You dont need advanced ML models to see base-resolution transcription factor occupancy and element-wise cis-regulatory logic. Just turn to a 40yo technology and basic stats. Still waiting for a structural biologist to help with 3d-modeling of composite regulatory DNA elements from DNase I profiles.

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

Experimental treatments brings hope to ALS patients

YouTube video by CBS Mornings

youtu.be

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...

Advancing regulatory variant effect prediction with AlphaGenome - Nature

AlphaGenome, a deep learning model that inputs 1-Mb DNA sequence to predict functional genomic tracks at single-base resolution across diverse modalities, outperforms existing models in variant effect...

nature.com

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....

The accessible chromatin landscape of the human genome - Nature

An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data s...

nature.com

Open Targets@opentargets.org · 11mo ago

The Open Targets Platform autumn release is out! 🍂 We have ingested the full dataset of over 13 million enhancer-gene regulatory interactions in the human genome across 1,458 DNase-seq experiments covering 369 cell types and tissues from the ENCODE-rE2G model blog.opentargets.org/open-targets...

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...

Faculty Recruitment

chemh.stanford.edu

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.

FragileNucleosome@fnucleosome.bsky.social · 11mo ago

We're super excited to announce the entire lineup for the Fall season of Fragile Nucleosome Seminars, starting on Sept 10th at 1200 EDT / 1600 UTC with @gracebower.bsky.social and @creminslab.bsky.social! register here for the entire series: us06web.zoom.us/webinar/regi...

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.

Jason Mast@jasonmast.bsky.social · last yr.

A 🧵: Last week, I wrote about Jeff Vierstra, who carries the gene for a devastating, rare form of ALS. The disease killed his mom and all three of her siblings, along with relatives dating back to the 1800s. Then, in 2020, two of his sisters began showing symptoms.

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...

Did a drug prevent this man’s ALS?

For over an hour, Jeff Vierstra lay still in Columbia University’s ALS clinic, as a doctor poked him ankle-to-throat with an electric needle. Sometimes,

statnews.com

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

Jeff Vierstra@jeffvierstra.bsky.social · last yr.

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/...

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/...

GitHub - vierstralab/hotspot3: A chromatin accessibility peak caller with an adaptive background model

A chromatin accessibility peak caller with an adaptive background model - vierstralab/hotspot3

github.com

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

Epilogos: information-theoretic navigation of multi-tissue functional genomic annotations

Functional genomics data, such as chromatin state maps, provide critical insights into biological processes, but are hard to navigate and interpret. We present Epilogos to address this challenge by of...

biorxiv.org

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.

Jakob Trendel@jtrend.bsky.social · last yr.

Excited our paper is out in Cell @cp-cell.bsky.social! 🧬⚡ DNA photo-crosslinking proteomics in living cells 🎯 Pinpoints protein-DNA interactions to single amino acids 🌎 Globally quantifies DNA binding for >1800 proteins at a timescale of minutes 🔗 www.cell.com/cell/fulltex... 🧵

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!).