Wednesday, February 26, 2020

MGI Deconstructs the Sequencer

At some fancy restaurants one can get a "deconstructed dish".  As I understand it, as I don't frequent such restaurants, a deconstructed BLT would have the bread, bacon, lettuce and tomato each as their own individual item, but prepared in a novel way which highlights the strengths of each ingredient.  When I got a preview last night of Rade Drmanac's closing AGBT talk on achieving a $100 human genome (reagents price only), that was the vision I had: Drmanac and his team have created their Tx system by deconstructing the optical high throughput sequencing-by-synthesis instrument.

Saturday, February 22, 2020

CoolMPS Revealed

Having summarized MGI's announcement they are launching into the U.S. market this spring and started digging into the performance characteristics of MGI's instrument lineup, let us now turn to their BioRxiv pre-print on the CoolMPS chemistry, as it has many useful technical details.

MGI Dual Drop of CoolMPS News Ahead of AGBT

Friday morning I got excited because a preprint showed up at BioRxiv detailing the CoolMPS sequencing technology from MGI (aka BGI aka Complete Genomics).  First announced in Fall 2018, this approach sounded, well, cool.  Using fluorescently labeled antibodies specific to each reversible terminator seemed like a crazy pipe dream.  So getting a good look at it in a manuscript is an event!  But then Friday afternoon MGI had a second big pre-AGBT reveal: launch of their sequencing systems in the U.S. later this year. Below is a quick run-down of the sequencer announcement; the pre-print has many details I'm still parsing.

Thursday, February 20, 2020

A Lazy Look at The Field of Sequencing Startups

AGBT looms ahead of me next week which serves as impetus to let fly an idea I've had simmering for a while: to look at sequencing startups by a particular type of information they choose to reveal.  I'm not expecting any big announcements at AGBT from this space, though would be thrilled to be surprised.  But there is the risk of getting contaminated with some on-the-sly scuttlebutt, so better to get this done now.  By the way, in the full disclosure category, I have consulted for a few companies here and have NDAs either on my own or via employers; everything here is based on public information.

Tuesday, February 18, 2020

Skimming Seq

My last post discussed BioJulia in the face of a challenge from the new Seq programming language.  Tonight I'm going to take a bit more of a look at Seq itself and touch on both why I'm tempted to try it and why I remain reticent to do so.  I hope if any of the Seq team sees this they will regard it as some parts constructive criticism and some parts market feedback.

Thursday, February 13, 2020

A Short Master Class in Benchmarking

There's a blog post on BioJulia.net that is well worth reading, even if you don't use Julia or I'd argue if you don't actually program.  It looks at an issue of performance that was raised with BioJulia and with fierce but respectful passion examines the critique and explores just why BioJulia didn't perform well in the comparison.  In the end, this triggers a code review and a huge speed increase in the problematic areas -- which will widely benefit BioJulia users.

Tuesday, February 11, 2020

Sampling Current & Future Directions in PCR Diagnostics

My qPCR explainer seems to have done relatively well, though it took some refinement after readers caught a number of errors.  The most embarrassing of those is that I got my PCR ramp units upside down, so instead of 4 seconds or so per degree C it's degrees C per second so my times were off by a factor of 16! Ouch!  Despite that miscue, I'm here going to explore some of the variants on PCR that are out there, including some that are being employed searching for the newly renamed COVID-19 virus.  Included here are some of my own speculations and musings, so as always remember I'm someone who thinks about these things and sometimes talks other people into running them, but I haven't set up a PCR in 8 years.  Also, the field of PCR variations for diagnostics is enormous and I don't claim to have anything near complete knowledge of it, so this should be seen as a sampler and not a comprehensive review.  Also, the usual reminder I am a paid consultant for a diagnostics company but they are neither aiming at viruses nor using PCR, so I won't discuss them -- but if you feel that shifts your priors on how I treat other companies you have the information to do so.

Saturday, February 01, 2020

A qPCR (aka RT-PCR aka rRT-PCR) Explainer

I've gotten in a number of Twitter threads and seen a lot of Quora questions about the qPCR test for the Wuhan coronavirus that I realized would really be best handled by writing an explainer. I'm intending it for financial types, reporters and anyone from the lay public interested in learning a bit more.   For most regular readers of this blog, there won't be anything new to you.  If you'd check me for accuracy, I'd be grateful but perhaps many will skip over this one.  That also means I going to try to resist my usual urges to make lighthearted references to popular culture; they're a good way to be confusing.

Thursday, January 30, 2020

Can ONT Maintain Grip on Burgeoning Flowcell Herd?

A notion dawned on me when I was mentally planning my write-up of the Nanopore Community Meeting, but I decided to put off fleshing it out until a later date.  After a bit of procrastination plus a crush of other ideas, here it is: Oxford Nanopore flowcell lineup has been a bit complicated for a while, but it's probably going to get worse.  There's always been serious issues with the current level of complexity and it's hard to believe this will do anything but escalate.

Monday, January 27, 2020

An Ultimately Tufnellian Look At Oxford Nanopore R10.0 Homopolymer Performance

Homopolymeric sequences have never been easy for any sequencing platform, but single molecule sequencers struggle the most with this.  Oxford Nanopore has made remarkable strides in both raw an consensus accuracy via chemistry and software improvements, but still is challenged by systematic problems with homopolymers.  The R10 series of pores is intended to significantly improve performance by having a longer narrow region to interact with more bases, and at the Nanopore Community Meeting there were several slides touting improved performance.  Nanopore's slides have an X-axis that goes to 8.  By happy circumstance, around that time we generated a large dataset on R10 and got results very similar to ONT's.  Plus there's a dataset available from Mads Albertsen's group to support their updated pre-print on using Unique Molecular Identifiers (UMIs) to generate high quality consensus sequences.  But our internal dataset is  the best, as ours goes to eleven!

Sunday, January 26, 2020

UST Bets on TELL-Seq

I've made a few references recently to TELL-Seq, both in my flawed analysis of BioNano Genomics (I missed a key business development in their raising $18M in October; I stand by the science comments and fear that the fund raise buys them about a year of time) and on 10X Genomics discontinuing their genome assay kits.  Now to actually dig into that technology -- a bit late given the preprint came out last fall, but better late than never.  So put on your sunglasses and hoodies, conjure up the image of early television chefs and key up the theme music for The Lone Ranger, because here I go.

Thursday, January 23, 2020

Can BioNano Genomics Map A Way Past Twin Perils?

When playing with the structure of this piece in my mind, it occurred to me that Norman Maclean's thoughts about fly fishing apply just as well to biotechnology companies
It is also interesting that thoughts about fishing are often carried on in dialogue form where Hope and Fear -- or, many times, two Fears -- try to outweigh each other
The executive team at BioNano Genomics may well be gripped by this situation, as they are faced with two great perils: their finances and their markets.

Wednesday, January 22, 2020

Genia: It's Alive!

Once in a while I get the thrill of someone sending me a really good tip - that surge that comes with knowing that I know something that most people don't.  That rush of knowing that soon I'll get to spill the beans.  It's great, even if it upends my widely disseminated opinions.  Even if a moment later I realize that if I had thought harder I would have unearthed the nugget on my own.  All of which is the case here -- my tea leaf reading that Roche partnering with Illumina on diagnostics indicated that Genia is no more -- well, that interpretation is no more.  Because I got a hot and verifiable tip that Genia is very much still an active project at Roche.  And the verification is how I could I found this independently.

Sunday, January 19, 2020

10X Genomics Exits Genomes

10X Genomics original product was a kit for generating linked reads from genomic DNA.  The idea had been kicking around for a while, partitioning long DNA into compartments and generating tagged libraries from each compartment.  This enabled both genome assembly and haplotyping from very small amounts of DNA.  When first reviewing 10X's slides from J.P. Morgan I had this thought "where's the genome kits" but then forgot to include it in my write-up.  Now I'm even more chagrined to discover that the explanation had been posted days before the conference: 10X has told their customers that their genome library kits are in the process of being discontinued.

Friday, January 17, 2020

JPM20 Loose Ends: Agilent, ThermoFisher, 10X Genomics, NanoString - plus PacBio & ONT

Time to close out  J.P. Morgan season with a grab bag of kvetches and kibbitzing on multiple 'omics companies that presented.  Much of this has been stimulated by Twitter discussions, with particular credit going to Varro Analytics and Albert Vilella.   While I've never been to J.P. Morgan physically and am skeptical I'll ever go, reviewing all this is a great prep for AGBT -- which I'm happy to be returning to this year for it's last Marco Island appearance for many years (forever?).

Tuesday, January 14, 2020

Bold Genapsys Talk at JPM20

Genapsys' CEO Hesaam Esfandyarpour presented today at the JPM Morgan Conference and delivered an expansive vision of where the company is going both this year an the long term.  This includes planned commercial launch of the 144M chip this year, an aggressive expansion into international markets and another round of "pre-IPO" financing.

Monday, January 13, 2020

JPM20: Roche Links with Illumina On Diagnostics

Another bit of Illumina news released at J.P. Morgan today is that Roche Diagnostics is partnering with Illumina.  The 15 year partnership (same duration as with QIAGEN) will place Roche diagnostic assays on Illumina clinical-grade sequencers as well as the two will jointly work for regulatory approval of Illumina's TruSight Oncology assays.  Roche has extensive experience in oncology, particularly since they own Foundation Medicine. This suggests that Roche is happy with a two pronged strategy in oncology diagnostics, selling assays on their own through the partnership while their Foundation arm offers an all-in service.   But it also stirs the tea leaves in the genomics M&A pot.

JPM20: Illumina Launches Super Resolution Instruments

Illumina presented this morning at the J.P. Morgan Healthcare Conference (presentation, slides & breakout).  For us sequencing geeks, the biggest news is the launch of a pair of new sequencers -- but not where either myself or Shawn Baker anticipated.  Rather than doing something about the low end of their line (as I predicted) or replacing the MiSeq as Shawn guessed, Illumina perceived a need for desktop instruments to span the range between the existing NextSeq 550 and the NovaSeq and has christened the new instruments NextSeq 1000 and NextSeq 2000.  They also come with some slick new technologies embedded.

Sunday, January 12, 2020

Is Illumina Vulnerable At The Bottom?

According to both the FTC and CMA, Illumina holds a nearly complete monopoly on the sequencing market, with other players (Ion Torrent, Oxford Nanopore) holding on to toehold niches.  Illumina has held that position for an extended period, so what might upset it?  I'm going to explore the case that they may have some serious inroads at the bottom of their line.

Thursday, January 09, 2020

Might Illumina Shave NovaSeq Run Times?

I've had some people asking, either privately or via Twitter, what might come from Illumina next week at JP Morgan (8:30 am PST on Monday).  I have another post in the works (ideally going out not long after this one) on one aspect of their business, but then I thought of something else.  Something in the great tradition of proposing a plan while being quite unaware of all the critical details that the plan relies on!

Sunday, January 05, 2020

A Le Mans for Clinical Genomics?

If you haven't seen Ford v Ferrari (or Le Mans '66 in parts of Europe), I strongly suggest you do so if it is still in a local theater.  I'm neither a gearhead nor a fan of watching automobile races, but while the movie is centered on an attempt to win the  1966 24 Hours at Le Mans, there is so much more going on.  Designer Carroll Shelby (Matt Damon) must not only project manage a difficult task, but also deal with unreliable allies (as one wag put it, the biggest villain in the title isn't Ferrari) and a cantankerous star driver named Ken Miles (Christian Bale).  One touching aspect of the movie is the portrayal of Miles' relationship with his young son, an audience proxy who idolizes but sees all sides of his father.  

Thursday, January 02, 2020

Illumina & PacBio Throw In The Towel

I had planned to post this morning a "preview of 2020" piece I had drafted in my head on the ski slopes the previous two days, but never got around to actually committing it to bits and bytes.  Today's announcement that the Pacific Biosciences acquisition from Illumina is officially dead means the first item of that piece is mostly going uncaptured.