Biotech Marketer

Neil Hall is Responsible for Rising NGS Prices

2013-05-16T11:14:00.000-07:00

“Wait, what?! Neil Hall is responsible for NGS prices actually inching up rather than continuing down to ever lower depths?”

No, not really.

Well, he kind of is. And most likely so is everyone reading this blog. (All three of you.)

It’s because DNA sequencing consumers didn’t ramp up their usage as quickly as Illumina was driving down the prices. When Illumina bumped HiSeq capacity from 300Gb per run to 600Gb per run, their customers said:

“Yay! The same amount of sequencing for half the price.”

To which Illumina responded:

“What? No, no, no, no! You’re supposed to sequence twice as much. Actually, you’re supposed to sequence even more because the cost is so low that new applications are now feasible”.

And the stock market said:

“Hmm, I’ll have half that market cap back, thank you.”

So Illumina learned their lesson and decided to be more careful about releasing upgrades for the HiSeq. Right around the time they launched the 600Gb system, they said they were able to generate runs of over 1Tb in house. It’s been around two years since then, but still no update.

Why not? Because there isn’t any market pressure to do so. The only competition HiSeq had was SOLiD, but that platform has essentially been abandoned by Life Technologies as a commercial failure. (You can love SOLiD reads all you like, but even with a much bigger marketing and sales budget, it was still getting trounced by HiSeq. Too bad they didn’t release Wildfire a couple of years earlier – we might not be having this conversation right now.)

And while Illumina was busy dominating the high throughput NGS market, Ion Torrent came out and tried to carve out a different niche: much faster, much cheaper machines (albeit with lower throughput). And that niche has really taken off (especially in the clinical space). Illumina responded with their own machine (the MiSeq) and since this is the only space where they’re facing serious competition, it’s where they are concentrating most of their resources. This means we’re now getting much faster reads, but they aren’t really getting any cheaper.

So is the party over for cheaper reads? Since the ‘plateau’ was caused by market forces and not technological advancements, the answer is almost certainly “no”. Researchers will figure out ways to creatively use ever more sequencing capacity, and when they start bumping into the limits of what the current machines can do, those machines will almost certainly improve. And the competition could come back. Ion Torrent has stumbled on their original road map, but if they ever release the PIII chip, that could put pressure on the HiSeq. And while Oxford Nanopore is the latest to suffer from the hype-hate cycle, there are a lot more companies waiting in the wings to dethrone Illumina. Check out BlueSEQ’s ‘Emerging Technologies’ section of the NGS Knowledge Bank for a partial list.

Dr. Hall is right that the field would benefit from genome scientists focusing on “new ideas”. He’s also right that the cost of sequencing will plateau. But I don’t think we’re quite there yet. And where it plateaus, whether that’s $1000, $100 or $10, will make a big difference.

Edit: Gah! I totally forgot to include a link to Mick Watson's excellent take on the cost of sequencing.

X-Gen 2013

2013-04-18T11:21:00.000-07:00

I recently had the pleasure of attending X-Gen (more formally known as ‘X-Gen Congress & Expo). This meeting falls on the small side of the spectrum, with a couple hundred attendees, and that suits me just fine. I prefer smaller meetings as I find it easier to network and generally keep track of what’s going on. It does, however, have parallel tracks – RNA Sequencing, DNA Sequencing and Data Analysis – so hard choices sometimes had to be made (e.g., a talk on Illumina’s Moleculo technology or one on duplex sequencing for rare mutation detection; Moleculo won out, but I really wanted to be at both). I’m not quick enough for live blogging – I can type up notes/thoughts, or I can listen, but I can’t do both. Therefore, I’ll just mention some of the things that stuck out in my mind.

From Peter Park’s talk on the role of retrotransposition in cancer – 45% of the human genome is derived from transposable elements (most of which are under epigenetic suppression). This isn’t a new discovery, but I still find it fascinating. Same way I find it fascinating every time I hear about how our bodies harbor ~100 trillion microbial cells (dwarfing our ‘own’ 10 trillion cells). Anyway, this analysis is fairly tricky (presumably due to the difficulty of sequencing/aligning repeats), but longer reads on the horizon, like that of the Moleculo technology, should help.
John Stam discussed the role of gene regulation in common disease. He mentioned something that, while it intuitively makes sense, I still found really interesting. When he piled up the results from 50 separate transcription factor ChIP-Seq experiments, it matched the results from his DNaseI hypersensitive site ChIP-Seq almost perfectly. Genomic regions available for TF binding would need to be accessible and, therefore, hypersensitive to DNaseI, but it’s still kind of cool to see the results overlap so well. The other interesting thing he showed was that when he had very deep sequencing in a TF ChIP-Seq experiment, the resolution of the binding sites became so good that it matched with the predicted sites of the TF crystal structure. Seeing two completely orthogonal approaches match so closely is pretty amazing.
David Smith talked about studying head and neck cancers, first with RNA-Seq and more recently looking at very large genes and chromosome breaks. For example, the FHIT gene at 1.5 million bases is so large that transcription takes so long that it can interfere with replication (hence the breaks). While it isn’t directly related to the science he was discussing, Dr. Smith revealed an interesting marketing tactic (one of the worse kept secrets in the business) about Life Technologies: “SOLiD gave us $300k worth of free sequencing… back in the days with sequencing companies were willing to seduce you.” Very important to keep in mind when companies throw around market share numbers.
Cynthia Burrows is using an alpha hemolysin-based nanopore system from Electronic BioSciences (EB) to look at DNA damage and other modifications. EB is one of the nanopore companies flying under the radar. They use a small aperture capillary with a single nanopore and a dual electronic system so that translocation and measurements can be kept separate. Check out the EB entry in BlueSEQ’s ‘Emerging Technologies’ section. Her fun fact for the day is that there are ~10k spontaneous depurinations per genome in a cell per day. That definitely makes me feel like I’m falling apart!
Aleksei Akimentiev gave a really interesting talk on solid state nanopores. While he didn’t have any experimental data to show, he showed some fantastic model simulations run on the ‘Blue Waters’ super computer. He has modeled all sorts of nanopores, including graphene layers which turn out to be quite ‘sticky’. He’s working with both Oxford Nanopore [http://blueseq.com/knowledgebank/emerging-technologies/oxford-nanopore-technologies/] and IBM [http://blueseq.com/knowledgebank/emerging-technologies/ibmroche454/]. Check out some of his animations here:

silicon: http://www.nsf.gov/discoveries/disc_videos.jsp?cntn_id=117318&media_id=67049&org=NSF
graphene: http://pubs.acs.org/doi/suppl/10.1021/nl301655d
nanopore capacitor: http://pubs.acs.org/doi/suppl/10.1021/nl071890k/suppl_file/nl071890ksi20070802_123247.mpg

Jingyue Ju is working with tagged nucleotides (with various PEG molecules acting as the tags, if I remember correctly). The DNA strand to be sequenced is processed by a polymerase which releases the tags as the nucleotides are incorporated. These tags are what are read by the nanopore. Genia announced last fall that they had switched their chemistry to use Dr. Ju’s system. When asked how long until he could sequence DNA, Dr. Ju answered “In a couple of months we’ll demonstrate real sequencing data”. Good news for Genia?
Massimiliano di Ventra talked about “Fast DNA Sequencing via Tunneling” – not exactly a nanopore, but definitely related. It looks a really cool technology, but unfortunately all he has to show at the moment is simulated data. Perhaps the most interesting thing is that he brought a new commercial sequencing company to my attention – he’s been working with Osaka-based Quantum Biosystems (a new one we’ll need to add to the ‘Emerging Technologies’ section of BlueSEQ’s Knowledge Bank.

NGS Year in Review Part 1: Promises, Promises

2013-03-14T18:38:00.000-07:00

In an annual ritual, the various NGS vendors gathered in Marco Island at AGBT to sell their wares and tout their technology to the eager attendees. I figured this makes it a good time to review what's happened over the past year. I’ll start by covering which promises were kept and which were broken, and follow up with subsequent posts on a more general overview of the progress we’ve seen, another one on the mergers that did and didn’t happen, and finish up with a post where I take a stab at what we'll see over the coming year.

2012 was a year of hope and promises. The NGS market is brutally competitive, with all the vendors trying to outdo each other, and 2012 was no exception. The major cycle of announcements that gives us a hint at what we were to see in the upcoming year starts with the JPMorgan Healthcare Conference and finishes with AGBT on Marco Island.

Last year Ion Torrent (Life Technologies) kicked everything off by announcing their new machine, the Proton. While many, myself included, groused that this new machine made a mockery of their slogan 'The chip is the machine', it was necessary for them to keep pace with their previous promise of improving outputs 10-fold every 6 months. The first Proton chip, the PI, was slated for mid-2012 and would generate 10Gb/run. Not bad, but it was the following PII chip, slated for the end of 2012, that caught everyone's attention. If it were to keep up the trend of 10-fold improvements, it would generate 100Gb of data in a few hours. Better yet, it would finally achieve the holy grail of NGS - the $1000 genome! But Ion Torrent didn’t quite pull it off. Despite making progress, their schedule has started to slip and the output specs are starting to look more meager. Combined, it means they didn’t hit the fabled $1000 genome in a day. Not even close. By the end of 2012 (and through AGBT 2013), their most advanced commercially available chip, the PI, generates around 10Gb of output per run. At $1000 per chip, it would cost around $9k and take up to a week to sequence a human genome. Getting better, but still not there. The chip they said would reach the goal, the PII, was first delayed to March 2013 and now to ‘mid-2013’. Also, rather than generating 100Gb at launch, they’re now talking about 32Gb/run at launch, climbing to 64Gb over time (probably about 12 months). So we might not see the “$1000 genome in a day” from Ion Torrent until mid-2014, or even a bit later.

Illumina got much closer to fulfilling their promises, but that’s partially because they weren’t so bold. While they did claim they’d have the ‘genome in a day’ by the end of 2012, they never said anything about what it would cost. The machine to perform this trick, the HiSeq 2500, was released and the official specs at the end of 2012 were pretty close – 27 hours for a 30X genome (90Gb). With recent improvements (especially on sample prep and analysis), they should be able to go from DNA to analyzed sequence in under 24 hours.

Ion Torrent and Illumina made their big announcements at the JP Morgan Healthcare conference, but Oxford Nanopore (ONT) saved their news for the more scientifically oriented AGBT meeting. And by all accounts, their short presentation stole the show and set Twitter afire. While they had already given us a peak at their upcoming GridION system, they started putting some specific numbers behind it, with the most dramatic being a 20-node system that by 2013 would sequence a genome in 15 min for ~$1000 ($10/Gb). Oh, and they gave a peak at some really intriguing data – 50kb reads with a 4% error rate (that would drop to 1% by the launch). But then they really stirred things up when they unveiled the MinION, a disposable handheld nanopore sequencer the size of a large USB stick, suitable for field work (including no need for sample prep), that would cost under $900 and generate over 1Gb of data. And both the GridION and MinION would launch in 2012. Nanopores were finally here! These claims were met with incredible excitement and even appeared to shake up the emerging NGS space by, allegedly, prompting Halcyon Molecular to close up shop.

Almost immediately, however, the cries of “Show me the data!” started to emerge from the ranks of scientists. As mid 2012 approached with no new data, the shouts became stronger. Some, myself included, held out hope when ONT was scheduled to appear at ASHG. A booth with pretty but non-functional demo units was all we got – still no data. When the agenda for AGBT 2013 came out, ONT was nowhere to be seen, so any hope of a last minute nanopore miracle vanished. But ONT did attend the show, and CTO Clive Brown gave an impromptu interview to noted blogger Nick Loman that seemed to reveal some of the issues that they were running into and a maybe/sorta indication of a 2013 launch (or at least data from early access customers). While many feel burned by ONT's undelivered promises, the truth is that all will be forgiven once they get their hands on a functioning nanopore sequencer. Book your tickets now for AGBT 2014.

[If you’d rather listen to me speak than read my words, Theral Timpson interviewed me about this over at Mendelspod.com]

2012 Will NOT be The Year of the $1000 Genome

2012-09-19T15:13:00.000-07:00

There was a lot of excitement earlier this year when Ion Torrent announced their newest machine, the Proton. It was going to let them continue down the path of rapid technology improvement and let them keep their oft-repeated statement of 10-fold improvement every 6 months. I was pretty skeptical of these claims when they first came out, but the PGM has done a remarkable job of backing them up, going from 10Mb on the 314 chip, to 100Mb on the 316 chip and finally to 1Gb on the 318 chip over a period of 12 months.

As impressive as Ion Torrent’s progress has been, there have been a few hiccups:

Contrary to their initial marketing slogan, the chip is no longer the machine. To keep riding the wave of improvements, you have to trade in your original PGM for a much more expensive (but still relatively cheap) Proton. Not surprisingly, there were some grumblings from customers when that little bombshell came out.
They have slipped a bit (by about 3 months) on their rapid pace of launching a new chip every 6 months. By their original plan, the PI should have come out in July, but we’re just now seeing it in September.
When the Proton was first announced, the PI was targeted for 10Gb, or 2 exomes per chip, and the PII was to offer 10 times the output which would be 100Gb, enough fo a single whole human genome (all for under $1000 for chip+reagents). The only problem is, they’re now redefining “whole human genome” to be 20X coverage, while the industry standard is more like 30X with some pushing for higher coverage of 40X or more. 20X coverage implies that the PII chip will initially only be generating 60Gb per run. Still quite impressive, but another slip from the original roadmap.

So, this means not only will we not have a whole genome on a single chip by the end of the year (due to the 3 month schedule slip), when we do get it, it won’t really be a ‘true’ whole genome run. You’ll probably need to run two chips (or a chip and a half, if you can manage that with indexing), meaning it will cost you more like $2k instead of the holy grail of $1k.

The other thing to note is that the launch of the PII will signal the end of the original ’10-fold improvement every 6 months’ promise. The follow-on chip, the PIII, will take a full 12 months after the launch of the PII, and it will only be about a 2X improvement instead of the 10X improvement we’ve been getting used to. Still, if they’re able to do what they say, by the middle of 2014 we’ll have the ability to generate ~200Gb in a 2-4 hour run for ~$1000. That, in turn, will surely put a lot of pressure on the market leader, Illumina, to launch some improvements of their own. Chemistry A and B, we’re waiting…

Complete Genomics is Bleeding to Death, $272 at a time

2012-08-08T18:40:00.000-07:00

When Complete Genomics launched their 'services only' NGS business model, many in the industry questioned whether or not it would work. The answer appears to be 'no'.

In their latest quarterly report they state that they delivered data on 2200 genomes and that they recorded $8.1M in 'cost of services' expenses while pulling in $8.7 in revenue, meaning their services business netted ~$600k, or $272 per genome. That's pretty meager earnings, but it gets worse. A lot worse. In addition to their 'cost of services' expense, they also have R&D expenses and sales/marketing expenses, which add up to $13.5M.

"But they can make up for it in volume, right?"

At the current rate, they would have to sell nearly 50,000 genomes per quarter to break even.

And they would have to be at the current price of $4000 per genome.

And they would have to somehow generate 25-fold more business without increasing their sales/marketing spend.

Which is why they're seeking 'strategic alternatives'. But who would want to buy a money losing business in a cutthroat market? Buyers might be interested in the IP (like their new 'Long Fragment Read' technology or their data analysis workflow), but I think the days of Complete Genomics' service business might be numbered.

LinkedIn Lamentations

2012-04-21T16:19:00.000-07:00

Lately, I seem to be getting a lot of connection requests on LinkedIn from people I don’t know (haven’t met, emailed or interacted with in any way that I can remember^*). I generally don’t connect with people on LinkedIn unless I’ve met them in person and worked with them a bit (or at least substantially interacted with them online), but that’s just me. Some people try to connect with as many people as possible, thinking this is somehow ‘networking’. Maybe if I were a recruiter I’d try to acquire as many contacts as possible, but as it is these strangers would just clog up my LinkedIn stream. So I press the ‘ignore’ button. A lot. It makes me feel a little guilty – kind of like slamming the door in someone’s face. But these people aren’t even trying. They aren’t introducing themselves or saying why they’d like to connect with me. Just a message that essentially says “Hi, you don’t know me, but please click this button.”

And while I’m being cranky about newfangled social media, what’s up with Facebook not letting me follow a link to an interesting article without giving them permission to tell everyone on the planet^** what I’m reading. I’m not interested in telling you about that and you shouldn’t be so interested in what I’m reading. What’s wrong with you, anyway?

So, back to LinkedIn. If you want to connect (and I don’t already know you), just tell me who you are and what you’re looking for. Despite what my friends say, I’m pretty nice and I might just help you out.

^*I am much older than my 41 years suggests, so perhaps it’s just dementia. If so, please just ignore this post. Who stole my socks?! It’s cold in here. I like pizza.

^**Yeah, that’s right. I’m selective about LinkedIn, but on Facebook I’ve friended everyone on the planet.

NGS Hype War

2011-12-23T13:08:00.000-08:00

Who’s winning the NGS hype war?

A few years ago it was PacBio – they were going to sequence a genome in 15 minutes. Currently it would take them >90 days and cost ~$225k. (They’re now more sensibly focusing on the advantages of long reads and directly reading modified nucleotides.)

Ion Torrent took over the reigns of ‘hype king’ with the launch of the Personal Genome Machine. They are building on the trillion dollar investments of the silicon wafer industry and promising 10x improvements every six months, to infinity and beyond! The most recent promise is a $1000 genome in two hours in 2012. In all fairness, they’ve kept up their promises over the past 12 months. The “10MB” 314 chip is now producing up to 40MB. They launched the 10x improved “100MB” 316 chip over the summer, and it’s now routinely generating >200MB of data. The “1GB” 318 chip hasn’t launched yet, but it seems reasonable that they’ll be able to hit their target. I haven’t heard anything about their next chip (what would/could be the 320 chip), but I suspect they’ll have lots to say at Marco Island.

So Ion Torrent is clearly currently winning the hype war, but is there a contender? Mabye.

Genia is a new start-up out of Menlo Park. They’re talking about the $100 genome (the $1000 genome is so 2011) and they’re calling themselves the “Last-Gen Sequencing” company. Apparently their technology is so revolutionary there won’t be a need for anything else. Just a heads up to anyone else developing their own technology, you might as well stop. Genia’s got it covered. No, they don’t have any instruments to sell just yet. And, no, they technically haven’t actually produced any sequence yet. But just you wait. They hype has just begun!

What's the NGS Buzz?

2011-09-30T16:10:00.000-07:00

There's been quite a bit of 'next-gen' sequencing news lately (some of it positive, some of it pretty negative). I thought I'd take a stab at ranking them in terms of their "buzz" - how much people are talking about them, excitement around updates, etc. It is very subjective and definitely NOT an attempt at ranking their usefulness/performance (which would be highly application specific). Feel free to let me know how wrong I am in the comments section.

(I inexplicably left out Complete Genomics - now corrected)

Platform	Comments	Buzz Factor	Trend
Ion Torrent	Lots of promises, excitement and chatter Lots of blogs analyzing data	10
MiSeq	Data starting to trickle out Mostly in a battle with Ion Torrent	6
GnuBio	Completely backed off their "$30 WGS" claims Interest picking back up now that they're in beta testing	5
Complete Genomics	Still in the news, in a death battle with ILMN and BGI	5
HiSeq	Dominant (if boring) NGS workhorse	4
Oxford Nanopore	Not much news Initial excitement waning Waiting for next (first?) big announcement	3
Pacific Biosciences	Only news is bad news Management overestimated market adoption of PacBio Laid off 28% of workforce (ouch!)	3
SOLiD	Has become the ugly stepsister of Ion Torrent Management says "putting all chips into Ion Torrent" and "(light based seq) is nearing the end"	2
454	Not a lot of news since FLX+ Not much in the way of public discussion	2

Helicos Cries Out “I'm Not Dead! I'm Getting Better!”

2011-08-29T15:25:00.000-07:00

Helicos, the first company to launch a single molecule DNA sequencer (a class sometimes called “3^rd Generation”), has been hanging on to a thread for a while. They've been delisted from NASDAQ and their cash supply is dwindling (down to $1.6M as by June 30^th). They are going through another round of cash-saving layoffs that will bring their headcount down to 10. They have apparently stopped selling the HeliScope and their ability to supply reagents and service support to their current customers has been called into question.

When they launched their HeliScope in 2009, they went head to head with the more established players (Illumina, ABI and 454) focusing almost exclusively on being the first 'true single molecule sequencer' for genomic sequencing. It was a tough sell given that they were a bit late to the party and that their reads are shorter and have a higher error rate. They might have been better served to focus on RNA-Seq and ChIP-Seq where the lower quality reads wouldn't have hurt as much and they could have touted their (at the time) industry-leading # of reads per run.

For the past few months their main strategy seemed to center around litigation – they're suing Life Technologies, Illumina and Pacific Biosciences for patent infringement. Just recently, however, they've expanded this strategy by borrowing a page from Complete Genomics – they have launched a sequencing services program to increase their revenues. They've also launched an interesting targeted sequencing solution in which the capture sequences are attached directly to the flow cell (rather than their standard poly dT sequences). They've demonstrated this technology by creating a flow cell for the direct sequencing of the BRCA1 gene.

I fear it may be a bit too little too late, but at least Helicos is still kicking and demonstrating that it doesn't want to go on the cart.

Ion Torrent's Roadmap to the $500 Genome

2011-08-12T17:49:00.000-07:00

Ion Torrent has made some bold claims about making 10x improvements every 6 months, and so far they've kept to that schedule (albeit only over a single 6 month period). In a recent Nature paper (covered by In Sequence 7/26/11) they detailed how they could shrink their features and increase the chip size to achieve first 165M and then 1100M sensors per chip. I've used this information, along with some really useful 'real world' feedback on the 314 and 316 chip from Nick Loman's blog (@pathogenomenick), to create a speculative roadmap for how Ion Torrent might achieve the 10x improvements through the middle of 2013. Assuming they are able to achieve the higher density chips in the timeframe I've listed (I don't think any timeframe was listed in the paper), that they can extend their reads out to 1000b (which seems reasonable given where 454 is today) and that they can improve the number of 'effective beads' (based on fill efficiency, # of 'live' beads, and # of reads passing the filters), it doesn't seem too unreasonable that they might maintain their '10x improvements every 6 months' goal out through the middle of 2013.

I also took a stab at what future chips might cost based on Rothberg's statement that they would hit a $1000 genome by 1/1/13 and a $500 genome by 7/1/13 (In Sequence 6/14/11). I'm assuming 90Gb per genome and $250 in reagents per run. (The prices listed are the initial prices at launch, but they've already demonstrated that the prices for 'old' chips may come down once the new chips are released.) Everything seems pretty reasonable until you get out to the (theoretical) 324 chip at $5000. Since Rothberg only predicted a 2x drop in price/genome from 1/1/13 to 7/1/13, they're either going to charge a lot more for this chip, or the 10x improvements will have started to peter out.

It should be fun to see how accurate this roadmap is. As always, comments and criticisms are welcome.

Chip¹	Release Date	Output Spec	Sensors	Fill Eff. ²	Live Beads	Passing Filter	Read length	Calc Output	Est. Chip Price
314	01/01/11	10Mb	1.2M	41%	67%	67%	100	20Mb	$250
316	07/01/11	100Mb	6.1M	80%	67%	67%	100	200Mb	$250
318	01/01/12	1Gb	11M	80%	67%	67%	250	1Gb	$500
320	07/01/12	10Gb	60M³	80%	67%	67%	400	10Gb	$?
322	01/01/13	100Gb	165M	100%	100%	100%	600	100Gb	~$750
324	07/01/13	1Tb	1100M	100%	100%	100%	1000	1Tb	~$5,000

¹The chip names 320, 322, and 324 and release dates are purely speculative. I haven't seen Ion Torrent claim a new chip every 6 months, just that there would be 10x improvements every 6 months.
²The 'fill efficiency', 'live beads' and 'passing filter' metrics for the 314 and 316 chips came from Nick Loman. The values for the other chips are pure speculation on my part. The values for the 322 and 324 chips are surely a little optimistic, but they could be counterbalanced with longer reads to achieve the same output.
³The 60M sensor chip is also pure speculation on my part. Ion Torrent didn't mention this 'intermediate' chip in the Nature paper.

The Institute That Never Was...

2011-07-21T15:10:00.000-07:00

In early January 2010 Illumina made a big announcment – BGI was to purchase 128 of Illumina's brand new HiSeq 2000 sequencers. (In Sequence 1/12/10). Not to be outdone, Life Technologies followed up with their own announcement a couple of weeks later – the 'not quite yet formed' Ignite Institute was to purchase 100 of Life's brand new SOLiD 4 sequencers. (Genome Web 1/28/10)

Inside Illumina there was a lot of skepticism (myself included) about Life's announcement. It just seemed like a desperate ploy to detract attention from the BGI announcement. In the back of my mind, however, I wondered if I was being too pessimistic in my Kool-Aid drinking. Turns out the answer was 'not so much'.

Ignite ran into a number of troubles with funding and the purchases never happened. In fact, Ignite never 'happened'. Instead it sort of merged with the Fox Chase Cancer during the formation of the 'Cancer Genome Institute at Fox Chase'. Perhaps most telling was that when Fox Chase forged their own partnership with Life the 'Ignite' name wasn't mentioned. As quoted in Kevin Davies article:

“We didn’t mention Ignite [when that was announced] – that was intentional,” Boyd explains. “We got tired of negative reporters who want to dig into what happened to Ignite [in Northern Virginia] and dredge up that experience.”

Negative experience, indeed!

As for BGI, they certainly still exist and they've actually purchased all 128 HiSeq 2000's (plus a few more). And they continue to draw strong reactions - praise, scorn and fear, to name a few.

(Lest anyone think I'm unfairly picking on Life, Illumina has been known to make a stumble or two. I'm looking at you, Avantome ;-)

Explaining BlueSEQ

2011-06-09T16:39:00.000-07:00

This is my (non-snarky) attempt to convince Anthony Fejes that BlueSEQ might be a good idea.

Anthony Fejes, in the process of doing a phenomenal job with realtime blogging about the Copenhagenomics talks, expressed his concerns and doubts about BlueSEQ's business plan. For those of you who don't know, BlueSEQ is a Danish startup which is attempting to create a neutral next generation sequencing exchange. Their goal is to match researchers who have a sequencing project need with service providers who have excess capacity on their sequencers.

Take a minute to read Anthony's comments (but please come back when you're done).

His main concerns seem to be:
1) Why would service providers want to participate?
2) How can BlueSEQ standardize NGS in a meaningful way?

Let's tackle the first point. Why would providers want to be a part of this? I'll give you my opinions, but the simple fact is they ARE interested. BlueSEQ has already signed up over 20 providers and they're getting more requests all the time. Providers really want to have access to these customers to help them drive and expand their business. It also helps them optimize their workflow. For example, if they're in the middle of a large human genome resequencing project and they've got an internal user who wants to run a 5 sample small RNA-Seq experiment, they could outsource the small project so as to not interrupt the large project (which would require a completely different setup). Alternatively, if they're running some ChIP-Seq projects, they may want to go onto the exchange to find as many ChIP-Seq samples to help fill up an entire 5500xl SOLiD or HiSeq 2000 run. Basically, it gives them more customers and more flexibility.

Now to the second point. Anthony correctly points out the folly of trying to standardize such things as the bioinformatics analysis process. Fortunately that's not what BlueSEQ is trying to do. In talking with dozens of service providers, what they've found is that a big issue that the providers face is educating their potential customers about what NGS can and can't do and translating the customer's general idea of a biological experiment into a particular NGS protocol. This is where BlueSEQ can step in. The goal is to help guide researchers in communicating their needs to the providers. For example, translating something like "I want to compare gene expression levels between these 10 samples" into something like "Starting from 100ng of total RNA, I need to run RNA-Seq (including library prep) on 10 mouse samples with 50M 1x100bp reads per sample, followed up with an analysis that looks for both expression level differences as well as SNP variances". The final details would likely be worked out between the researcher and the provider, but they would at least be on the same page.

If you're still with me, here are my quick responses to the rest of Anthony's specific questions:

[This is one stop shopping for next-gen sequencing providers? How do you make money doing this?]
BlueSEQ makes money by charging service provider small fee (generally 5-10%, depending on the project size) when, and only when, the provider wins a bid.

[How do you standardize the bioinformatics? Seems... naive.]
Yes, that would be naive, but they're not trying to do that.

[again, why would providers want to opt in to this?]
Because they want more business. Of course, if a service provider is running their machines 24x7, they wouldn't want to join. However, it appears that most providers don't find themselves in this situation.

[Why would any provider want customer reviews of NGS data... ]
It's possible they wouldn't, especially if they're not very good. But this is really more for the users as over time it will help them pick the best providers (and not, for example, choose simply based on price).

[the sample prep is a huge part of the quality, and if they don't control it, it's just going to be disaster.]
This would be entirely up to the researcher and provider. Some providers want that level of control (to ensure high quality) while others are happy to have their customers prepare the libraries.

Retirement Fail...

2011-05-05T16:12:00.000-07:00

Well, I find myself a little less retired than I expected to be. My intention was to take a good long break before looking for something interesting. It seems, however, that something interesting has found me. I'm doing some work for a Danish startup called BlueSEQ.

They're setting up a sequencing service exchange. If you've got a sequencing project but no sequencer (or not enough capacity) you can put your project on the exchange and compare the various bids (to get the best price, right platform for the job, level of expertise you need, etc.) If you're a service provider or core lab with excess sequencing capacity you can bid for projects to keep your pipeline full. The service is free for researchers while the service providers pay a small service fee (but only for successful bids).

The best part is that the whole process is centered around the Project Design Tool. It takes researchers step by step through the process of describing their experimental needs, ensuring that both the researcher and the service provider are on the same page and everybody is getting exactly what they expected. The project designs can be saved and reused for future projects to maintain consistency.

So where do I come in? I'm developing the BlueSEQ NGS Knowledge Bank, a neutral repository of all things next gen sequencing. I've got the basics up now with general descriptions of the major platforms and applications as well as a list of NGS-focused conferences and meetings. Have a look and tell me what you think. I'd love to hear your thoughts about what's there now and what you'd like to see in the future.

Check out the official press release from BlueSEQ.

Ion Torrent's Tilt-Shift View of the Future

2011-03-31T14:21:00.000-07:00

What does tilt-shift photography have to do with Ion Torrent? Yesterday I would have said "nothing", but then they released a video that is apparently dedicated to it. Don't get me wrong, it's a really cool effect that makes everything look miniature, but I'm struggling to figure out what it has to do with next gen sequencing. The PGM acts as an iPod cradle; maybe it also doubles as a camera?

For your enjoyment, a pointless but cool video:

Ion Torrent's $1 Trillion Investment

2011-03-14T21:59:00.000-07:00

Ion Torrent has a new video out (see link below). In addition to reminding everyone that they're building on the $1 Trillion investment made in the semiconductor industry (not exactly sure how relevant that is), they also show images of the 314 and 316 wafers. From the images, it looks like the 316 chips are roughly 5x the size of the 314 chips (~74 chips/wafer for the 316 chip vs ~350 chips/wafer for the 314 chip). That more or less fits in with the 5x increase in number of sensors/chip (1.2M vs 6M). It's impressive that this 5-fold size increase only resulted in a 2-fold price increase ($250 to $500). Their next chip, the 318 which is slated for 4Q2011, will roughly double the number of sensors to 11M while holding the price at $500. If they have to keep increasing the size of the new chips, it seems like it will be difficult to keep the price at the current level. It will be interesting to see if they start increasing sensor density rather than just chip size.

Ion Torrent's video

Riveting ad copy

2011-03-06T21:31:00.000-08:00

Here is 454's latest ad for the GS Junior...

...with some absolutely scintillating copy...

"The PicoTiterPlate (PTP) device is placed in the Bead Deposition Device (BDD) in preparation for pipetting beads onto the PTP. The PTP remains in the BDD until ready for sequencing."

Nothing like a few TLAs to spice up your ad. Riveting!

Creepy Ad

2011-02-18T12:12:00.000-08:00

Ok, there's something about this ad (for Vetter Pharma in the most recent issue of BioPharm International) that creeps me out. It's either because she's smiling even though someone's about to jam a big needle in her arm or because she has sort of a “I'm going to rip your arm off if you poke me with that needle” kind of smile. Either way, I don't want Vetter to jab me with any needles. Or her to rip my arm off.

AGBT's biggest loser was...

2011-02-16T19:01:00.000-08:00

Twitter!

Seriously, the AGBT organizers appeared to be caught off guard by the popularity of tweeting/blogging about the various talks. Many thanks to the presenters who allowed tweeting and to the many attendees who took the time to tweet and blog about them. I found it enormously helpful as it allowed me to attend the meeting vicariously. I've listed some of the blog resources at the end (which also contain good info on the research talks).

The general consensus seems to be that the meeting was good but that there really wasn't anything groundbreaking this year. The commercial players either already announced their good news back in January, had nothing to say or weren't ready to say anything just yet.

The Established Players:

Illumina

There really was nothing new for the meeting as they had already announced the program for achieving 600GB with HiSeq2000, the internal 1TB runs and the new MiSeq platform. Illumina was a fairly popular tweet/blog topic (second highest coverage) with most people either focusing on MiSeq, HiSeq's data output or Illumina's general market dominance. The only real negative that came up was the run failure rate at Harvard. Illumina had a moderate presence in the twitterverse, sending out an average # of tweets to attendees.

Life/SOLiD

Like Illumina, they didn't really have anything new to say about their SOLiD platform. They were, however, the king of the tweets, sending out more than all of the other sequencing vendors combined. The attendees weren't quite so vocal. Combining tweets for both SOLiD and Ion Torrent (see below), they had just the third highest coverage. As for news, it seems that Life is really starting to position SOLiD as system of choice for the cancer genome market.

Complete Genomics

Bucking the trend, Complete Genomics did save some big news for the meeting. They have created a public database containing 40 complete genomes with the promise of 20 more in March. The company tweeted an average amount and received some back (#4), most of which was excitement around the public dataset.

454/Roche

Hello? Does anyone have anything to say about 454? <crickets>. Nothing directly from the company and just a handful of tweets from the attendees. Maybe next year?

The Hopefuls:

Life/Ion Torrent

Life didn't really have any announcements about Ion Torrent, but people were eager to see the data in the presentations. They seemed pleased with the low GC bias but perhaps a little disappointed with the error rates.

PacBio

The company didn't send out any tweets, but they win the prize for the greatest interest from the twitterverse – almost double the #2 tweet getter. However, a big chunk of that was about the movie they showed (which some described as too simplistic for the AGBT audience while others described it as a giant 30 min ad for PacBio).

Oxford Nanopore

ONP tweeted an average amount, but they didn't have any big announcements. There wasn't too much tweeting about them since no one has their hands on this instrument yet, but those who did comment seemed quite positive about their GridION system and were eager to see some real data.

BioNanomatrix

Nothing from the company, but a few people out there were eager to see how this system will perform.

NABSys

About the same – nothing much out there yet, but some are waiting.

The Head Scratcher:

Agilent

Agilent was the “Gold” sponsor (just below Life, which nabbed “Platinum”) - something that costs big bucks (around $100k, I think). However, at least in the twitterverse and the blogosphere, they were just about a non-entity. There were no official tweets from the company and their only announcement was about their new RNA target enrichment kit. A nice addition to the market, but I'm not sure if that news was worthy of the gold sponsorship purchase.

AGBT Summaries (a big thanks to you all!):

Keith Robison at Omics! Omics!

Prithwish at Omically Speaking (part 1, part 2)

Kevin Davies of BioIT World at NGSLeaders

J Ireland at 5AM

A Torrent of Improvements

2011-02-10T21:13:00.000-08:00

The news from AGBT this year seemed a little tame (more on that in a future post), but there was one statement that really caught my eye. Ion Torrent said that researchers can expect a 10x improvement in sequencing output from the PGM every 6 months through the release of new chips (like the recent update from the 314 to the 316 chip). That's a fairly extraordinary claim. If true, it means that by next year's AGBT meeting their machine will be producing 10GB per run and that by AGBT 2013 they'll be producing 1TB per run (Illumina's current internal output on the most juiced up HiSeq2000).

Jay Flatley recently recounted Illumina's tremendous pace, going from 1GB per run to over 1TB per run in 4 years. If Ion Torrent is able to deliver on their claim, they would make up the same ground in just 18 months. It will be interesting to see if they can continue improving the PGM at this pace for an extended period of time.

Lifting the Nano Curtain

2011-02-01T17:09:00.000-08:00

Late last week Oxford Nanopore, a next gen sequencing company which has been in stealth mode for the past couple of years, gave us a little peek at what they've been working on. As a nanopore-based technology, we already knew it would probably have long reads and minimal reagent requirements. What's really interesting is the form factor of the instruments. Not only are they inexpensive (prices haven't been stated, but the consensus seems to be around $50k), but they're really small and they can be combined into sequencing "networks". Daniel MacArthur, Luke Jostins and Kevin Davies have all written up nice summaries on the technology and how they think it will be used.

In addition to previewing what looks like some pretty cool (and remarkably polished) technology, they're revealing some nice marketing moves as well. First, they've published four very slick videos describing their technology (see below). Second, they've timed their announcement very well as it was just a few days ahead of AGBT, the "biggest" (well, most significant, anyway) sequencing technology conference. Despite not being a sponsor of the meeting, they're sure to generate a lot of buzz. That's a great way to stretch a marketing budget.

Hopefully we'll hear more after AGBT starts rolling this week.

The GridION system: part 1 from Oxford Nanopore on Vimeo.

The GridION system: Part 2, advanced workflows from Oxford Nanopore on Vimeo.

Nanopore sequencing from Oxford Nanopore on Vimeo.

Exonuclease sequencing from Oxford Nanopore on Vimeo.

A New Sequencing Player?

2011-01-24T10:15:00.000-08:00

My interest was piqued when I saw the headline "PerkinElmer Steps into DNA Sequencing Market" from Genetic Engineering News. Was another major player entering the crowded market of next gen sequencing? (Reading, reading...). Hmm, no, it looks like they're offering services (reading some more). Ah, here it is, their business model:

"PerkinElmer’s model follows Complete Genomics, Illumina, and BGI (formerly known as Beijing Genomics Institute), wherein companies provide sequencing as a service rather than developing and launching competing sequencing platforms that scientists must buy to conduct sequencing projects on their own."

What? GEN is somehow equating the PE business model to ALL of the following:
Complete Genomics - "services only" using their own proprietary platform
Illumina - dominant next gen sequencing platform provider which happens of offer services as a small part of their business
BGI - standard, albeit stupendously large, service provider which primarily uses Illumina's platform

So, which one is it? Well, it's nothing more than yet another sequencing service provider using Illumina's HiSeq2000 instruments, which makes them pretty much like any of the dozen or so services providers listed here (and these are just the certified providers). So, they're sort of like BGI. Except to the best of my knowledge they haven't purchased 128 HiSeq instruments and they haven't stated that they'll sequence anything that's "tasty or cute".

Cool vs Playskool

2011-01-22T18:30:00.000-08:00

Is it just me, or does the PGM from Ion Torrent kind of look like a children's toy?
To get everyone on the same page, here is a toy:

A Toy

Now, here is the PGM:

Ion Torrent's Personal Genome Machine - could be a toy, can't tell for sure

And compare that to the newly announced stylish MiSeq from Illumina:

Illumina's MiSeq - clearly not a toy

Sure, sure, the MiSeq doesn't actually exist yet and I'm sure there will be plenty of debate about which machine will outperform the other, but Illumina is clearly winning in the looks department.