Jeff Vierstra
@jeffvierstra.bsky.social
370 followers 400 following 130 posts
Senior Investigator @ Altius Institute for Biomedical Sciences. Research: High-resolution mapping of chromatin structure & function. Fun: Mountain shenanigans and skiing turns all year. Seattle, USA/Patagonia Chilena (🇺🇸🇨🇱). http://vierstra.org
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jeffvierstra.bsky.social
The last couple of years has been wild. Thanks to Jason Mast and @statnews.com for telling my family's story. I am very fortunate to have been in the right place and right time.

www.statnews.com/2025/07/28/a...
jeffvierstra.bsky.social
Didn't take long for some grifting lawyers to jump in. 😱
jeffvierstra.bsky.social
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....
Reposted by Jeff Vierstra
pollyfordyce.bsky.social
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
jeffvierstra.bsky.social
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.
fnucleosome.bsky.social
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...
Fragile Nucleosome Fall Seminars:
September 10    Grace Bower, Kvon Lab @ UC Irvine, USA
    Jennifer Phillips-Cremins, UPenn, USA

September 24    Ali Wilkening, Sanulli Lab @ Stanford, USA
    Juanma Schvartzman, Columbia University, USA

October 8    Sanim Rahman, Greenberg Lab @ UPenn, USA
    Alex Federation, Talus Bio, USA

October 22    Alice Laigle, Croll Lab @ University of Neuchâtel, Switzerland
    Seungsoo Kim, UC Irvine, USA

November 5    Hannah Long, University of Edinburgh, UK
    Jeff Vierstra, Altius Institute, USA

November 19    Ishtiaque Hossain, Pastor Lab @ McGill, Canada
    Sarah Teichmann, University of Cambridge, UK

December 3    María Mariner Faulí, Rada Iglesias Lab @ IBBTEC, Spain
    Jonathan Henninger, Carnegie Mellon, USA

December 17    Rebecca Berrens, Oxford University, UK
    Jean-Benoit Lalanne, University of Montreal, Canada
jeffvierstra.bsky.social
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.
jasonmast.bsky.social
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.
Did a drug prevent this man’s ALS?
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
jeffvierstra.bsky.social
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.
jeffvierstra.bsky.social
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.
jeffvierstra.bsky.social
We also showed in a 2015 manuscript that the RREB1 site CCCCCACCC, also has a modest effect on HbF reactivation.
jeffvierstra.bsky.social
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.
jeffvierstra.bsky.social
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).
Reposted by Jeff Vierstra
jeremymberg.bsky.social
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
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.
jeffvierstra.bsky.social
The last couple of years has been wild. Thanks to Jason Mast and @statnews.com for telling my family's story. I am very fortunate to have been in the right place and right time.

www.statnews.com/2025/07/28/a...
jeffvierstra.bsky.social
hotspot3: our chromatin accessibility peak caller is now a package – "pip install hotspot3" to try it out.
jeffvierstra.bsky.social
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
jeffvierstra.bsky.social
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!
jeffvierstra.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 😂.
jeffvierstra.bsky.social
jeffvierstra.bsky.social
Here is slide demonstrating how it works w.r.t. to the highly aneuploid, yet very commonly used cell-line K562.
jeffvierstra.bsky.social
Here is slide demonstrating how it works w.r.t. to the highly aneuploid, yet very commonly used cell-line K562.
jeffvierstra.bsky.social
Of course. We first segment the genome by background (a proxy for copy number variation) and then call peaks.
jeffvierstra.bsky.social
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
jeffvierstra.bsky.social
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.
jeffvierstra.bsky.social
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.
jtrend.bsky.social
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...
🧵
The human proteome with direct physical access to DNA
Zero-distance photo-crosslinking reveals direct protein-DNA interactions in living cells, enabling quantitative analysis of the DNA-interacting proteome on a timescale of minutes with single-amino-aci...
www.cell.com
jeffvierstra.bsky.social
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.