Jeff Vierstra
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
- 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...
- 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.
- Getting up-close and personal with the Patagonian fjords near the Beagle Channel.
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- 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...
- 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 VierstraIt’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 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...
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- 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.
- 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.
- We also showed in a 2015 manuscript that the RREB1 site CCCCCACCC, also has a modest effect on HbF reactivation.
- 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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- Reposted by Jeff Vierstra[Not loaded yet]
- 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/...
- 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/...
- Here is slide demonstrating how it works w.r.t. to the highly aneuploid, yet very commonly used cell-line K562.
- 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 😂.
- Also, all the credit goes to @sboytsov.bsky.social and @sabromav.bsky.social.
- A parting gift from Wouter. www.biorxiv.org/content/10.1...
- 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.
- 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...
- My family carries a mutation that causes a particularly aggressive form of ALS, which wiped out an entire generation (my mother and all of her 3 siblings) and it has now taken the lives of two of my sisters (in their early 40s) who were also on this study.
- The results of this study are amazing, it substantially extended the lives of my sisters, one participant had phenotypic reversion, and fortunately I am still overt-symptom free (and had even reversion of EMG irregularities).
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View full threadI 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.
- 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!).
- Two genome scientists at the end of the world!
- Reposted by Jeff VierstraThere is still time to submit an abstract! The deadline is now extended to May 14.
- Like regulatory genomics? Don’t miss this very fun meeting! May 7 is the deadline for early registration and abstract submission www.asbmb.org/meetings-eve...
- Finally published! We developed an epigenomics to therapeutics screening approach that identifies naturally occurring elements that can titrate expression of transgenes at various levels including single elements stronger than the B-globin LCR. www.nature.com/articles/s41...
- Of note, we showed that these sequences work in correcting b-thalassemia phenotype in patient derived HSPCs and showed the activity is erythoid cell selective in mouse xenograft studies.
- I think this study exposes a well-known yet often ignored problem -- cell-context matters. Screening erythroid candidate sequences in a cancer line (K562) gives completely different results than primary cells. In fact we would have discarded these sequences if only measured in K562.
- Screening is hard in primary cells given the considerable positional effects when using lentivirus. We estimate that you need roughly 800 integrations per sequence accurately estimate effect size. This hard to do in prim. HSPCs in which 5M is a lot cells, and really limits you input library size.
