nanopore's expanding reach of products and applications and being sleep-addled from taking the redeye flight I'm going to throw out a bunch of thoughts without really trying to fuse them into a coherent narrative.

Should PentaSaturn Buy An iSeq: A Hypothetical Scenario Illustrating Platform Picking

Editorial note: I wrote this in early January, then planned to slot it in after some other items.  Then life knocked me upside the head, then AGBT came along and then it was forgotten.  Once I remember it, I fretted it had gone stale. But I had put a lot of effort into it and really nothing has changed with regard to iSeq, other than it should be shipping now.  Besides, this week is London Calling and so having an Illumina-centric piece could be a bit of useful balance.  So, for your consideration:

Some of the online discussion around this January's iSeq announcement, springing from my piece or elsewhere, explores how the iSeq fits into the sequencing landscape.  In particular, how does it fit in with Illumina's existing MiniSeq and MiSeq and how does it go against Oxford Nanopore's MinION.  For example, in Matthew Herper's Forbes piece, genomics maven Elaine Mardis compares iSeq unfavorably to MiSeq in terms of cost-per-basepair.  I'm a huge believer in fitting sequencing to ones scientific and practical realities and not the other way 'round: no one platform quite fits all situations nor do even the same metrics fit all situations.  So in this piece, I'm going to illustrate what I believe is a plausible scenario in which iSeq would make sense.  Now, I have designed this to play to iSeq's characteristics and very realistically have many dials which I could turn to go in another direction.  Which I will try to note as I go along.

PromethION Racing: A Call To The Post

I was at a get-together yesterday for bioinformatics folks associated with Third Rock Ventures companies at a local pub.  The organizer, who I've known for a number of years, was introducing me with the pleasant "Keith writes a nice blog" -- but then the barb "but he hasn't posted in a while". Ouch! But it hurts because it's true; too many excuses to not write and far too many half-baked ideas and interviews that should be out (or worse, a nearly complete post).  Since it is May, which in the U.S. is bookended by iconic racing events, I'd like to trot out an idea that has been idling for a while: PromethION Racing.

Mission Bio Launches Custom Panels

Back in October I covered the launch of Mission Bio's single cell platform, Tapestri.  Tapestri is a microfluidic platform which encapsulates cells and sets of barcoded primers into droplets, lyses the cells within the droplets and executes PCR on the released DNA.  Mission initially targeted hematologic cells, since they do not require disaggregation, and offered a standard panel of primes.  Around the time of AGBT, Mission launched a custom panel option and took the time to sit down with me.  Now with AACR, Mission has announced placing Tapestri at multiple major cancer centers: the NCI, Mt. Sinai, MD Anderson, Memorial Sloan Kettering, St. Jude's, UCSF, U Penn and Washington University.

A Small Rampage Over STAT's Movie Piece

A movie opened this weekend which, by all prior evidence and new reviews, is unbelievably silly but destined to rake in the bucks. Rampage is very loosely - as if it could be another way - based on a video arcade game. The original game’s backstory had a mysterious ray transforming people into monsters, but the movie has changed that to CRISPR. So STAT had a piece which, to my great disappointment, gave the movie’s science a near pass in a piece featuring two writers chatting . . (Note: this post has mild spoilers, though if you've seen the trailers they give almost all of this away).

A Most Unfortunate Sequencing Error

If you are in the sequencing business, you'd like to get things right.  But sequencing is a form of measurement and measurement has error.  No matter how diligent and committed you are, sometimes the data doesn't break your way.  Mick Watson has a set of posts and a preprint illustrating quality issues in many deposited bacterial genomes.  Some of those are bad luck and some of those are from complacency.  Some errors radically affect biological interpretation and some don't. I'm going to detail here one of the worst cases of bad luck I've seen, where relatively small errors sat undetected for over a decade and triggered some published head scratching over their erroneous implications. So let's look at the rap sheet of this error.

A Morning Visit to SeqLL

I've written in the past about SeqLL, the company which purchased all of the hard assets from Helicos after the latter's demise.  At the end of last year, CEO Elizabeth Reczek invited me to stop by for a visit and so I spent a morning having a frank discussion with Dr. Reczek and Director of Sales Lee Dalton and also was treated to a tour of their facilities.

PromethION: Straining at the Starting Gate

Due to the usual time conflicts, I've only watched bits-and-pieces of the Winter Olympics from South Korea. Which is unfortunate, as I do enjoy observing many of these events as so many combine grace, power and finesse.  In the various timed events, the competitors can be seen tightly wound, ready to spring out at the crack of the start.  Increasingly, that is how Oxford Nanopore's PromethION looks: a superb performer ready to bolt away.

AGBT: It Ain't Over 'til the Tattoo Wears Off

AGBT officially ended on Thursday night with a space-themed party, but I have a bunch of notes from interviews with company representatives and even a few notes from sessions.  So be prepared for a string of further AGBT reports.  This dispatch will have some overall thoughts as well as some notes on the possible return of AGBT to Marco Island next year.  I also want to mention two good AGBT 2018 summaries, one from Dale Yuzuki and another from Decibio's Stephane Budel.

newly applied

AGBT: BioNano Launches New Labeling Approach

AS AGBT opened, optical mapping company BioNano Genomics announced a new scheme for labeling genomic DNA inputs which substantially improves performance.  Sven Bocklandt from the company sat down with me yesterday to walk through the new Direct Labeling

AGBT: Twist Biosciences Launches Sequence Capture Product

Twist Biosciences today launched a new product into the sequence capture space.  CEO Emily Leproust was presenting to the Gold Sponsor workshop as I started writing this, but she also sat down with me yesterday to preview the new offering for targeted sequencing.

AGBT: 10X Previews Three New Single Cell Applications

I spent breakfast with 10X Genomic's Michael Schnall-Levin and two of his 10X colleagues gave me a sneak peak at three new single cell products they are rolling out at the workshop I'm typing away at now.  These enable measuring protein targets of antibodies, mapping out accessible chromatin regions with ATAC-Seq, and mapping copy number variants (CNVs) at single cell resolution.  All use the existing Chromium Controller instrument.

AGBT Swag Bag

Today at AGBT is light on the science talks; the afternoon is free for lazing around the resort complex -- or for swimming laps in the lazy river (which makes it a not-so-lazy-river). I can only manage downstream; upstream is an aquatic treadmill.  A key task on Day 1 is to pick up one's registration materials.  At one conference I failed to do this promptly and discovered to my dismay that the desk wasn't open during the opening reception slash poster session -- so despite being a speaker I had to sneak into the room via a side door!  Registering means picking one's meal pass -- I took the temporary tattoo over the wristband option -- and grabbing the vaunted AGBT backpack.

AGBT 2018: It's Great to Be Back

All sorts of scheduling snafus have kept me away the past three years. So this time around, I vowed to go and made sure my calendar stayed clear. So clear, I forgot to put a reminder down to actually register for the event. Luckily, there were slots still available when I put my flier in.

Brown Webcast Note: Corrections and Expansions

After I post something, there's almost always something I realize I left out.  In my piece on Clive Brown's webcast of ONT improvements, not only did I forget a few key details but my wording led to some unfortunate confusion, as judged by a comment.  Someone took me up on my idea on how detecting large fragments during a run might work -- and showed it doesn't pan out (which Clive Brown confirmed).  And to top things off, a BioRxiv preprint showed up that exactly covered something I alluded to.

February 2018 Clive Brown Webcast Notes

Clive Brown's webcasts are always entertaining, and even the 6am Eastern Time start for Thursday's didn't hinder that aspect -- though I am thankful I'm not on the U.S. West Coast because I really don't function at 4am.  Even at 6am, I was frequently shutting off my iPad screen or exiting the presentation, as screenshots on iOS involve simultaneously pressing Power and Home keys.  At that hour, my never great fine motor skills just aren't reliable.  Hopefully I won't make the dog's breakfast of this, as that's usually all I'm good for processing at that hour!

Still, lots of updates and promises as well as a number of "wait until London Calling" teasers.  Just to get this out of the way, I'm going to report the launch dates that Oxford mentioned -- anyone in this space should know that Oxford is very good at delivering what they promise, but not very good at delivering when they promise.  You can also find notes by David Eccles to check me against or watch the presentation recording from ONT.

Oxford Nanopore Outlook 2018

I'm behind on these posts.  My usual foibles were largely responsible for a while, but then I had the major (and sad) family issue that has kept me off balance for  two weeks. Someday I may write about that, but for now back to the major sequencing vendors.  Though with Oxford Nanopore, the problem is where to start?  But now is the time to get moving, both since Oxford's Clive Brown will be webcasting an update on Thursday and I'll be at AGBT next week and expect to be busy with news flow from that event. Clive's webcast is titled "sub-$1000 human genomes on Nanopore (and other goodies for H1 2018), so expect quite a casserole of tempting updates.  Certainly it is enough to get me to try to be fully mentally awake at 6 am, something that does not come naturally.

Fingerprints on Jupiter

I had hoped to mark my father's 93rd birthday today in my usual way, a call home to exchange well wishes and update him on our goings-on.  But two weeks ago he entered the hospital for what turned out to be a final visit, so instead I am writing this.

PacBio Outlook 2018

Well, I didn't exactly get my Pacific Biosciences preview out before their J.P. Morgan presentation.  Luckily, the slides for that primarily projected financials and touted their successes -- and didn't drop any major platform announcements in -- so I didn't miss out.  PacBio's position is important and worth reviewing, even if it doesn't change much.

iSeq!

Illumina CEO Francis deSouza's J.P. Morgan Presentation did not disappoint.  While humdrum financials and touting market dominance and areas of future growth came first, then came the big Firefly announcement (with a name change to iSeq 100)  -- and then after another short spell of reviewing the latest Nextera chemistry came a smaller bombshell -- Illumina is partnering with former arch-rival Thermo Fisher (nee Life Technologies nee Applied Biosystems) to move the AmpliSeq multiplex PCR technology over to the Illumina platform.

Illumina Outlook II: The Fleet

In my prior installment I looked at Firefly, now clearly a working instrument.  Now I'll take a peak at the rest of the Illumina fleet.

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.

Remembering 2017's Losses

A new year beckons and with it a burst of enthusiasm for writing.  Which also means combing through post ideas from last year that never quite were completed -- some as stubs or at least headlines.  But before tackling the new, I feel I need to tackle some personal losses in 2017.