Mission Bio Launches Tapestri Single Cell Platform

The fact that tumors and their immediate environment is genetically heterogeneous has long been known, but tools for high-throughput assessment of this heterogeneity have only recently become available.  The whole field of single cell RNA-Seq has seen spectacular growth, as new methods enable greater and greater numbers of cells to be profiled from a sample.  Profiling the DNA content on an individual cell basis has not been quite as much in the spotlight, but now a start-up called Mission Bio is launching a microfluidic library prep workflow, Tapestri, to enable amplicon panels to be run in single cell mode.

iGenomX Riptide Kits Promise a Sea of Data

A theme for me in my six years on Starbase has been addressing the challenge of cost-effectively sequencing many small genomes.  While sequence generation bulk prices have plummeted, all-in library construction cost has tended to stubbornly resist dramatic change.  Large genome projects don't face quite such a pinch, but if you want to sequence thousands of bacteria, viruses or molecular biology constructs, paying many-fold more for getting a sequence into the box than you're paying to move it through the box ends up being a roadblock. Illumina's Nextera approach dropped prices a bit, but not really a sea change.  Various published protocols drop  costs further via reagent dilution, but these can suffer from variable library yield and an increased dependence on precise input DNA quantitation and balancing.  Even then, the supplied barcoding reagents for Nextera handle at most 384 samples, and that is only a relatively recent expansion from 96. I previously profiled seqWell's plexWell kits, which like Nextera use a transposase scheme but with modifications to enhance tolerance to input sample concentration variation.  plexWell also enables very high numbers of libraries, which better mates projects with large numbers of small genomes to sequencers with enormous data generation capabilities.  Now comes another entrant in the mass Illumina library generation space: iGenomX, which has reformatted their chemistry from a microdroplet mode intended for linked read generation to a 96-well plate format requiring no unusual hardware.

PacBio's Frankenpatent on Error Correction

Well, here we go again.  Pacific Biosciences launched yet another patent lawsuit towards Oxford Nanopore at the end of September, and already the hounds are baying for me to look at the patents -- which I've foolishly established a reputation of doing. I will remind readers that, to use a construction that exasperates my son, I have no memory of these topics being covered during the time I was in law school. (said construction also works for divinity school, seminary, yeshiva, dental school, military academy, etc). 

Dispatches from CDC AMD Day 2017

I had the singular honor and pleasure of speaking this past Monday at the Center for Disease Control and Prevention's Advanced Molecular Detection(AMD) program's annual confab in Atlanta.  Just visiting the CDC campus was already a bit magical -- along with the Kennedy Space Center and Cold Spring Harbor it's one of mythical places of human exploration to me.  But to actually stand at the podium? Wow!

I've collected below a bunch of separate mental threads, many of which probably should be expanded out to a full post in the future.

Why Is LISP So Rare in Bioinformatics?

LISP is one of the oldest computer languages and perhaps one of the most influential of the early ones.  Some of the other well-known Eisenhower era languages -- Fortran, COBOL and ALGOL, have certainly left their mark, but LISP and derivatives such as Scheme or Common LISP certainly carries more cachet among "serious" programmers.  COBOL has always been a bit of an easy joke and Fortran tends to mark you as old-school; use of APL (once a language of mine) would mark you as dangerously reactionary.  ALGOL begat Pascal and Modula II and clearly had impact on the C syntax family of languages (including bioinformatics mainstays Python, Perl and Java) As I'll detail below, learning LISP has embarrassingly ended up stuck seemingly permanently on my future plans queue.  But that's also because life never forced the issue:  while LISP has certainly been used in bioinformatics (as covered in a review from 2016 ) , its mindshare in the community would seem to be very minimal.

Teaching Biology Evidence: Old or New?

I've been toying over a week with writing something based on an interesting Twitter discussion started by Dr. Laura Williams (@MicroWavesSci) of Providence College pondering the best way to approach teaching molecular genetics (really, science in general) at the undergraduate level.  In particular, Professor Williams wondered about the dangers of branding various key experiments with the names of the experimenters, such as Hershey-Chase or Meselson-Stahl.  The risk she points out is that this can devolve into an exercise in memorizing names and dates without assimilating concepts, or conversely that some students will find the names more of a hindrance than a help.  I'm going to play a bit with this, but I do emphasize that for her this is reality and for me it is a hobby (or perhaps a retirement fantasy, if I should ever actually retire).  Or in other words, for the academic this is her industry but for this industrial scientist it is academic.

The Curse of Spammotation Lives!

High throughput sequencing of genomes is over twenty years old, which demanded the development of automated pipelines for annotating this data.  I've worked on such pipelines since the early 1990s, implementing them as a student and at two different corporate stops.  Indeed, we were reviewing results from my pipeline versus some of the other ones out there to see what can be done better.  And unfortunately, I've found infuriating problems with RefSeq entries annotated with NCBI's bacterial genome annotation pipeline.  Now I'm usually one to sing the praises of NCBI -- they are a key resource for biological research and they make available multiple spectacular public services freely to the entire world.  But I'm afraid this time I need to vent.

DNA vs. the Machine

Last week's news contained a story sure to raise eyebrows.  A group of computer security researchers from the University of Washington claimed to have demonstrated that they could hijack a computer via sequencing a carefully-constructed DNA fragment.  Visions of NextSeqs rampaging through the streets immediately sprung to mind.  The paper is interesting and has some useful warnings for the bioinformatics community, but certainly the news coverage has been strong on hype and alarmism.

Computational Biology & Math: Am I Just Faking It?

Over on Quora a common type of question is "Can I be a computational biologist if I am now an X".  Personally I take a very broad view and think just about anyone with intellectual curiosity can become any kind of scientist.  A related type of question is "how skilled do I need to be in Y to succeed in computational biology", where Y is most often programming, biology or math.  I got thinking about this and started wondering whether I am actually at all skilled in math.  Here is the results of that analysis.

A Third GridION X5 Pricing Plan

When Oxford Nanopore announced their GridION X5 instrument in March, I and others attempted to parse the difference between the two pricing plans  -- and I made a bit of a hash of it.  The X5 runs 5 MinION flowcells independently in parallel from a single desktop instrument, which also includes FPGA-based acceleration of basecalling plus a license to perform sequencing-for-hire.  Indeed, Matt Loose tweeted out an image of an "X6" and then mention of an "X7"; the X6 had a MinION plugged into the USB port and apparently the FPGA unit can keep up with seven flowcells all running simultaneously.  Now Oxford has launched an interesting third "Starter Pack" plan that offers an even lower price point for the system.

STAT Proves Not Resistant To Antibiotic Tropes

Tuesday's Boston Globe carried a piece originating from STAT news on an interesting natural product antibiotic, pleuromutilin.  A research group recently published a new total synthesis of this fungal terpene, an advance which promises to enable greater medicinal chemistry around the molecule.  That part is cool.  Unfortunately, when it gets to the biology of pleuromutilin the piece by Eric Boodman completely spits the bit, trotting out some horribly inaccurate tropes.

New Life in the Sanger Market

In my bit on "I'm not dead yet" technologies recently, I included large scale Sanger sequencing. That reflects to a large degree my personal experiences and biases.  Targeted Sanger is great for spot checking the occasional junction or misbehaving clone or strain, but I forget that many clinicians still see it as a gold standard.  Apparently there are others who disagree with me, as Thermo Fisher recently launched a new Sanger instrument targeted at small labs, and according to GenomeWeb Promega plans an instrument offering in the same space as well.

Ice Ghosts:A Shortage of Maps

I'm going to step outside the usual topic space here and cover an interesting but frustrating book I read partly on the flight to London Calling (which is about the only connection it has to genomics).  Ice Ghosts, by Paul Watson, covers the searches for the lost Franklin Expedition, a mid-1800s British Navy attempt to find the Northwest Passage.  It's a pretty good book, after all it did win a Pulitzer Prize,  The topic is thrilling: explorers under difficult conditions and a mystery that lasted over a century.  There are lessons for science in general, such as the value in carefully evaluating oral histories that some would discard as unreliable. But what is maddening for me is that in a book for which a central theme is poorly understood geographies and their interpretations, the set of supplied maps fail miserably at assisting in the telling of the story.

What Is (and Is Not) Sequence Assembly?

In the closing talk of the pre-London Calling workshop, Hans Jansen had closed his presentation with a question whether at some future date sequence assembly would become obsolete.  This was meant to be an aspirational vision for a distance timepoint, but one correspondent on Twitter saw it as hype.  I got in a bit of a discussion, constrained by the dreaded 140 character limit, which ended up largely illustrating that I have a somewhat more restricted definition of assembly than some people.  I'm going to explore this and you can judge for yourself

London Calling 2017: Plant & Animal de novo Genomes

Okay, I'm desperately behind on writing up the external science from London Calling.  Not helpful that I claimed I would not only do so, but in multiple installments.  A number of the plenaries focused on large genome assembly, so that's what I'll tackle now -- plus a few other bits.   See also my Storify summaries, which include other reports on the conference.  Also check out my storifies on the SMRT Leiden conference, which ran at the beginning of the same week and discusses many similar topics.

SFAF & I'm Not Dead Yet Technologies

Jonathan Jacobs posted his annual reminder that the Sequencing, Finishing and Analysis in the Future Meeting (SFAF) will be this week.  Alas, that meeting hasn't had many more tweeters in the past than Jonathan, but perhaps this year there will be more.  There's a glut of genomics conferences to track, compile tweets and opine on -- besides London Calling, there's been SMRT Leiden and Biology of Genomes, all in the span of two weeks!  This post is going to be a bit short on actual writing and more to just flag some talks at SFAF that grabbed my attention.  What I realized is that the talks at SFAF illustrate that a number of technologies I consider effectively dead retain significant attention.

#ImBiased, but… Best conf. of 2017: #SFAF2017 #infectiousdisease #inherited #disease #agrigenomics #human #genomics https://t.co/yTu2MxKc41 pic.twitter.com/FCoSmTp6an

— Jonathan Jacobs (@bioinformer) May 10, 2017

London Calling 2017: A Theme of Consolidation

London Calling 2017 came to a close last Friday.  Any excuses of jet lag or nights running up ONT's bar tab won't hold up much longer, so time to finish this post (I really did start the night after Clive's talk!) I'm going to largely divide coverage on the dividing line of who presented: today's piece on Oxford Nanopore presentations, particularly Clive Brown's, and in the near future at least one focusing on the science users presented.  For other summaries of the action, I've created a storify of just blog posts and similar summaries of the meeting, as there were a great number (and I am on the hunt for additional ones I've missed)

Nanopore Workshop Notes

I attended on Wednesday the London Calling pre-conference workshop, an add-on for those wishing for help getting started with MinION sequencing.  Judging from who I spoke to, many participants were utterly new to nanopore sequencing and more than a few were like me in that they had tried the platform and wanted to do better.  My colleague has gotten some very good results recently, which has re-fired my determination to get good at that myself.  Below are some limited notes I took that may be of general interest. Large portions of the workshop will go largely uncovered, as I focused on what was surprising or new.

London Calling 2017: A Preview

Oxford Nanopore's London Calling confab runs Thursday and Friday, with a training workshop on Wednesday.  I'll be there -- who can resist a conference nearly at the Tower of London? -- and will also be testing whether my personal "field of nanopore sequencing suppression" can defeat ONT's best trainers.  Here's some preview of what I'll be particularly looking for, though being surprised will be lots of fun too. Much more fun that reading (the wrong) patents!

Oxford Nanopore's Enigmatic Patent Litigation

Oxford Nanopore has launched lawsuits in the UK and Germany against Pacific Biosciences, alleging infringement of a European patent licensed from Daniel Branton's lab at Harvard, EP1192453, which is apparently exclusively licensed to Oxford.  When I wrote about Pacific Biosciences first lawsuit against Oxford Nanopore late last year I titled it "PacBio's Quixotic Patent Litigation", as it appeared the Oxford could easily dodge the lawsuit by abandoning the 2D sequencing technology, which Oxford is in the process of doing.  I've swapped in "enigmatic" for this title, as I'm not even sure what aspect of PacBio is allegedly infringing the patent.