iiinova — where your digital self keeps evolving

Jeff Vierstra @jeffvierstra.bsky.social · 08/10/2026

Just wrapped up writing about what I have learned studying the noncoding mammalian genome over the course of the last 17 years. Should be on bioRxiv mid next week!

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Jeff Vierstra @jeffvierstra.bsky.social · 07/10/2026

Been a while since I worked on the evolution of regulatory DNA. >12 years ago we described a phenomenon we coined "repurposing" where elements change cell activity patterns over time. ML has now enabled us to see the complex and subtle sequence changes underlying this.

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Maitreya Dunham @maitreya.bsky.social · 06/10/2026

Here's the ad for the Genome Sciences faculty positions ap.washington.edu/ahr/position...

ap.washington.edu

Position Details - Academic Personnel & Faculty

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Jeff Vierstra @jeffvierstra.bsky.social · 21/07/2026

I am sure we can see dimer TF occupancy (evident in example above), though they are very difficult to annotate because you would normally do so using motif matches. In any case, I am generally less interested the identify of the TFs bound vs. the overall binding structure.

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Jeff Vierstra @jeffvierstra.bsky.social · 16/07/2026

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 16/04/2026

Look for this manuscript to be online within the next couple of weeks on bioRxiv! Also, if you want to try out the data let me know as we are testing a new data packaging format.

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Jeff Vierstra @jeffvierstra.bsky.social · 16/04/2026

These data correspond to >1,000 individuals and we performed phased genotyping and allelic imbalance analysis with regulatory genomes (millions of SNVs). We have also uniformly processed and integrated >10,000 publicly available ATAC-seq datasets.

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Jeff Vierstra @jeffvierstra.bsky.social · 16/04/2026

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!

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Jeff Vierstra @jeffvierstra.bsky.social · 04/04/2026

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

youtu.be

Experimental treatments brings hope to ALS patients

YouTube video by CBS Mornings

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Jeff Vierstra @jeffvierstra.bsky.social · 10/03/2026

We have also created a data portal complete with a coding chatbot to access the raw and processed data (>4,000 reference DNase I and >10,000 ATAC-seq samples). Coming soon to bioRxiv!

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Jeff Vierstra @jeffvierstra.bsky.social · 10/03/2026

Using only training data from >4,000 human reference DNase I datasets we can also predict mouse DNase I. Also, it's readily tunable with the enormous amount of publicly available ATAC-seq data deposited to SRA.

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Jeff Vierstra @jeffvierstra.bsky.social · 10/03/2026

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 30/01/2026

I am well aware that one can find a sentence in the "Acknowledgments" section, but seems insufficient given that their whole project is only possible because of these resources.

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Jeff Vierstra @jeffvierstra.bsky.social · 30/01/2026

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...

nature.com

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...

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Jeff Vierstra @jeffvierstra.bsky.social · 27/11/2025

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

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bioRxiv Genomics @biorxiv-genomic.bsky.social · 16/11/2025

SPrUCE: Utilizing Ultraconserved Elements of DNA for Population-Level Genetic Diversity Estimation www.biorxiv.org/content/10.1101/202…

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Jeff Vierstra @jeffvierstra.bsky.social · 12/11/2025

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

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Jeff Vierstra @jeffvierstra.bsky.social · 08/11/2025

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...

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FragileNucleosome @fnucleosome.bsky.social · 03/11/2025

🥁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...

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Jeff Vierstra @jeffvierstra.bsky.social · 29/10/2025

Southern fjords of Chile on a boat.

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Juan Fuxman Bass @fuxmanlab.bsky.social · 17/10/2025

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!

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Jeff Vierstra @jeffvierstra.bsky.social · 18/09/2025

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....

nature.com

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...

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Polly Fordyce @pollyfordyce.bsky.social · 17/09/2025

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...

chemh.stanford.edu

Faculty Recruitment

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Jeff Vierstra @jeffvierstra.bsky.social · 01/09/2025

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 30/08/2025

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 29/08/2025

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 21/08/2025

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 13/08/2025

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

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Jeff Vierstra @jeffvierstra.bsky.social · 13/08/2025

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 13/08/2025

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).

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Jeremy Berg @jeremymberg.bsky.social · 11/08/2025

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.

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STAT @statnews.com · 28/07/2025

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...

statnews.com

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,

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Jeff Vierstra @jeffvierstra.bsky.social · 27/07/2025

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

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Jeff Vierstra @jeffvierstra.bsky.social · 12/07/2025

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!

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Jeff Vierstra @jeffvierstra.bsky.social · 08/07/2025

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 😂.

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Jeff Vierstra @jeffvierstra.bsky.social · 08/07/2025

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

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Jeff Vierstra @jeffvierstra.bsky.social · 08/07/2025

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

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Jeff Vierstra @jeffvierstra.bsky.social · 08/07/2025

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.com

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

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Jeff Vierstra @jeffvierstra.bsky.social · 03/06/2025

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 24/05/2025

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 23/05/2025

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.

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Jeff Vierstra @jeffvierstra.bsky.social · 23/05/2025

As an aside, this is my second clinical trial. The first one was for Ph+ ALL in which I was on Gleevac when I was 16, though I eventually relapsed and later got a BMT. I am a testament to the importance of NIH-funded research and how it can tangibly and profoundly changes lives.

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