Jeff Vierstra
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jeffvierstra.bsky.social
Jeff Vierstra
@jeffvierstra.bsky.social
380 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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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...
Reposted by Jeff Vierstra
🥁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.
Reposted by Jeff Vierstra
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....
Reposted by Jeff Vierstra
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.
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.
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
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).
Reposted by Jeff Vierstra
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
hotspot3: our chromatin accessibility peak caller is now a package – "pip install hotspot3" to try it out.
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
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 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 😂.
Here is slide demonstrating how it works w.r.t. to the highly aneuploid, yet very commonly used cell-line K562.
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.
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
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.