Monday, October 31, 2016

Tidying Loose Nanopore Patent Threads

A commenter on my recent piece on Genia made a number of assertions with regard to nanopore patents.  A more general one was a complaint that I had covered the opening salvo of the battle from Illumina and University of Washington  and Oxford's formal response and feinting to the CsgG/R9 pore, but failed to cover the campaign's termination.  It's a fair charge and I'll rectify this here.  My (rather lame) excuse is the news broke while I was on vacation in the Pacific Northwest and trying to avoid any remotely professional activities, other than reading Luke Timmerman's Lee Hood biography.  But, that doesn't excuse not writing something on my return.  If you're going to enjoy flame-broiled steak, one must clear the vegetables from one's plate.

Friday, October 28, 2016

10 Years of Omicing!

Today marks a special day - it was 10 years ago that I launched this endeavor.  I'm going to take time today, and perhaps a few times in the near future, to look back on the journey.  Ten years of blogging also happens to be around my anniversary of starting work at Millennium, which means I've been a professional in biotechnology for two decades.  So I must be old; indeed, this summer I celebrated birthday 30 (numeric pedants might make the base charge that I am misleading by not writing that 0x30) and about a quarter century since I launched into bioinformatics full time.  So a bit of nostalgia seems not out of place.

Thursday, October 27, 2016

Segmental Duplications and Deletions in Books of History and Life

I have long had a historical interest in the U.S. Civil War.  In fifth grade we had an all-day field trip to the Gettysburg Battlefield, which is very well preserved, and it enthralled me.  A few years later I would hike all over the battlefield with my Boy Scout troop, which is probably even closer to experiencing a taste of what it was like to be soldier. Of course, we had good hiking boots - a proximate cause of the battle occurring there was an attempt by the Confederates to raid a shipment of shoes which had just arrived in the town.  My great-grandfather served in the Union Army, though entirely on garrison duty.  However, his two older brothers saw action and one lost an arm at Chickamauga.  I just failed for arguably the fourth time to get to that site, but I've toured a few other key fields (Antietam and Petersburg).

Wednesday, October 26, 2016

How Genomes Enabled Proteomics

My recent piece on the folly of moonshot projects caught the eye of a Silicon Valley blogger named Kumar Thangudu (@datarade), who gave me some nice praise. But along with that were some notes of his on other big science projects, and one he targeted was the Human Genome Project, with a sarcastic comment about the paucity of drugs coming from the HGP.  Them's fighting words!  So I launched a tweet stream his way outlining a number of impacts of HGP on biomedical science, and he was very nice and suggested I write more on that. I'm thinking of a number of angles on the topic, but here goes a bit of nostalgia that I think illustrates a number of points on the topic.  Except I'm first going to talk about Escherichia coli, and worse, talk about it before its genome was complete.  But that's part of the point.

Tuesday, October 25, 2016

Messaging Counts

My recent piece on SeqLL's reboot of the Helicos sequencing technology attracted a number of helpful comments either on blogger or via email.  Several of which pointed out the high suitability of this box for counting applications such as expression profiling, ChIP-seq and copy number analysis. Julia Karow of GenomeWeb graciously provided me with a copy of her piece, which underscored the value of GW in having real reporters dig into a subject.  Much of what she dug up concerns SeqLL's future plans and for the near term mostly confirms suspicions that the technology will mostly look like the previous Helicos box, just scaled down.  But Julia also got out of SeqLL some of the numbers that are shockingly absent from the press release, such as the throughput (though I don't see the number of channels, a key aspect of this technology as covered below). My correspondents also pointed out a number of careless errors in the piece: I sliced $100K off the price of the PacBio Sequel (doesn't mean you can't try to get them to honor it!) and the In Sequence brand is long-gone from GenomeWeb's site.

Sunday, October 23, 2016

SeqLL: Helicos van Winkle

Helicos was the first company to launch a single molecule DNA sequencing system. They never sold many systems (my estimate is fewer than 20), but some of those sites really loved their machines. One beauty of the system was a very simple sample prep: fragment your DNA, add terminal transferase and dATP and the sample was ready-to-hybridize.  Helicos demonstrated a number of interesting applications, such as direct loading of RNA onto the system and performing capture on the flowcell.  But with anemic demand and mounting losses, the company faded, finally filing for bankruptcy in November 2012.  One true believer bought up key IP and hardware and kept the torch burning as SeqLL, headquartered just down the road from me in Woburn, Massachusetts (best known for the book and movie A Civil Action, but also the birthplace of thermodynamicist Count Rumford ).  Now SeqLL is re-launching the technology in a new box, or is it similar technology? That's the big question, poorly addressed by their beta test announcement or their website, and that website seems to be positioning the new SeqLL box against the state of competing sequencing technologies of back when Helicos folded.

Friday, October 21, 2016

IGenomX Launches New Linked Read Chemistry

A hot concept in the genome world is how to capture long-range information, enabling assembly through repeats, resolving haplotypes, resolving copy number variation and many other applications in which short reads from short fragments are just not sufficient. A number of approaches have been proposed and published over the years, with some hitting commercial markets and significant use.

Wednesday, October 19, 2016

Genia Publishes Polymerase-to-pore docking scheme

Back in April, I wrote up a PNAS publication from Genia and collaborators that described the modified nucleotides they have developed for their sequencing-by-synthesis with nanopore detection sequencing scheme.  I had the opportunity to chat with George Church (who is an adviser both to my company and Genia, and a co-author on the paper) just after that and he remarked that there was a companion paper in the works describing the polymerase engineering for the system.  That paper is now out in PNAS (and Open Access) and I'll take a little walk through it.

Monday, October 17, 2016

Sequencing, not random probes, are future of microbiological diagnostics

Okay, I'll admit I take requests.  Throw a topic at me by Twitter or email, and if it piques my interest and I feel like I can say something intelligent, then I'll take it on -- but not necessarily instantly.   That's the genesis of today's item, a tweet from Kyle Serikawa directed at me, asking if a new paper  from groups at Rice and Baylor College of Medicine in Science Advances on a proposed microbial diagnostics (a paper highlighted by Eric Topol) had any legs.

I'll fully confess that I realized upfront that this paper cuts across my usual biases, so I resolved to try to read it with that in mind.  That's not really an excuse in the delay; I did read the paper right away, but the usual conflicts stretched out writing it up.  The paper, in brief, proposes a non-sequencing approach to an area which I had previously thought was going to be totally dominated by sequencing, and I inherently like sequencing.  After reading the paper, I would agree with Kyle: I'm not convinced that this method has legs.  It doesn't help that the paper has some serious issues with describing the methodology, as well as utterly failing to make its computational methods available.

Thursday, October 13, 2016

DNA: How Clean is Clean Enough?

Nick Loman has a new blog post nicely covering the current state of affairs for DNA preparation in the field.  Earlier this year I had some thoughts about DNA preparation and the degree to which our current methods reflect history rather than some ideal.  Even before Nick's post I had some new thoughts on the topic, but seeing his exposition helped me consolidate my own musings.

Thursday, October 06, 2016

Bill Gates Succumbs to Moonshot Madness

Another day, another misguided call for a moonshot in human disease.  This time, it's Bill Gates laying out four goals that he believes can be attained in the next decade, given the correct amount of dedication and determination.  Among these goals are a vaccine for HIV and a cure for neurodegenerative diseases.  I'll focus my comments on the neurodegenerative diseases with a few comments about fellow Blue Hen Joe Biden's cancer moonshot, but many of the criticisms apply to the HIV or just about any serious disease.

Wednesday, October 05, 2016

ONT's Wafer Thin Update

Oxford Nanopore's Clive Brown gave an hour-long update on their platform last week.  A busy social schedule featuring (on different nights) GMO beer and challah - plus six hours travel each way to the challah-fest. Add atop that a fast-moving upper respiratory tract infection, and I'm even more behind in blogging than usual for such events (plus I gathered another post idea away -- and had another suggested to me). Time to get working on the backlog!