The Encyclopedia of DNA Elements https://www.biorxiv.org/content/10.64898/2026.07.06.731365v1

We are finally putting the final touches on an operationally complete mapping of regulatory DNA via DNase I in both human (>4,000 samples) and mouse. To interact with the samples we created this neat browser interface complete with a chatbot!

Check out ths CBS news segment about me. I may be the first person in world to be recieving a preventive ASO therapy for inherited familial ALS and it appears to be working! Still things to be hopeful for despite the absolute dumpster fires occurring all over the world. youtu.be/1BdZb67w43s

Exciting results! We developed a single, generalizable ML model that can predict chromatin accessibility across any arbitrary cell type using a sample intrinsic and portable embedding. Notably works on samples generated over a 15 yr time interval with different technologies & methodologies.

Surprised (but also not that surprised) that the AlphaGenome paper didn't officially cite any of the primary data used for training their model (see Fig. 1, thousands of datasets made with tremendous time and effort over >15yrs). What's up with that @nature.com ? www.nature.com/articles/s41...

Getting up-close and personal with the Patagonian fjords near the Beagle Channel.

SPrUCE: Utilizing Ultraconserved Elements of DNA for Population-Level Genetic Diversity Estimation https://www.biorxiv.org/content/10.1101/2025.11.14.688492v1

Double full rainbow at the end of the world at Cape Horn, Chile 🇨🇱

With all the wild stuff going on in the States (and the world) I am going to escape reality for a while on a sailing trip to the end of the world around Cape Horn and the Beagle Channel (named after the HMS Beagle of Charles Darwin and Robert Fitzroy fame). Thinking this might be type 2 fun...

🥁This Wednesday , in #FragileNucleosome seminar, we are excited to host @hannahlong.bsky.social and @jeffvierstra.bsky.social to tell us about amazing work they are doing! 🗓️Register here for upcoming session and the entire series: us06web.zoom.us/webinar/regi...

Southern fjords of Chile on a boat.

It’s been a pleasure to organize the Rules of Protein-DNA Recognition meeting in Cancun. Spectacular talks and an amazing and supportive scientific community!

Great resource! I should mention (since it's not on the website) that all of the chromatin accessibility data (DNase I) was generated at the UW & Altius Institute over the course >15years. The proper references for these data are: www.nature.com/articles/nat... and www.nature.com/articles/s41....

Please apply to our tenure-track faculty position at @stanford-chemh.bsky.social! We are searching for a new colleague working at the interface between computation and molecular sciences. See post below and pls forward widely! chemh.stanford.edu/opportunitie...

Looks like a great couple of months of seminars! Come check out my talk on November 5th if you want to learn about our progress in mapping the nucleotide-resolved structure and function of cis-regulatory DNA elements across thousands of cell types and states.

Wild to see a thread about me. I think the broader topic (as Jason points out) is what does the future of preventive medicines look like for at risk gene carriers? I also hope this gives people some hope to those dealing with devastating and (previously) unactionable inherited genetic diseases.

Does one sample (or even 10) suffice to define core cell type regulatory elements? NO! Because of both biological and technical variability you need to profile many (typically >15). The additional peaks are enriched for trait associated variants, so you miss a lot of possibly important signal.

Look at this and tell me I am wrong : DNaseI footprinting data is unparalleled in genomics. ~700 high quality datasets for an upcoming ENCODE data drop.

Activity determining nucleotides on the BCL11A +58 enhancer according to a ML model built purely on DNase I data from thousands of cell types (this is just prediction for erythroid cells). Not bad w.r.t. functional data. The GATA1 site is the therapeutic target of Casgevy for SCD and B-thal.

For some reason I was re-reading the DEseq2 paper and was reminded of what a statistical masterpiece that method is. Every time I read the paper I seem to learn something new. Not too many papers achieve that bar (at least for me).

I listened to Bhattacharya on Steve Bannon's "War Room" podcast. If you want to know how it went, see the following email that I just sent. 1/13

Jeff Vierstra was likely doomed by his DNA. A radical experiment gave him a chance to rewrite his fate — before ALS symptoms ever began. www.statnews.com/2025/07/28/a...

hotspot3: our chromatin accessibility peak caller is now a package – "pip install hotspot3" to try it out.

You might know that my life mostly revolves around skiing. I am organizing a 25 day sail & ski trip to Antarctica in Dec. 2025 and have space for 1-2 more people. We leave from Ushuaia, AR on the Tierra del Fuego (early Dec.) DM me for details and pass this around if you know anyone interested!

We have created a new DNase I- & ATAC-seq peak caller that uses an adaptive background model that controls for copy number variation & aneuploidy. It performs a per-nucleotide test (+FDR correction) and is very fast. Please try it out and give us feedback! github.com/vierstralab/...

A parting gift from Wouter. www.biorxiv.org/content/10.1...

This is cool and a blast from the past. Way back in grad school I spent like 10 months building a femtosecond laser to x-link TFs to DNA but could never get it to work.

This is a wild post for me to make because I havent shared this with many people. Today, the Lancet published the results of a trial for a novel ASO therapy for FUS-ALS which me and my siblings participated(-ing). You can read about my experience here: www.columbiadoctors.org/news/jeffs-s...

PSA: We just finished processing nearly all public ATAC-seq datasets from SRA (about 22,000 datasets). (Not?) Surprisingly, we had to throw-out nearly ~50% because they were low-quality (low signal-to-noise, duplicate rate, etc.). Check quality before analysis (TSS-enrichment is not sufficient!).

Two genome scientists at the end of the world!

There is still time to submit an abstract! The deadline is now extended to May 14.

Finally published! We developed an epigenomics to therapeutics screening approach that identifies naturally occurring elements that can titrate expression of transgenes at various levels including single elements stronger than the B-globin LCR. www.nature.com/articles/s41...

Happy to share the latest story from @arnaudkr.bsky.social's lab @embl.org! With @guidobarzaghi.bsky.social, we used Single Molecule Footprinting to quantify how often chromatin is accessible at enhancers after TF and chromatin environment changes! Check our preprint bit.ly/3XQMFxN + thread ⬇️ 1/11

Amazing game. The penalty shot -- WOW! www.youtube.com/watch?v=XC7B...

Not surprising that Evo2 (despite pre-print claims) can't even beat ~15yo approach for non-coding variant classification. How does a gimish of bacterial and metazoan genomes WITHOUT annotation going to learn this? Best to use functional data (i.e., ours -- DNase I data from 1000s of cell types).

Go to Chile! Awesome conference + the most beautiful landscapes in the world (sorry NZ!).

Hmm. I wonder if they will change what constitutes allowable indirect and direct expeditures. Will individual labs be able to negotiate lab space (i.e., rent)?

Looking for a Postdoc position in #Genomics at the interface of computational and molecular biology? -> The Rube lab at UC Merced is recruiting. I highly recommend you reach out! aprecruit.ucmerced.edu/JPF01874

This is actually good IMHO. The indirect costs dont go to researchers! 30-40% of the indirect costs go to subsidize university building depreciation and the bloated administrative state. If you dig into the budget of various universities, the true operation budget is like 15% anyhow.

Out today in Cell: a comprehensive map of Human Accelerated Region gene targets in human and chimpanzee neural stem cells. Thread: authors.elsevier.com/a/1kWzdL7PXu... www.cell.com/cell/fulltex...

Fantastic opportunity: 🚀 Calling early-career scientists! Apply for the 2025 ELISIR Scholar at EPFL. From outstanding PhD straight to group leader. Join an interdisciplinary research community to conduct independent research in any area of #lifesciences in Lausanne, CH 👉 go.epfl.ch/ELISIR

I just read the recent "Multiscale footprints reveal..." paper. (www.nature.com/articles/s41...). The claim by authors (below) is based on ONLY 2 regions (amongst 100k) in 5 cell types. They don't provide genome-wide footprint calls, so how can they make these claims?! i.e., where's the evidence?

There has been a couple of manuscripts released regarding transcription factor footprinting - or digital genomic footprinting (DGF) as we call it. I would like to put some of the claims, results and conclusions in context, since I have worked and published on this for ~15 years. 1/n

Just de-activated my Twitter/X account. Same feeling of relief when I did this ~10 years ago on the facepile app.

Going back to my hometown (Madison, WI) in January reminds me of why I live in the PNW now. Good thing I still own fleece lined pants!

A manuscript from my group finally got accepted -- had a long review process and the authors moved on nearly 2 years ago. Still proud of this work, where we show how one can translate epigenetic mapping efforts into useful tools for therapeutics. www.biorxiv.org/content/10.1...