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)

How not to write a sequence assembly comparison paper

Lex Nederbragt flagged, via Twitter, a preprint on the F1000 site with a questionable table comparing sequencing systems.  Alas, once I looked at the paper I've gotten myself in a state where only writing up its numerous deficiencies will free my mind of it.  I've even volunteered to F1000 to review the paper, but I haven't heard anything and so I will use this space.  I'm afraid this paper fall into the small category of manuscripts that I would recommend rejection.

The preprint is titled "Advantages of distributed and parallel algorithms that leverage Cloud Computing platforms for large-scale genome assembly".  Alas, the paper doesn't attempt to deliver anything of the scope promised by that, and the abstract isn't much better.  Most papers have a certain amount of preamble and then deliver some new finding; the preamble to the paper is overlong and badly executed, and the work in the paper is far too minimal and also badly executed.

Cargo Cult Networking & Other LinkedIn Laments

LinkedIn is a social media tool I find greatly flawed, but useful.  Part of the devil's pact one makes with LinkedIn is to receive great amounts of requests from individuals who wish to grow their networks.  I have a personal guideline for such which help me weed through the requests, but last year I got a request that had me laughing -- and slightly revising that guideline.

JPM Wrap-Up:

In this final installment of a series of reactions to news coming from the J.P. Morgan Conference, I'll cover an interesting complementary technology that was announced.  But first, it might appear my prediction of no radical sequencer announcements may have been invalidated, with an announcement from BGI of plans to launch two sequencers based on Complete Genomic's technology.  Unfortunately, the only outlet that seems to have covered this is GenomeWeb, and it is in their premium (paywalled) section, so I know nothing beyond that.  It appears this was only announced around JPM and not at JPM, so I have a Clintonesque out as well.

Illumina's Expanded Lineup

In my JP Morgan predictions for sequencing platforms, I didn't do badly.  The only major player to make a platform announcement was Illumina, and they did indeed announce instruments that are not radical departures from the prior platforms.  I am kicking myself for not making more specific predictions, as the nature of the new boxes was really unsurprising and it would have been nice to nail that.

2015: Another Year of Sequencing Evolution (not Revolution)?

The J.P. Morgan Conference is firing up, and for the past few years that has meant big sequencing platform announcements -- HiSeq or Ion Proton or such.  This has stolen some of the thunder from AGBT in terms of major announcements (sadly, I won't be attending this year -- and will try not to land my self into surgery the way I did the last time I didn't attend AGBT).  I figured I'd better write this tonight before any more JPM-related sequencing instrument announcements show up, or more to my prediction, before the conference ends without any.

Druggability: An Underappreciated Issue in Translating the Human Genome Into Therapeutics

I'm sorely guilty of neglecting this space, but a recent (and now storified) Twitter conversation from Jonathan Eisen (@phylogenomics) has improbably fired me up enough to scribble something.

Reanalysis Lays Bare MinION Review's Spectacular Flaws

I will confess that when our first MinION burn-in data for lambda came in & I threw a few aligners at it (after first getting my data extractor in Julia shaken out), I was disappointed at the results.  Very few 2D reads, very few aligned reads and the alignments all short.  At this point, I sat back to wait to see what others had experienced and to think of additional bioinformatics approaches.  It never occurred to me to dash off a glorified  blog post and submit it to a journal.

Oxford Takes Some Flak, Fires Back

A huge event in the genomics community this summer has been the Oxford Nanopore MinION Access Program (MAP), which has enabled a sizable but select group of researchers to try out ONT's novel nanopore-based sequencing technology.  While results and rumors have periodically drifted out over the summer, this week saw three disclosures, one of which resulted in fireworks and action

The good, bad & missing from Bio* libraries?

As I mentioned recently, I've been exploring how I might use the emerging Julia language to solve problems.  While that requires a large amount of mental work, I see some potential gains, both in having more readable code than Perl as well as to potentially leverage a lot of high-level concepts for parallel execution that are built into the language.  But beyond the challenge of elderly canine pedagogy that I present, there is the issue that the BioJulia library is quite embryonic, with serious consideration of treating much of the existing code base as a first draft (or, that is the impression I get from skimming the Google group).  So I'm going to try to pitch in, despite my multiple handicaps.

After the New Yorker piece, what of disruptive innovation?

I don't read a lot of books aimed at the MBA crowd, but one set I have liked, and sometimes cite here, are Clayton Christensen's on inovation and disruption.  As you may have heard, a recent article in the New Yorker by Jill Lepore took a gimlet-eye view to the whole concept and raised serious questions about Christensen's methods.  This was then summarized by another author in Slate and since then Christensen has responded in part via a Business Week interview.  He's also scheduled to be interviewed on PBS this weekend, so likely there will be further developments.  Indeed, after sketching this out on the commute home I discovered a Financial Times article whose tone is very similar to what I have written below.

Dabbling with Julia

As I've remarked before, I've done significant coding in a large number of languages over the last 35-or-so years.  I don't consider myself a computer language savant; I've known folks who can pick up new languages quickly and switch between them facilely, but for me it is more difficult.  I haven't tried learning a new language in perhaps 5 years, but this week I backed into one

NGS Saves A Young Life

One of the most electrifying talks at AGBT this year was given by Joe DeRisi of UCSF, who gave a brief intro on the difficulty of diagnosing the root cause of encephalitis (as it can be autoimmune, viral, protozoal, bacterial and probably a few other causes) and then ran down a gripping case history which seemed straight out of House.

A Sunset for Draft Genomes?

The sun set during AGBT 2014 for a final time over a week ago.  The posters have long been down, and perhaps the liver enzyme levels of the attendees are now down to normal as well.  This year’s conference underscored a possibility that was suggested last year: that the era of the poorly connected, low quality draft genome is headed for the sunset as well

How will you deal with GRCh38?

I was foolishly attempting to catch up with Twitter last night during Valerie Schneider's AGBT talk last night on the new human reference, GRCh38. After all, my personal answer to my title is nothing, because this isn't a field I work in.  But Dr. Schneider is a very good speaker and I could not help but have my attention pulled in.  While clearly not the final word on a human reference, this new edition fixes many gaps, expands the coverage of highly polymorphic regions, and even models the difficult to assemble centromeres.  Better assembly, combined with emerging tools to better handle those complex regions via graph representations, means better mapping send better variant calls.

So, a significant advance, but a bit unpleasant one if you are in the space.  You now have several ugly options before you with regard to your prior data mapped to an earlier reference.

The do nothing option must appeal to some. Forgo the advantages of the new reference and just stick to the old. Perhaps start new projects on the new one, leading to a cacophony of internal tools dealing with different versions, with an ongoing risk of mismatched results. Also, cross your fingers that none of changes might be revised if analyzed against the new reference.  Perhaps this route will be rationalized as healthy procrastination until a well-vetted set of graph-aware mappers exist, but once you start putting-off it is hard to stop doing so. 

The other pole would be to embrace the new reference whole-heartedly and realign all the old data against the new reference. After burning a lot of compute cycles and storage space running in place, spend a lot of time reconciling old and new results. Then decide whether to ditch all your old alignments, or suffer an even larger storage burden.

A tempting shortcut would be to just remap alignments and variants by the known relationships between the two references. After all, the vast majority of the results will simply shift coordinates a bit, but with no other effects.  In theory, one could estimate all the map regions that are now suspect and simply realign the reads which map to those regions, plus attempt to place reads that previously failed to map. Again reconciliation of results, but on a much reduced scale.

None would seem particularly appealing options. Perhaps that latter route will be a growth industry of new tools acting on BAM, CRAM or VCF which themselves will provide a morass of competing claims of accuracy, efficiency and speed. Doesn't make me at all in a hurry to leave a cozy world of haploid genomes that are often finished by a simple pipeline!