Omics! Omics!

ASHG Notes: Myra Liquid Handler

2026-11-09T10:03:32.167-05:00

After some detours into other areas, I'm back to writing up my ASHG notes from a few weeks ago. I've encountered the Myra liquid handler at meetings going back to last year's ESHG in Milan, and have considered writing it up each time. That cycle has been made more painful because I've declared to their local rep, whom I've known for a while, that this time I'd write it up. Finally this is "this time"!Read more »

Autonomous Labs Create New Instrument Niches to Fill

2026-11-04T23:08:39.483-05:00

When I give tours of our Nebula autonomous lab installation, one thing I like to note are instruments we have integrated that are workhorses for us yet still could be a bit better. A running theme here is that most laboratory instruments were developed for walk-up use by individual scientists, with some automation integration capabilities grafted on to enable workcell use. Or they were designed for workcells. In either case, issues for autonomous operation arise such as being far too batch oriented, rather than asynchronous experimentation, as well as requiring skilled manual servicing. Creating new instruments for an autonomous laboratory world is a great open innovation opportunity for academics, startups, and other mechanically-minded persons. Today I'll talk about reagent filling.Read more »

Can AI Decode Glycolysis Enzymes By Their Moonlight?

2026-11-03T22:58:52.698-05:00

Serendipity can be amazing. At a great lunch recently with Jake Wintermute, Patrick Boyle, and Ash Jogalekar we were roving around AI topics and synthetic biology with great relish (though my burger did not bear that condiment), and I threw out an idea I've had that riffs of a Jef Boeke paper I'm completely derelict in covering here. I was thinking of scribbling it up, and then via a Quora request I came across a fun review that was directly relevant to my specific idea - which I'm now going to expand into a completely technically feasible, scientifically interesting, and insanely expensive grand exploration. What I propose to do is to try to rewrite one of the most fundamental and universal biochemical processes, glycolysis, every way I can think of in as many places as possible, and in doing so uncover unknown foundational rules of biology.Read more »

Protein Engineering in Middle & High Schools?

2026-11-01T23:00:43.126-05:00

New tools in the protein design space seem to drop nearly daily now, and many of these are free to all, open source, or at least free for non-commercial use. Since I'm in the cloud lab business, and we have workflows built or all but built that can support many protein engineers, I'm very curious about to whom I might market such services. Given the ease of running these tools, will we see students at levels much below college start taking on protein engineering as part of the curriculum or as special projects?Read more »

The Cache

2026-10-31T20:31:16.363-04:00

If the lunar prospecting startups hadn't been scanning the moon at ever greater resolution, perhaps it would have never been found on the far side, but nothing that shiny was going to go undetected. Multiple companies found it around the same time, and while they tried to stay quiet the news soon leaked out. A hastily assembled robotic mission succeeded in capturing high resolution images, which made it clear this was no natural meteor. The lack of an impact crater would have been astonishing, but here was a metallic object that had clearly been crafted.

Two Decades!

2026-10-28T21:15:14.453-04:00

Today marks two decades since I started writing here. It is not a coincidence that it is also twenty years since I was officially notified by Millennium Pharmaceuticals that my services would soon be no longer needed. Millennium had a strict no social media policy. When rumors of major layoffs swirled, and especially when I was tipped off a few days early that I and nearly my entire department were getting the axe, I primed myself. Of course, that meant twenty years ago I committed a severe breach of that social media policy, but I thought at the time I had only two weeks at risk. Sure, they could have clipped my exit package, which was relatively generous, but I think management wasn't too worried as long as I didn't go causing trouble, as they were busy radically restructuring the company.Read more »

ASHG Notebook: Chatting with Alex Hoischen

2026-10-28T09:21:19.932-04:00

I caught up with the eminently quotable Alexander Hoischen at ASHG. After we spoke for about 15 minutes, I realized I should have been taking notes - and Hoischen was generous enough to go back through some key points with my pen scribbling. He can also be counted on for some gastronomy - in this case some pastries he had purchased at a French bakery elsewhere in Montreal.

ASHG Notebook: seqWell's ONT Library Prep

2026-10-27T09:57:32.095-04:00

seqWell CSO Joe Mellor gave me a quick tour of their new transposase library prep product for Oxford Nanopore sequencers. Since the early days of ONT, users have had two basic choices for genome library prep: rapid method relying on transposase or the ligation kits. Rapid is so stupid simple even I can do it (just don't ask for my yields!); ligation requires more molecular biology skill due to multiple enzyme steps as well as bead cleanups. Ligation had higher yields than rapid - so simple but lower yield rapid or much more complicated but higher yield ligation? seqWell's approach is only slightly more complex than the rapid kit, offers a large number of barcodes, and has flowcell yields on par with ligation.

ASHG Notebook: Bruker PaintScape Illustrates Chromosome Architecture

2026-10-26T22:17:24.468-04:00

I spent last week at ASHG in beautiful Montreal. I've scribbled many notes in my notebook, and am planning to emit a series of pieces each focused on a single topic. Some of these may be brief, but I hope still interesting. Far too many of these cover topics I had similar notes on from AGBT that never made it into pieces - such as the following on Bruker's PaintScape instrument.Read more »

What Instrument Protocol Did I Actually Use?

2026-09-28T23:05:44.423-04:00

Puttering around with some ideas for future experiments on our autonomous lab, I realized a potential software engineering gap that in my very hot take is ubiquitous in the industry. For complex instruments such as thermocyclers, plate readers, imagers and many others, a run involves triggering a specified protocol. These protocols are often saved on the instrument under a name, enabling a protocol to be called by name. But what are you actually running? If I'm correct that my new worry is a valid one, it will be something every effort to standardize access to instruments - such as PyLabRobot and the proposed Model Hardware Standard - Read more »

What About BOB-Seq?

2026-09-26T23:25:50.701-04:00

An interesting new approach to short read RNA-Seq library preparation bobbed into view this week, using click chemistry to barcode samples before any enzymatic processing. This bioorthogonal barcode sequencing approach - aka BOB-Seq - offers great promise in the burgeoning space of perturbing cell lines with drugs or other agents and then profiling the RNA. Read more »

Sequence That Moldy Lanternfly!

2026-09-20T23:27:47.264-04:00

Googling on some keywords from a social media post led to an interesting PNAS article from 2019 on two fungi which can infect the spotted lanternfly. Lanternflies are a species accidentally imported from Asia which have been striking fear into many plant lovers in the Northeastern US. If they'd just stick to tree-of-heaven, an imported plant that grows well in the US but accrues little to any love, but instead they suck sap from a wide variety of trees and vines, with particular love for grapevines, many orchard trees. and maples - among others. They have still been spreading alarmingly up the I-95 corridor - often hitching rides as egg masses on the undersides of cars. Biological control methods are of great interest - birds and toads apparently will consume lanternflies but equilibrium hasn't been reached. The PNAS paper, written by researchers from Cornell University, looked at two native fungi which can attack lanternflies. What surprised me on further searching is that one of these fungal species has no genome assembly at NCBI!!!! Read more »

Does Your Instrument Strand Its Data in an Proprietary Binary Format?

2026-09-18T12:33:27.458-04:00

This week we hosted the first REAL (Readiness & Engagement For Automated Labs) Summit; today that was followed by Ginkgo Datapoints Summit. Both were fascinating surveys of the leading edge of automated data generation and feeding that data into AI models. That data generation relies on linking sample preparation instruments to data generation instruments. Two of my recent pieces were around issues of interfacing with instruments: Anthropic's proposed but not disclosed Model Hardware Standard and some of my (perhaps painfully naive) stabs at evaluating instrument Application Programming Interfaces (APIs). I had commented that some instruments lack APIs - but what if even worse the data is still locked into a proprietary format?Read more »

A Marvelous Demonstration of This Proposition Which This Context Window is Too Narrow To Contain

2026-09-16T11:09:19.080-04:00

My friend and former colleague Ash Jogalekar tweeted out an interesting result recently, which is now expanded into a preprint. Using an intelligent agent, he had generated a mathematical proof and then applied it to an interesting problem in nucleic acid structure design. Ash also freely confessed that he lacked the mathematical background to evaluate the proof himself, which means it is utterly hopeless for me to dream of comprehending the proof since he has far more mathematics understanding than I do. That touched a very sore spot in current mathematical academic discourse: how to deal with AI-generated proofsRead more »

Notes On Instrument APIs Critiques I Delegated to Claude

2026-09-03T10:41:22.883-04:00

In my previous post about the Model Hardware Standard from Anthropic, I mentioned some exploration I've been running on instrument APIs. Given our Catalyst Agent skills, a model such as Claude can evaluate what gaps exist between a given API and what we would require to integrate into our RAC autonomous laboratory environment. I've run only a few APIs through, and I'm not going to reference which ones, but I have seen some patterns. The whole process has been very thought-provoking.Read more »

Model Hardware Standard: What Is It? Seriously, That's What I'm Asking.

2026-08-31T23:26:27.548-04:00

Anthropic, the company behind Claude, announced a new initiative called the Model Hardware Standard (MHS). It's a way to enable intelligent agents to talk to laboratory instrumentation - well, that's what it's billed as. But as first surfaced in a tweet by Sina Booeshaghi, if they want to be a standard they're taking a counterproductive path to it, as the announcement was only that. A blogpost extolling the goals of MHS is given accompanied by testimonials from two early access sites , but no open and substantive description of MHS itself that would allow evaluating what it can and cannot do. Read more »

Recombination-Based Autonomous Protein Structure-Function Search

2026-08-27T09:55:34.112-04:00

An interesting preprint showed up last week in the autonomous agent-driven experimentation space - an area I'm paid to be very interested in. This didn't run on our hardware, but we certainly could reproduce the experiment on our autonomous laboratory installation Nebula if the preprint had all the critical details (I'll try not to kvetch constantly about that, but it is an annoying brake on my eagerness to reproduce some or all the results). Anyone could run it on our Cloud Lab - I haven't priced it out but this should come in at a very reasonable number. What I found particularly clever is the solution to the problem of keeping protein engineering by AI in a reasonable cost envelope - and this is accomplished by relying on chimeras which can be a generated from one round of DNA synthesis and then clever shuffling.

Learning protein function through autonomous experimental interaction

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https://www.biorxiv.org/content/10.64898/2026.08.14.744985v1
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SIMB Notebook: The Frontiers of Protein Engineering

2026-08-20T21:51:41.067-04:00

The Society for Industrial Microbiology (SIMB) annual meeting in Austin the first week of the month was great fun. I caught up with two Warpers, saw some other contacts from that era and met a bunch of new friends. Plus I showed the flag for autonomous laboratories with a talk in a session on applying AI to the field - and got a chance to talk to multiple users of our systems at customer sites. Murphy's law struck in that our PR on four academic placements of autonomous labs came out about 20 hours after my talk. In addition to the session I appeared in, I attended a keynote on protein engineering, a session on enzyme engineering, and a whole day of talks on natural product research - plus all the posters. I have a few notes that are maddeningly incomplete & I apologize in advance for the quality of attributions. But here are a few observations on the space on protein engineering, which I am trying to level up to "barely dilettante" grade.Read more »

HiFi's Not Very Pacific Waters

2026-08-18T23:40:33.114-04:00

PacBio had a major shakeup early this month. First came a large round of layoffs, which caught several individuals who were very much the face of innovation on social media. Next came the sudden retirement of CEO Christian Henry, who has appeared in this space multiple times, and the elevation of CFO Mark Van Oene to the top seat.

When PCR Gives You Lemons...

2026-08-03T00:07:05.434-04:00

I wish to highlight an interesting new preprint from a group at Danish Technical University which explores the schmutz in PCR reactions, demonstrates some surprising conclusions, shows how their results might be very relevant to a common use of amplicon sequencing, and demonstrate a specific utility running PCR on in cases where typical PCR absolutely can't succeed. Put another way, how often do people patent what was previously considered uninteresting experimental artifacts?

Dad Had Manuals, I Have An Agent

2026-07-28T14:29:13.933-04:00

My father was a very methodical person, and that particularly applied when he decided to purchase the second IBM PC clone to appear on the market. A whole host of manuals appeared on his desk and when I started skimming them it was clear he had been there first. Sentences highlighted, marginal notes and of course editing marks to suit his sense of grammar and style. The hardware, operating system, and APL programming language by far represented the most complex technology in the house - easily more complicated than everything else put together.Read more »

Element's Curious Patentsieg

2026-07-21T22:02:50.860-04:00

Last week news broke that Element Biosciences had won a patent lawsuit against Illumina, and that it affected MiSeq. MiSeq???? How did a patent battle in 2026 affect a platform launched nearly a decade and a half ago? And which had been launched about five years before Element incorporated. Which is being put out to pasture, though the MiSeqDx version What witchcraft is this? I've done limited digging - I really dislike trying to dig through patents - and it is a strange case.Read more »

Fiber-Seq: Plasmids Model Chromosomes Well

2026-07-20T10:54:22.618-04:00

A recent publication in Molecular Cell involving Fiber-Seq caught my attention, though I've since discovered this preprinted over a year ago. One of the challenges in exploring the effects of genetic variations is the cost & effort to generate collections of variation which can be profiled by available methods. This paper explores using Fiber-Seq on transfected plasmids and finds that, with important caveats, transfected plasmids evoke the same patterns of chromatin protection as the corresponding nuclear DNA. This opens up the possibility of exploring large sets of variants for their effect on chromatin structure and either feeding that data into models or using it to understand clinical non-coding variation. Or why not both?Read more »

The Simulator That Isn't There

2026-07-10T09:14:08.954-04:00

Okay, this is one of those cases where I kvetch about other people not having built the tools I want to use - perhaps a bit of a insufferably egotistical position. I mean, what gives me the chutzpah to do that? My title, according to me, is "Automation Visioneer", so that gives me the right - though again, self-given title, self-given right. But I hope you'll bear with me, because I think (there again, me! me! me!) it is an interesting observation on a curious gap in the software world - one that could make a very interesting project for someone so inclined. Oh, and this is one of the "a bit of promoting the product" entries - which means I get to blog on company time.Read more »

Countable Labs Raises Funds, Heads to Clinic

2026-07-07T11:44:18.444-04:00

I caught up by teleconference recently with Countable Labs CEO Giovanna Prout, fresh off Countable Labs' $26M equity fundraising - a round which was oversubscribed. Top on my agenda: what is Prout's vision to turn that money into products. And how will Countable balance building molecular tools vs. applying those tools to clinical problems?