Farewell Nabsys

A bit over a week ago brought news that mapping instrument hopeful Nabsys had ceased operations.  As a veteran of one failed biotech, I have a lot of sympathy for the team there. Plus, I knew a bunch of folks at the Providence RI firm.  Nabsys's signle molecule mapping technology was a wonder -- what single molecule technology isn't? Already stories are emerging of a disgruntled founder who wants to buy up the intellectual property and give it another go. It is easy to admire that stick-to-it spirit; it's a lot harder to find a rational reason to believe that such a revival will be any more successful.

How Do You Differentiate Archea and Bacteria in the First Week of High School Biology???

I have a long standing interest in biology education -- I seriously considered it as at least a career to explore -- but now I really have skin in the game.  TNG just executed a schedule move that will defer his biology this year to the second half of the term, but I also have a niece who is taking AP Biology at her STEM high school.  Even in his short time in biology class, TNG has succeeded in asking for homework help that has me scratching my head.

Freely & Unrepentantly Confessing to Heresy

Keith Bradnam reported a huge influx of traffic for a recent post -- not surprising, since he labeled it NSFW (Not Safe For WorK).  And yes, despite my skepticism that it would be truly offensive, I'll confess I checked it with phone, not my work laptop.

Ion's S5

The Ion Torrent team rolled out a new sequencer line this morning, the S5.  The S5, whose impending release had been tipped on the internet by the leak of a manual, arrives in two models, the standard and the XL, which differ only by on-board computing power and not sequencing metrics.   As has been the trend, Ion's focus is entirely on focused sequencing, and the new lineup emphasizes making targeted sequencing with AmpliSeq and other approaches fast and simple.

The Road to Hell is Paved with Bioinformatics Formats

If you really want to raise a bioinformaticist's blood pressure, loudly declare your new tool generates output in brand new data formats.  This leads to the frequent observation that a large fraction of bioinformatics work is simply converting formats. It is probably consensus that the field is awash in too many formats, though it is equally clear that we can't agree on which should survive.  Between some recent news and a Twitter thread on the subject that erupted last night, there was a bunch of fodder for me to collect in a Storify -- and to lay out my own idiosyncratic views.

Do Helix's Numbers Work?

A number of efforts in the consumer genomics space have been attempted in the past, with 23andMe appearing to make limited headway and Knome not much at all.  I haven't been able to get any investment interest in my own concept, though perhaps that's because it was tongue-in-cheek (or tongue held out while panting).  Last week brought a big splash, with a new company Helix launching with $100M and three major players as backers: Illumina, LabCorp and the Mayo Clinic

Clinical Metagenomics Pipelines: Revisiting & Reflecting

When I set out to start this blog nearly over eight years ago, I set myself a number of goals.  One goal was to take some risks -- not crazy risks but to not just play it safe.  But counterbalancing that goal was one to be open, accurate and honest. My piece last week on clinical metagenomics pipelines had a fair amount of attention, and resulted in an ongoing electronic conversation with one of the key parties.  In the course of this, there are now parts of that piece I wish I had handled differently. Some other important topics have been raised, and I would like to cover here.

Leaky clinical metagenomics pipelines are a very serious issue

Update: Some significant issues with the tone of this post are discussed in a follow-up.

I am a firm believer that the practice of science is the result of contingency; we do not necessarily have the best scientific culture possible but rather one which has evolved over time driven by chance, necessity and human nature.  We should never hesitate to re-examine the way science is actually practiced, and that particularly holds true for how we analyze data and publish results.  A re-analysis of a prominent Lancet paper has just come out in F1000, and this work by Steven Salzberg and colleagues illustrates a number of significant issues that slipped past the conventional peer review publishing practice

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.