June 2015: Busting Out All Over with Genomics Technology

This month I again entered the prime of my life, though next year my programming brother points out that next year I (and the first Apollo manned missions) hit the big 30.  Beyond my personal milestone, it's been a busy last couple of weeks on the genomics technology front. Despite a lack of conferences or other traditional venues, big news has poured out from Pacific Biosciences, BioNano Genomics, Genapsys, BGI (which had another announcement earlier in the month), 10X Genomics and a pair from Oxford Nanopore.

BGI Unveils a Sequencing Factory to Go

When I was in George Church's lab, he submitted a grant proposal (which, alas, was not funded) for a sequencing factory to generate one megabase of data per day.  In those days that was an ambitious goal, and the plan would have truly been on a factory scale, with a large workforce and an assembly line of stages to yield the final product of data.

Is Illumina Serious About an Alternate Chemistry for the Rapid Amplicon Market?

Back in January, at the end of my post on Illumina's new machine lineup I speculated whether Illumina might see a niche for a lower cost, lower throughput sequencing system that would slot below the MiSeq in their lineup.  Such an instrument, I posited, might go after applications in biosurveilance and diagnostics where relatively small amounts of data are needed quickly. I speculated that perhaps a smaller instrument with less expensive optics could compete in this arena, which is heating up due to Oxford Nanopore and the growing acceptance of DNA-based diagnostics.  As luck would have it, a few days later Molly He, Mostafa Ronaghi and colleagues at Illumina actually published a proof-of-concept paper for just such an instrument.  Unlike many sequencing technology PoC papers, this one demonstrates feasibility of reading actual templates (phiX rides again!). 

London Calling Wrap-Up

The second, and final, day of Oxford Nanopore's London Calling conference concluded last Friday -- and I'm behind on writing it up.  Some of that was due to travel (and the wrong power supply going on the trip) and post-trip exhaustion, but failing to finish this last night was pure slacking. That route was shut down when one reader asked when I'd get things done.  Anyway, I again organized the activity into a storify story as I did for the first day of the conference. I'm going to go into less detail on individual presentations below and instead engage in the vice of far-ranging speculation.

London Calling Day 1: Highlights

Oxford Nanopore's London Calling conference kicked off today; I've Storified a large collection of Tweets from it, covering today up through about dinner.  I'll summarize some highlights below

Oxford Nanopore's London Calling: Pre-meeting speculation

Oxford Nanopore's London Calling confab starts up in a matter of hours.  Alas, several issues scotched my plans to attend (not only does it promise to be an exciting conference, but I simply love exploring London on foot).  It is worth emphasizing that the MinION devices and consumbables have been out in the wild for not quite 11 months at this time.  In that time, Oxford has dealt with a wide variety of technical and logistical headaches. While performance is still variable, many MAP participants are forging forward and the available tools for nanopore data continue to grow.  London Calling will likely bring a burst of new announcements; Oxford's Clive Brown has been giving talks recently but has promised that exciting stuff has been reserved for the confab.  Below is a set of semi-informed speculations calling out likely happenings, mostly based on Clive's recent presentations and tweets.

PacBio's New Sample Prep Plan: Too Late to the Dance?

Pacific Biosciences had a string of announcements around its earnings release last week.  Of particular interest is a collaboration with RainDance to develop a new sample preparation system for generating long synthetic reads from minuscule inputs.  If some of that sounds familiar, the loose outline in the press release suggests an approach similar to that of 10X.  But is this proposed system arriving too late to the party?

Revisiting the RNA Tie Club

As mentioned previously, by wonderful luck I now have regular contact with Ash from the Curious Wavefunction, and he has stimulated a new burst of scientific history interest in me.  I've ripped through a bunch of scientific memoirs -- by Crick, Djerassi and Dyson -- and have learned how to summon the biographies of Wilkins and Chargaff, as well as trying to dive again into The Eighth Day of Creation.  One topic I keep stumbling across is an interesting little bit of genetic history called the RNA Tie Club, which is a story worth re-telling and re-examining

Interested in the History of Biotech Companies? Don't start with Wikipedia.

I'm generally a big fan of Wikipedia and use it often for background research.  I've gotten more active this year in editing it, particularly around biographies of scientists.  For example, this year I've made major additions or edits to the entries for Walter Gilbert and Arthur Pardee and the , created entries for Martinas Ycas, Benno Müller-Hill, Monica Riley and Helen Donis-Keller. I also stumbled my way into a campaign of major revisions to the entry on Marie Antoinette, getting sometimes into a revision war with one other editor (which we resolved with a truce).  Along the way I've gotten almost adept at writing Wikipedia references and discovered a bizarre recurrent vandalism of Wally's page in which the vandal changes his name and personal details.  Recently, I've discovered a whole category of flawed entries: those on companies in the biotechnology industry.

To Properly Assess Cancer Genomics, One Cannot Dismiss It

Through a happy series of professional events, I now get to have lunch very regularly with the author of the excellent blog The Curious Wavefunction.  If you haven't visited there, Ash not only delves into chemistry but the history of science.  In a most friendly way, he dropped a challenge on my Twitter-step that represents a long procrastinated blogging project, so I really couldn't turn it down.  And that challenge is: what has been the value of cancer genomics. Is it, as he asked, a very expensive exercise in looking for keys under the lamppost, or something far more valuable?

A Dovetail Route to Scaffolded Genomes

10X Genomics had a lot of buzz at AGBT over their approach to acquiring long range information for complex genomes via a microfluidic-assisted library preparation scheme.  Another young company, Dovetail Genomics, is starting to unveil a very different technology with similar aims.

An Impending Shakeout In Library Prep?

My ABGT teleconference-based pieces all had a theme of library preparation.  Library prep has never been as flashy as instrument performance, but is clearly critical.  A library-free sequencing technology remains a distant dream, so DNA (or RNA) must go through a series of preparative steps prior to being loaded on the sequencer.  The dominant library prep molecular biology for clonal sequencing systems consists of shearing the DNA mechanically, making flush ends with a repair mix, adding 3' runs of A and then ligating primers and finally using PCR to amplify the material.  

Mechanical shearing can be replaced with enzymatic shearing (or perhaps even chemical, though I'm unaware of chemical shearing being used in production).  For RNA of different sorts,

some upstream steps are added to convert the RNA to DNA, perhaps with a depletion at some stage of hyperabundant species such as rRNA.  This conversion may, with different levels of success, mark which strand was sense and which antisense. The transposase-based Nextera protocol represents the most drastic departure from this paradigm, enzymatically eliminating all the steps prior to PCR. 

There's Gold in Them Thar Programs

Last night was the season five finale of the Gold Rush, which I confess is one of the few television programs that I have been watching routinely near their airing schedule (the other is The Simpsons, which is a father-son bonding experience). Now, writing in a blog mostly about science that you watch something on the Discovery Channel is a bit of a bold act, given its many panderings.  The network annually features Shark Week, that has been roundly criticized for its sensationalized portrayal of these magnificent creatures.  It also features shows which purport to show individuals routinely engaged in felonies and in one case claiming to document a violent subculture in a pacifist religious community, the Amish.  I grew up near the Amish Country of Pennsylvania; if anything like that ever existed the Philadelphia papers would have had a field day.  Gold Rush itself, and a second gold show which I've developed a fondness for, Bering Sea Gold, has shortcomings that are obvious and painful.  So why am I hooked?

Can BGI Really Stir Up the Sequencing Instrument Market?

I've been asked several times recently about rumors coming out from BGI.  They've started claiming they have a super sequencer which will radically beat Illumina's offerings on both cost and accuracy. The recent 10K Genomes meeting apparently had a quick talk from BGI which led to some limited Twittering, and judging from this Mendel's Pod interview at least one person believes the buzz (though the same individual quotes a price per PacBio human genome that high by at least a factor of 25). .  The claim is that this summer at ESHG BGI will release two boxes, one a benchtop model which I haven't seen any details on, and the other claimed to offer throughput superior to a HiSeq with better accuracy.  What might be backing up these claims?

What's Been Cooking for Ion At AGBT15

Rounding out my remote coverage of platform news from AGBT, the Ion Torrent team also lent me some of their time (and at risk of sounding obsequious, I do greatly appreciate this -- vendors have almost no down time at these events) to touch on some of the topics I I wrote about in my Ion history and speculation piece.

10X Reveals Its Facets

Perhaps the heavily anticipated launch at AGBT this year is the library prep instrument for 10X Genomics.  This Bay Area startup made a huge splash at the beginning of the year by announcing a monster ($55.5M) financing.  A member of my professional network had been part of the early team and had given me very minimal hints at last year's AGBT, so I've been eagerly awaiting details for a long time. Several members of 10X's team were kind enough to chat with me by phone yesterday with the proviso that I hold off on launching this piece after their talk today at the conference (interestingly, I had crossed paths with all of them in some previous setting).  Also, they sent me some promotional materials and permitted me to post some clips from them. Now, the GemCode system is officially launched, with orders being taken now and devices planned to be delivered in early Q2.

Illumina Launches NeoPrep (#agbt15)

The 2015 AGBT conference started out today.  A few hardware makers have let me chat by phone with members of their team, since they're there and I'm not.  Tonight's dispatch is from a chat with Illumina focused on their now launched NeoPrep library preparation instrument

Can Ion Torrent Buzz Again?

In my AGBT 2015 Preview / Speculation at one point had a tightly packed (and overly long) paragraph on Ion Torrent, but I realized that this was a symptom of trying to to cram too much in too little a space -- plus I really had a lot more thoughts worth unpacking.  So here's a long form look at Ion Torrent -- with plenty of references to past AGBTs to make writing this now apropos.  One advance bit of excuse making: the historical background that follows is not intended to be a comprehensive history of Ion Torrent technology, but more of an impressionistic sketch (but as always, my worst excesses and omissions are fair game for comments!).

#AGBT2015 Preview

The annual genomics party on Gulf of Mexico beaches named AGBT runs next week, and already there have been some speculations flying.  I'd better dash something off before I'm any later to the preshow -- or more importantly before I get contaminated with embargoed information.

The MBTA Must Embrace Data!

As you may have heard, we’ve had a bit of snow in the Boston area recently.  Two storms, one the beginning of last week and one which just ended yesterday, each dumped close to a meter of snow in the area.  The two storms each had different profiles: last week’s storm featured rapid snowfall and furious winds, with the snow falling over a 24-36 hour period.  The more recent storm started on Friday afternoon, ended on Tuesday morning, with a steady fall of lazy snowflakes.  Last week a hare, this week a tortoise.  But both weeks, a paralyzed Boston from a transportation standpoint, with the MBTA mass transit system performing dismally.

Unfortunately, the main response to that failure has been a lot of political theater. GM Beverly Scott gave a press conference yesterdaythat featured the usual refrain: the system features antiquated equipment, our crews are working hard, nobody could deal with this.  In other words, a string of unquantifiable and unactionable clichés.  There's already an unhelpful murmur in the press that Scott might be fired, which would seem little fix but mostly fodder for more column inches of newspaper opinion (such as this and this)