Peering Through the Flowcell Glass, Darkly

As 2013 draws to a close, I've decided to stick my neck out and make some predictions for 2014.  Perhaps I'll get lucky and a few will even come true!  After several mental experimentations on the structure, I'll settle for stepping roughly past each major player.

Assembly Could Benefit From More Circular Reasoning

It was very gratifying to get comments on my recent piece on a de novo assembly review from both a referee of the manuscript (the amazing Heng Li) as well as one of the authors of the piece (though I am truly feeling guilty I forgot to reach out to the authors).  Of course I was having my usual post-post regrets of things not written, such as the whole interesting topic of dealing with (and leveraging) uneven coverage in metagenomes and when assembling from amplified samples.  But one other thing I was reminded of is one of the minor complaints I have with assembly programs: a lack of proper handing of circular genomes.

Assembling a Review of a Review of Assembling

A review on short-read de novo genome assembly appeared recently in PLoS Computational Biology, titled "Next-Generation Sequence Assembly: Four Stages of Data Processing and Computational Challenges".  I think the review has a number of merits, but I also find a number of frustrating flaws.  I'm going to write this entry much as I would have written a referee report on it.  Unfortunately, that will mean I'll dwell a bit more on the flaws than the assets, but if you are interested in the field

Did The Biochemists of Yore Know Morse Code?

So, this piece is going to be mostly asking questions.  In one of the corners of my dream world I have a scientific historian on retainer, but in the real world my substitute is to throw some questions out and hope some knowledgeable people leave comments.  If someone I spark someone’s term paper or thesis topic, I ask only that I get an electronic draft!

Spanish Prisoner, ZX-81 or Turbo Pascal?

In  the movie The Spanish Prisoner, a brilliant inventor possesses a paranoia that "The Process" he has invented will be stolen by deceitful competitors, and everyone speaks with a highly distinctive cadence. The entire movie is suffused with deceit, starting with the title which is a notorious con scheme akin to the modern Nigerian scam. I spent last evening in some of the space in which the movie was filmed listening to a scientist in that mold (& distinctive speech) describe a process his group has invented (indeed, by lucky chance I helped him find the venue). But many remain unconvinced that Clive Brown and Oxford Nanopore are not themselves the puller of ocular wool.

Ion Previews More Accurate Polymerase, Faster Template Prep

I haven't talked about Ion Torrent for a while, because it was largely off my radar screen.  In early 2012 the PGM had been an important contributor to my early de novo genome assemblies, as it was the only fast turnaround, low cost system I could access.  But the data quality was always frustrating, with many indels, and the 200 basepair mode on the read lengths not great for assembly.  Once I could access a MiSeq, that became our dominant instrument for individual genome assembly.  We tried Ion once more with the 300 basepair chemistry, but were not particularly impressed.

Ripples from 454's Shutdown Announcment

Roche's announcement this week that they planned to shut down the 454 sequencing business in mid-2016 was not completely unexpected, as a number of rumors of shutdown had shown up on Twitter.  Most tweets on the subject fell into two categories: either just-the-facts-ma'am or jokes about the dominant error profile (which I guess you could call just the facts maaa'aaam).  But, certainly I wouldn't have thought Roche on the verge of this decision when I went to AGBT 2013 in February, as 454 had a huge suite in a prime location (just by the main conference hall entrance) and many expensive events. Now, Roche's presence in the genomics space is looking like just the recently announced deal with PacBio to market human diagnostics on that platform.

Roche Taps PacBio for Human Diagnostics

One of the two big buzzes in the genomics business world was the announcement that Roche Diagnostics has signed a major deal with Pacific Biosciences in the field of human diagnostics, which comes with a $35M upfront payment and a possible $45M in milestones, plus future sales of reagents.  PacBio stock rocketed over 70% on this news. This on the same day that cancer diagnostics company Foundation Medicine went public with a similar potent climb from their offering price; a good day for those lucky enough to have the shares (which, by the way, does not include me in any way, though Foundation shares a common venture backer with Warp Drive Bio in Third Rock Ventures).

Potential Sources of Drag on PacBio's Long Read Performance Trajectory

Over at Homolog.us there are two detailed blog entries on Pacific Biosciences entitled "End of Short Read Era?" (Part I  and Part II).  I've tweeted a number of comments on the technical aspects, but there are some more substantial thoughts reading these pieces helped me condense.

SGE Isn't For Dummies (I sort of wish it were)

Kendall Square used to have the ultimate geek book store, Quantum Books.  No fiction or graphic novels there; it was all technical books.  One could browse every O'Reilly book and many, many others.

My biggest contribution to the field of biochemistry

LinkedIn has a feature by which one can endorse other people for different fields. Periodically the system prompts me to vote yea-or-nay on a bunch of endorsements, and conversely I get regular updates as to what others have endorsed me.  It's always nice to get a vote of confidence, but sometimes I find myself wondering what it really means.

An Incomplete Guide to Asking for Help on Your De Novo Genome Project

I've been thinking about this piece for a while, because I am a frequent presence on SEQAnswers.com and often dive into questions regarding de novo sequence assembly, particularly for small genomes.  It's good to help out and a way to feel like one is contributing to a broader community, but sometimes it can be very frustrating because the seekers (SEQers?) of help do not post their questions very well.  So, it would be helpful to have a post to point them to, though I'm sure there are considerations I either haven't thought of or will fail to remember to add.  So, those can either go into the comments or a future post, or perhaps something can go in the Wiki at SEQAnswers.

But in general, think of it this way: you have some experienced hands in a field you wish to enter, who are willing to give detailed advice for free.  But, they can't give that advice unless you specify your question well, and if you don't get it right the first time they may not see (or may ignore) your second shot.

What Might Knock Illumina Off Its Perch?

The big sequencing platform news this week is Roche's announcement that they are ending their collaborations aimed at developing new sequencing technologies.  A collaboration with DNA Electronics aimed to create an Ion Torrent-like system whereas a more ambitious effort with IBM aimed to create instruments based on "DNA transistors".  As noted by Forbes' Matthew Herper in a thought-provoking piece, Illumina is sitting very high atop the sequencer market.

For What is a 454 Still Great?

I've been mulling this item ever since AGBT, but have struggled with the title.  I don't want to sound like I have a grudge against 454 ( truth is I just got some good datasets off this technology), but I do believe that they are few papers away from being stampeded.  Or perhaps not; perhaps the community is really wedded to this platform.

PacBio Back of the Envelope Numbers

Back-of-the-envelope calculations can be quite useful, but also quite dangerous.  They are meant to be quick estimates, but can't be taken too seriously.  Still, I try to get them right & deeply regret overestimating recently on Twitter the cost of a human genome on PacBio by 3X.  Twitter is particularly dangerous: tempting to fire off a note, but impossible to pack in the full calculation

Post AGBT: A Longish Item on Long Sequencing

As others have noted, a significant theme at AGBT this year was sequencing at length.  While this year lacked true bombshells, PacBio impressed many with their making single-contig bacterial genome assemblies look easy.  Moleculo had been the object of much pre-meeting excitement, and while very few additional details emerged about their process, several talks showed what could be done.  As I have discussed previously, Nabsys demonstrated their “positional sequencing” system to select invitees in a hotel suite.  Optical mapping from OpGen and BioNano Genomics featured in a few posters, but did not attract much attention.  Oxford Nanopore had no physical presence, beyond a somewhat secretive suite, but several ONT staffers were happy to reiterate their confidence that they will launch their system – when it is good and ready.

AGBT: Nabsys unveiled

In the previous post I described the Nabsys positional sequencer. Yesterday I got o see it running in their hotel suite here at AGBT13.

AGBT Preview: Nabsys

A complaint which seems to be circulating on Twitter and elsewhere is that this year’s AGBT conference on Marco Island next week doesn’t look like it will have any excitement around new platforms.  AGBT has been a traditional coming out party for platforms.  Last year it was Oxford Nanopore which created a huge buzz, and in previous years that crown has been held by Ion Torrent, Pacific Biosciences, Complete Genomics and others (including a few which seem to have gone kaput).

It is hard to argue that this year’s program is much more heavily tilted towards applications of genomics than novel genomic technologies.  Many of the genomic technology talks are updates on the evolution of existing platforms such as PacBio and Illumina (especially the Moleculo technology).  But, there will also be novel technologies.  

This past fall I had the pleasure of spending half a day with the folks at Nabsys, located a short distance from Boston in Providence RI.  Nabsys’s buildings are in a sea of drab parking lots (not to mention sheriff’s cars; a courthouse is nearby), but on the interior were quite pleasant.  I was largely wearing my “day job” hat that day, but Nabsys will be unveiling their instrument at AGBT and has given me permission to talk about what I saw (and reviewed what I've written to make sure I didn't make some dumb errors, though the content is all mine).  Of course, I will update this after I look some more at AGBT.

Matthew Yuricich: A Pre-Oscar Tribute

I'm committing myself this week to an uncommon intensity of posting.  It's AGBT week, and while I'm there I plan to be busy both here and on Twitter.  Genomics has always been the focus of this space, but once in a while I beg the readers' indulgence while I write on something else.  Just after AGBT comes the Oscars, and in the likely case I'm completely exhausted (though sitting much more comfortably than I was for last year's Oscars), I want to scribble a long-overdue tribute.  For when the montage appears of previous winners who died since the last telecast, I'll be looking for the only Oscar awardee I ever met.  The nature of his work meant that many are utterly unaware of it, but he contributed significantly to the visual spectacle of many films, including one which influenced the look of a vast number of films of the same genre that followed it.  

Moving day

I was originally going to start this with a joke alluding to one of the signature special effects of Star Trek: The Next Generation, but given the recent events in Russia it's probably in poor taste to speak lightly of flashes in the sky.  But, after much preparation, today was the day that Warp Drive Bio completed packing up, with next week ushering in our new facility.

A Short(ened) Note on Ion Torrent & High G+C

As one might guess from reading this space, I always have an itch to try new sequencing technologies or updates to existing ones.  That's generally a good thing in my position, though more than a few times I experience buyers remorse.  At least this time, I found something a bit interesting

Illumina's Blizzard

As the clear leader in the genome sequencing technology market, Illumina is often in the news.  As befitting the winter season, there's just been a blizzard of Illumina news, mostly announcements from within but also two important external ones (an excellent summary of these can be found at NextGenSeek).