Jeff Vierstra

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....

Faculty Recruitment

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.

We also showed in a 2015 manuscript that the RREB1 site CCCCCACCC, also has a modest effect on HbF reactivation.

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).

Dear Dr. Bhattacharya: I have listened to your performance on the “War Room” podcast with Steve Bannon. The segment begins with a discussion of Secretary Kennedy’s recent cancellation of $500M worth of contracts related to mRNA vaccines. You say “You can’t have a platform where such a large percentage of the population distrusts the platform as we use it for vaccines and expect it to work.” Later, you make comments that might explain why a large segment of the percentage distrusts this platform. For example, you say that the vaccine was not protective against contracting COVID and cite your own case on COVID after being vaccinated. However, you fail to cite the evidence for the clinical trials that led to the Emergency Use Authorization.

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

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,

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!

Also, all the credit goes to @sboytsov.bsky.social and @sabromav.bsky.social.

We have applied this to ~4000 DNase I and >10,000 ATAC-seq (publicly available on SRA) datasets, and it seems to pass the "taste-test" as we call it. Maybe sometime in the future we will write this up -- though don't hold your breath 😂.

bsky.app/profile/jeff...

Here is slide demonstrating how it works w.r.t. to the highly aneuploid, yet very commonly used cell-line K562.

Of course. We first segment the genome by background (a proxy for copy number variation) and then call peaks.

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

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/...

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...

A parting gift from Wouter.

www.biorxiv.org/content/10.1...

Nice overview. I am individual #11 (the pre/asymptomatic one w/ EMG normalization) and my sisters were 5 and 8 (now since passed away). I have also been on the Ionis Ph3 trial for >3 yrs. The effect of this ASO, if administered at the right time is simply amazing.

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.

I should also mention that this whole story started randomly at a gene regulation conference in Barbados! Never say no to a conference, you never know what could result.