Tuesday, March 02, 2021

AGBT21: VizGen Unveils MERSCOPE

More spatial profiling news coming in from AGBT -- Harvard spin-out VizGen is launching in the U.S. an instrument implementing MERFISH technology.  This sub-$300K instrument will initially enable panels of up to 500 genes to be profiled, with plans to expand that capacity to 1000.  Users either pick from a menu of pre-designed panels or select genes using a Gene Panel Design Tool and VizGen would proceed to manufacturing the panel in around two weeks.  VizGen CEO Terry Lo and Senior Director of Marketing Brittany Auclair were kind enough to give me a preview last Friday.

Monday, March 01, 2021

AGBT21: The LabRoots Presentation Platform is an Unmitigated Disaster

Rant is ON! I've been having an utterly miserable experience with the LabRoots conference software that AGBT is using for their virtual meeting.  This year has exposed many of us to a wide variety of teleconference and virtual meeting software and many of the glitches are small and hard to pin down.  Or matters of personal preference (though if you don't share mine, you are simply wrong!).  But now on two major platforms I've come across major issues with LabRoots

AGBT21: Rebus Esper for Spatial Sees Things You Wouldn't Believe

My prediction that spatial would be a hot topic at AGBT was easy to make knowing I was sitting on embargoed news in the spatial space.  This morning Rebus Biosystems announced the launch of the Rebus Esper system for wide field spatial profiling of gene panels with subcellular resolution.  Rebus is promising that this instrument will offer true walkaway automation from fluidics through imaging, and data processing, requiring only one hour of hands-on time.

AGBT21: A Few Pre-Conference Mutterings

Getting some miscellanea out before AGBT21 starts later this morning

Sunday, February 28, 2021

AGBT 2021: A Spatial Foundation

I'll call it now -- the big buzz at this year's AGBT will be around spatial profiling.  Trust me, it's not just a hunch.  The two current players in the field -- nanoString and 10X Genomics -- both have significant presence in the virtual conference.  Don't be surprised to see more players on the field -- just sayin'

Saturday, February 27, 2021

PacBio With SoftBank's $900M: How Might TheyWork?

Pacific Biosciences continued its roll of successful business development, snagging $900M from Japan's SoftBank two weeks ago.  Combined with a recent secondary stock offering and a major deal with Invitae, PacBio has gone from their self-proclaimed near-derelict status during the Illumina acquisition attempt saga to rolling in cash.

Friday, February 26, 2021

More Details on 10X's Sample Profiling Trident

10X Genomics had an online event Wednesday called Xperience (as far as I could tell no Jimmy Hendrix music was used, a missed opportunity!) to lay out their development roadmap.  This largely paralleled the presentation given at J.P. Morgan, but there were a few new bits and of course much more technical detail to whet the appetites of scientists -- and judging from a number of very positive tweets I saw today they were successful in that goal. Some of the 10X management was kind enough to walk me through the deck earlier this week as well as permission to borrow images from it, so this summary is based on that as well as watching the presentation.  While their name is 10X, the company emphasized progress on three axes: scale, resolution and access and that progress across the three different platforms. 

Tuesday, February 09, 2021

Could I See Myself at J.P. Morgan?

There's a question that others pop my way pretty much every year around J.P. Morgan: would I ever attend myself?  I'll confess it never occurred to me before I was asked, but that isn't necessarily a deal breaker.  I foolishly didn't attend AGBT until 2013 when Alexis Borisy (then CEO of Warp Drive) suggested I go -- I think it was mostly because he thought it was a good investment and probably only secondarily to keep me off the ski slopes for a week -- I shattered my knee just after AGBT 2012 ended.  It's an interesting but complex question which I will answer one way here, but freely admit that over coffee I could be nudged one way or the other.

Monday, February 08, 2021

Why I Hated One Genapsys Slide

I claimed in my Miscellanea piece that I was one post away from being done with J.P. Morgan -- oops, forgot I had drafted a minor screed on data display which I'll push out before the last piece - particularly since I hinted I would be taking Genapsys to task on this subject.  Unexpectedly good timing too: maybe new Genapsys CEO Jason Myer's first big initiative can be to fix this plot!

Saturday, February 06, 2021

J.P. Morgan: Miscellania

Before J.P. Morgan is truly a month ago I should clean up some loose ends as a penultimate post driven by this year's virtual conference (the last post isn't exactly time sensitive).  In contrast to the single company focused items that preceded it, this is a grab bag of minor observations and notes.

Thursday, January 28, 2021

J.P.Morgan: NanoString

Almost done with my J.P. Morgan summaries -- this will be the last focused on a specific company: nanoString.   They wish to emphasize that they are becoming the company for spatial analysis of DNA, RNA and proteins in biological samples.  They also want us to differentiate that space into two segments: profiling and imaging.  Profiling gathers spatial information from regions of multiple cells; imaging in their lingo covers spatial techniques with single cell or subcellular localization. In both cases nanoString is betting heavily on oligo-tagged antibodies to enable deep multiplexing of protein detection to be integrated with RNA and DNA detection.  

Monday, January 25, 2021

J.P. Morgan: Genapsys

Genapsys' J.P. Morgan presentation by CEO Hesaam Esfandyarpour focused on their story of delivering a compact sequencer based on electronic detection that offers low capital, low cost sequencing.  There were two bits of specific product news, but mostly general painting of a rosy picture.  

Tuesday, January 19, 2021

J.P. Morgan: PacBio

PacBio CEO Christian Henry’s presentation at J.P. Morgan wasn't rich in technical specifics. But he gave a very bullish portrait of a company aiming for the stars.  A conflict reminder: he’s a member of the Board of the Strain Factory that employs me, though I haven’t yet had the pleasure of meeting him.

The biggest news is a broad partnership with Invitae four clinical human genome sequencing. The only specific here is that this is not the whole enchilada; platform development will take place both within the Invitae collaboration and outside it. What might that development be?

Between Henry’s comments in the Q&A and a few info crumbs on slides there will be pushed to further tune all the canister. Her mentioned efforts on dyes and further improving SMRTcell loading efficiency. There was chatter on Twitter about an overdue update to improve HiFi yields.

Henry talked of the importance of increasing ZMW packing, but gave no specifics other than to suggest this is more "development" than "innovation" -- this was in response to a question asking if technical breakthroughs are required.   But we are left wondering on a timetable as well as what the next density might be; four-fold to 32M  wouldn’t be surprising on na├»ve geometry grounds. 

I suspect a huge area of joint effort with Invitae will be to automate HiFi library production. The current protocol is long, manual and labor intensive - not at all appealing for lease scale clinical use. How much of that will be retained as proprietary to Invitae will remain to be seen.  Henry claims that the Invitae effort will be separate but coordinated with existing development efforts; prior plans have not been shelved or diverted to support Invitae. A major software effort to support clinical operations is a given. PacBio has separate workflows for SNP and SV calling and those must be integrated and a clinician-friendly report generated. 

Henry believes that the new Sequel IIe will be the dominant product shipped going forward.  It will be interesting to see which of the older workflows PacBio updates and moves into the on-board compute.  For example, if you want to call methylation you must export BAM files with kinetics data, which are predicted to be five-fold fatter.  If the methylation calling happened on board, then that extra processing and extra data would be eliminated.  

Similarly, workflows such as microbial assembly are still based around Continuous Long Reads (CLR).  Henry didn't mention CLR once (I think).  While I doubt they would ever dump it altogether like they did Strobe Reads, it would seem likely that it won't get much attention.  Oxford Nanopore can beat them on very long reads and their single molecule accuracy is much higher; far better to focus on the CCS/HiFi reads where PacBio can deliver much higher accuracy.  It will be interesting to see if PacBio pushes the HiFi fragment read length longer.  On the one hand it will be more challenging to work with longer fragments and to routinely get enough circuits around them to deliver HiFi quality data.  Twenty five kilobases is a nice size for many applications, but there will always be incremental value for going to thirty or forty or beyond.

In response to a question about $1000 genomes, Henry described it as "just a number" around "where it makes sense" in high throughput applications.  He says the Invitae collaboration will be able to drive prices below $1000.  But he also pushed the idea that a PacBio genome is a truly clinical grade genome and has higher value than genomes produced on other platforms.  He argued that this higher value, in terms of higher diagnostic yield for rare diseases, will be more attractive to payers and that there will be a net benefit to the healthcare industry by ending diagnostic odysseys sooner.   He vowed to continue generating "diagnostic proof statements" to provide evidence to support the higher value claim.

Should be interesting to watch, particularly if you have a front row seat in front of a Sequel IIe,

Saturday, January 16, 2021

J.P. Morgan: 10X Genomics

As I attempt to collate various incomplete thoughts about the J.P. Morgan presentations I have read and listened to from genomics instrument shops, one thing stands out about 10X Genomics: they actually announced new gadgets and kits! I should thank the company for supplying the slides after I snarked on Twitter about how they weren't archived in the J.P. Morgan webcast -- but now it is there.  So either my eyes failed again or I had a personal IT failure (I think the website doesn't like iOS and I may have forgotten that).  The slides were presented by CEO Serge Saxonov

Thursday, January 14, 2021

JP Morgan: Illumina

Illumina presented at J.P. Morgan on Monday, reminding us that they aren't just a sequencing instrument company but an interlocking set of businesses focused on genomics. CEO Francis deSouza spent much of his time discussing the Grail acquisition and some of the other ways in which Illumina is pushing rapidly to become an essential part of clinical medicine, but there was one slide on future improvements to sequencing technology and a few on the lineup of existing sequencers.  Reminder: I'm working off public sources, as during the day we work closely with Illumina and they even sunk some serious cash into my employer last May.

Monday, January 11, 2021

J.P. Morgan 2021

The J.P. Morgan Healthcare Conference has started this morning in virtual form, so I'd really better get this draft cleaned up and out (indeed, Roche is presenting as I hurriedly type, though about pharma not diagnostics).  2021 already feels like a darker continuation of 2020, between the appalling putsch attempt in my nation's center of government last Wednesday and the still buggy roll-out of the coronavirus vaccine.  As I noted in my piece on the Oxford Nanopore Community Meeting, the many disruptions of 2020 make grading the progress of companies essentially impossible: many were disrupted by lockdowns, supply chain issues and the general distraction from the year of doomscrolling. 

Sunday, January 03, 2021

Advent of Code vs. FizzBuzz

A bunch of coding types at the Strain Factory participated in The Advent of Code, a clever 24-day set of programming challenges that runs each year before Christmas.  Each day a new two=part programming challenge was posted.  Technically it is a speed contest, but you won't find me on the public leaderboard as I'm not nearly quick enough to ever rate a point there.  One of my  major official activities last month was contributing towards screening candidates for three different computational positions, one of which we threw open to general data science experience.  As a result, I've been thinking far too much about the FizzBuzz problem and my prejudices towards it.

Saturday, January 02, 2021

Peri-New Year Nanopore Playing

Ever since the community meeting I've been toying with an idea,  then never quite trying to code it.
 So on New Year's Eve I started getting the dataset together and reducing it to a bunch of dataframes, and today I pushed that a bit further and started graphing some of it.  It's very much a rough project -- some of the dataframes have some issues I'm still chasing down with redundant data not being initially collapsed, but I think the data is accurate.  I also think I have my conventions consistent -- at one point confused myself into inverting the labels on the plots!  In other words, ApG would be labeled GpA -- not good! There's already some intriguing patterns, which are presumably the sort of signal tools like Medaka use to polish assemblies from FASTQ data aligned to draft references.