Shredding Genomes: Establishing Plausible Deletability

There's an interesting new preprint from Jay Shendure's lab which introduces the technique of Shred-Seq, which is a Cas3-driven approach to generating large deletions across a large eukaryotic genome.  By creating diverse collections of deletions, Shred-Seq enables identifying hidden non-coding sequences of functional importance.

The Commercial End for Fluidigm Technology?

Last week brought news that Standard Biotools, which is what Fluidigm morphed into, is being acquired by Treeline Biosciences, a drug developer.  The deal values Standard at about its cash position - and Treeline made it immediately clear this is a reverse merger to grab the cash and in effect go public by also grabbing Standard's stock listing.  What Treeline has made very clear is that they have absolutely no interest in is Standard's existing tools portfolio.

Long Reads for Rare Diseases Hits New England Journal of Medicine

Alexander Hoischen and colleagues have a brief piece in New England Journal of Medicine that published early this morning, in conjunction with the European Society of Human Genomics (ESHG) meeting.  I'm now in the thrall of ESHG FOMO - I attended last year in part because it was immediately after London Calling and it seemed silly not to extend my trip (plus Alex had asked me personally to go), but this year I reluctantly decided my travel load was getting high and decided to make only one transatlantic flight in the May-June timeframe.  Hopefully I picked the right one.  The piece is the latest installment of a long running program to demonstrate that long read sequencing, specifically PacBio HiFi sequencing, can replace a battery of older tests when trying to diagnose rare genetic diseases.

Craig Venter Reflections: Building & Redesigning Genomes

The last bit of Craig Venter's career a followed, often a bit green with envy, was his work to build genomes.  This all revolved around the Mycoplasma genitalium they had knocked out a genome as a victory lap after completing the first bacterial genome.  This bug is held up as the bacterium with the smallest genome which can be grown in a defined medium.  To first reconstruct an entire genome, with watermarking sequences to prove it was done, required pushing every limit of the existing gene synthesis cloning technology.  An effort so intense, that collaborator Dan Gibson became a verb! (See that gene cluster we want?  We'll Gibson it into a BAC vector.")

Craig Venter Reflections: Human Genome

Few bombshells have hit genomics like the day in May 1998 when Craig Venter and Applied Biosystems announced he would be launching Celera Genomics to sequence the human genome by a complete shotgun approach.  A couple of colleagues at Millennium had just announced they were leaving to form a contract research organization which would perform high throughput sequencing on demand - they were certainly rocked back on their heels (though not blown over; Orion Genomics remains successful to this day with a focus on palm oil genomes).  The public project was also rattled - Celera was promising to deliver a private genome much sooner.  In some ways, it was the EST brouhaha all over again - except with important twists.

Craig Venter Reflections: Small Genomes

In the early 1990s, Craig Venter left the NIH over disputes around the patenting of ESTs.  Investors backed him, but then William Haseltine basically pushed him out of direct operation of Human Genome Sciences (HGS) and Venter went to start The Institute for Genome Research, far better known as TIGR.  TIGR would attract an amazing array of talent both wet lab and dry lab - a pattern that Venter had established.  I believe it was around then that Venter attracted both Clyde Hutchinson and Hamilton Smith to TIGR - two giants of microbiology (Smith had a Nobel Prize!), and they would collaborate with him for the rest of their lives.  HGS would have human biology to themselves, but TIGR was free to explore other parts of life domain.  And it would be in the sequencing of microbes that Venter and TIGR would radically shake up a world that, as I reviewed in the previous piece, was debating how many levels of physical maps to build.

Craig Venter's Genomics Revolution: Setting the Stage

I am overdue in getting back to my very personal review of how the recently passed J. Craig Venter made a huge impact on genomics science.  But especially after being at London Calling, I worry that many in genomics today just won't have the context to grasp how unusual his approaches were.  I met some amazing graduate students there - and most likely they were born after the joint announcement by Venter and Francis Collins of the human genome initial completion.  So with the risk of writing a "back in my day we walked uphill to school both ways" piece, I wish to sketch a debate that the genomics world was having in the early days of the Human Genome Project.

FoG to Roll into Boston Seaport Wednesday & Thursday

The Festival of Genomics, Biodata and AI - thankfully known as FoG and not FogBA or FogBDA - will be at the Boston convention center this Wednesday and Thursday.  It's an interesting conference that typically has two editions each year, one in London and one here in Boston.  I'll be wandering around the floor part of both days - my beacon/hat to be announced on LinkedIn and Twitter that day (leaning hard towards my yellow University of Delaware hat).  FoG works hard to not be your average scientific conference, and I'd like to run down a few things I'm anticipating.   By the way, the world's largest autonomous lab is less than a mile from the conference site and tours are available during the conference - all you need to do is reach out to the tour coordinator to schedule one.  And I'm that, so DM me on LinkedIn and I can set you up.

London Calling: Long-Term R&D

Now to run through the long term technical projections from Oxford Nanopore's Tech Talk.  Well, projection is probably not the correct word - hints and teasers might be closer to the mark.  None of these pronouncements came with any hint of timing for when the community might be able to access them - indeed, CSO Lakmal Jayasinghe made it very clear that this section would have no timing information.  Here is a link to the presentation: what is covered in this piece starts around the 44:40 mark.

London Calling: ONT's Near Term Launches

I returned from London Calling 2026 much as I usually have - exhausted, more than a little hoarse, happy for discussions had and ruing connections missed.  The meeting felt much like prior ones, except in all the ways it was a little different.  The company continues its trajectory towards restraint and corporate maturity, with new CEO Francis Van Parys for the first time exhibiting his "evolution not revolution" messaging for the company's direction.  ONT's technical presentation was divided into two parts: near term that came with release dates = none of them even as distant as the end of the summer - and long term which had no hint of timing.  This piece will focus on the near term advancements and a separate one will cover the long term updates.  The entire presentation is already available on YouTube.

London Calling 2026 Preview

My series on Craig Venter is on a small pause since I didn't get it out before I arrived here in London for Oxford Nanopore's annual shindig at Old Billingsgate.  On the plus side (well, I hope my readers find it a plus), I've sketched out an additional piece - I realized that our world of fast whole genome sequencing powered by long read technologies such as Oxford Nanopore may make it challenging for many to remember the genomics world of the 1990s and how there were great differences in opinion on how to go about sequencing genomes.  But back to London Calling - this is an interesting moment in the history of the company and it shows in the program. So without more ado, here are some key topics and questions on my mind.

Personal Reflections on Craig Venter: Expressed Sequence Tags

Venter's big Expressed Sequence Tag - soon known as ESTs -  paper came out in June during my final summer as an intern; I photocopied it at my internship. I looked it up, and it had only a bit over 600 sequences - a small beginning to what would become an industry-wide exercise.  That was a momentous time for me, as only the past December had I pivoted from thinking I would get a degree in experimental plant molecular biology to focusing on computational genomics. Venter was not the first person to feed an RNA library into a DNA sequencing workflow without prior screening; I believe Gregor Sutcliffe holds that milestone.  But Venter did it on a much larger scale and with much more flash.  He pitched it as a way to skim the cream of the human genome when the official Human Genome Project was just getting going.  And as would characterize much of his career, it is the response of others in the community that was as much his contribution as his own work.

Personal Reflections on Craig Venter: Preface

Craig Venter's sudden passing has triggered many writings about his life and work.  I'm overdue on my own personal reflections, and am breaking them into three thematic pieces. While I only met him a few times and never one-on-one, his career had an enormous impact on mine. So I am going to write a series of posts this week reviewing, in a very personal way, Venter's enormous impact on genomics and synthetic biology. I'm sure I won't do it proper justice, and I won't be surprised if my memory plays tricks on me - please do point out any egregious errors of fact and feel free to contest my opinions if you feel they are unfounded.

If My Agent Can't See Your Catalog, Will It Exist Much Longer?

Another edition of my dabbling with AI.  Somewhat like what I reported before - a customer asked if Ginkgo Cloud Lab's Echo-MS option could configure an assay to replicate the analytical results in a published paper, so I'm using Claude to do the heavy lifting.  Plus part of what I described earlier showed some issues on review.  But the big thing I'm keying into this morning is Claude is having difficulty with accessing a major chemical catalog I pointed it at - and I wonder how long that situation will be tenable.  Maybe not for a big company, but how many small companies will have an existential crisis when it turns out AI co-scientists and full agentic scientists have been silently passing them by?

Crossing the Vibicon

Vibe coding - solving problems by extended conversation with a machine learning program rather than writing the code yourself - is all the rage.  But I hadn't really been partaking, finding one excuse after another.  I don't have time.  It's a lazy approach to the craft I've honed.  Abandonment of my skills.   But I've also taken to referring to myself as a "lapsed computational biologist", as I was never doing any coding - or looking at biological data.  I'm business development now, which is a bit of a euphemism for salesperson.  Still, a bit of a pang - and all of my colleagues were vibing away.  And then an old friend/colleague said they fed my recent column on LinkedIn to an AI and it generated code to replicate my little parser  - and this colleague has never programmed!  He sent me the code, which I've skimmed but not tested - looks about right.  And so confession time - I have drunk from the well of vibe coding and do not plan to stop drinking from it anytime soon

An artistic depiction of Julius Caesar's transgression, pulled from Wikimedia

Invivoscribe PrepQuant: Streamlining Clinical DNA Extraction

The liquid biopsy space continues to grow and heat up - just this week Roche's Foundation Medicine unit announced the acquisition of Minimal Residual Disease (MRD) test developer Saga Diagnostics for just over a half billion dollars.  Numerous MRD and Multi-Cancer Early Detection (MCED) companies continue to spring up, with even more analyte types - first it was cell-free DNA, but now cell-free RNA and exosomes have entered the picture and probably a bunch more.  Extracting DNA from biofluids - mostly plasma, but sometimes urine or something else - is a critical step with many available methods - and many of those are labor intensive or incompletely automated.  As testing volumes scale, there will be a need to reduce the hands-on effort both to keep costs down and consistency up.  Just before AACR, Invivoscribe unveiled a new instrument for cell-free DNA purification and quantification which intends to reduce hands on time significantly over existing methods.

AGBT Agriculture 2026: A Few Paragraphs on Graphs

AGBT Agriculture was a really nice meeting - lovely venue in the Arizona desert, a meeting size that you felt you could (but weren't compelled to) introduce yourself to everyone, good food, great scientific content, and everyone super-friendly.  I came for the workshops on Sunday, and there were two on graph genomes / pangenomes.  Which was a theme throughout the meeting - not every talk or paper mentioned these topics, but a huge fraction did.  The agriculture world - both plant and animal (hmmm, no mushroom talks that I can recall) - is completely sold on the utility of graph genomes.  Ideally really large ones not only capturing the complete genomic diversity of a species, but also layering in information from related species so that the graph can service questions of when particular genomic features arose in evolution.

Flowers: A Matter of Timing

I'm headed over to AGBT Agriculture tomorrow, after getting to Phoenix ahead of time to check out some sights.  The Desert Botanical Garden is amazing, particularly since it stays open until 10pm and so you can watch the lighting change as the sun sets and then enjoy some artistic artificial lighting on some of the trails.  Before I left, a few daffodils were in bloom back at my home.  So while I have plants on the mind, I'll unleash another plant engineering fantasy but this time with a dose of contemplation whether it would really be a good idea.  What if we could engineer flowers to show up at any time we wanted?

A Wish For Snail-Inspired Tulips

About a year ago we took a family vacation to the Netherlands with a prime goal to see tulips - and tulips we did see!  Even a rainy day (what are the odds of that in Holland?) couldn't steal the magic from the famed Keukenhof Gardens, and outside the renowned Rijksmuseum was a spectacular tulip bed.  I'm now dealing with one side effect of that trip - I went a bit overboard ordering bulbs on our return and because our garage is a bit warmer than outside I now have many pots of bulbs which are far ahead of the schedule set by those in the new garden beds I was ordering for.  Nice problem to have.  But as much as I can go crazy with existing varieties of tulips, I'd love to see even more varieties.  Indeed, I have some very specific ideas for engineering tulips that I would find irresistible.

One of several hundred shots I have of bulb beds at Keukenhof

Keukenhof ornamental windmill with a field of tulips in foreground, seen from the electric "whisper boat"

One of dozens of shots I have of the beds by the Rijksmuseum

icon16: Precise Amplification for All!

I've loved the n6tec icon96 instrument since they first tipped me about it several years back.  The idea of running 96 independent PCRs in parallel was just too attractive; the instrument I'd always dreamed of. I never take payments from companies I write about, but probably could make a reasonable claim on commissions for a few icon96 units - I have a hard time not going into total fanboy mode.  But not everybody works in batches that are multiples of 96 - and now at ABRF n6 has launched an affordable option, the $29.5K icon16, to enable nearly any lab to access this technology.