Our previously preprinted study "Influence of cis-regulatory elements on expression divergence in human segmental duplications" is now published in @genomeresearch.bsky.social! Please check it out: genome.cshlp.org/content/earl...

fixed your headline

Excited to see @jonj-udd.bsky.social's fantastic work out @genetics-gsa.bsky.social. Selection in _heterozygotes_ is the primary force shaping allele frequencies of loss-of-function mutations in humans, even in genes only associated with purely recessive diseases. 🧪🧬 doi.org/10.1093/gene...

Super interesting work by @jonj-udd.bsky.social and @jeffspence.github.io is now out in Genetics!

This paper also continues my streak of having the best experiences at #GENETICS (@genetics-gsa.bsky.social). Timely and incredibly thoughtful and thorough reviews. Thanks to @jnovembre.bsky.social and Nick Barton for handling our paper and the reviewers for helping us make our paper better.

Aspiring Eco-Evo PhD students - check out the Simons Graduate Fellowships! it's a full ride!! 🧪https://www.simonsfoundation.org/grant/simons-graduate-fellowships-in-ecology-and-evolution/

I am recruiting a PhD student (fully funded, 4yrs) to analyze modern 🧬 and ancient 🦴 genomic data from humans and domestic animals 🐑 Please share, I am happy to chat at #ICP2026 or #SMBE2026 this summer www.uu.se/en/about-uu/...

🏆 Congratulations to Tuuli Lappalainen, ESHG Award Lecturer 2026! In her Award Lecture, Professor Lappalainen will discuss the next steps in interpreting these effects and the tools that will help researchers uncover the molecular mechanisms underlying genetic variation. #Genetics #eshg2026

Excited to be at #PEQG26! I have a poster tonight on measuring selection on intraspecies variation in large microbial communities (415W), would love to hear what folks think!

#PEQG26 folks! I will be presenting my postdoc project with @jkpritch.bsky.social and @jeffspence.github.io about inferring population structure dynamics over time with tensor decomposition on ARG. The talk will be at the James Crow Talk session on Wednesday. Look forward to seeing everyone there!

@nature.com on Egli's human embryos base editing. www.nature.com/articles/d41... Quotes me on worries about risky efforts. Egli says that would be premature; yes, that's my point. I also agree w/Fyodor Urnov's that preimplantation testing is (almost always) a better solution even if this proves safe

Our new paper doi.org/10.1098/rspb... on long-term genetic threats to small populations finds that "mutational meltdown" (bad mutations fixing) is less of a problem than "mutational drought" (too few good new mutations) @wmawass.bsky.social @uliseshmc.bsky.social @jeremyjberg.bsky.social 1/5

Combined Optical Pooled Screens and Perturb-seq! Great new work by Romain Lopez & Taka Kudo. This is one of a series of papers from our lab (here, with Aviv Regev) using perturbations to interpret human genetics; a key revelation for me is how transferable the mouse perturbs are to human genetics.

🚀 We are introducing PerturbPair (with Taka Kudo) — a platform that combines parallel Perturb-seq and optical pooled screening (PerturbView) in primary cells to systematically map at massive scale how genetic perturbations reshape cellular states across modalities. www.biorxiv.org/content/10.6...

Pareto curves in track racing: So, this weekend I was playing around in Claude Code with a database of track times (all Diamond Leagues and global champs from last 12 years). I really like this viz of tactics in the men's 5000m, one of the most tactical events in track.

Our new paper is out! Tweetorial coming soon!

We built a joint experimental and computational platform for scalable multi-modal single-cell chemical screens — profiling RNA, protein (including phospho-signaling), and chromatin accessibility responses to thousands of small molecule perturbations in parallel. www.biorxiv.org/content/10.6...

Nikhil Milind's new paper tackles an intriguing paradox: Why does the genome-wide deletion load, and duplication load, tend to push most traits in the SAME direction?? Very proud of this, his first lead-author paper at Stanford!

I'm excited to share that our work studying gene dosage response curves (GDRCs) is now out in Cell Genomics (@cellpress.bsky.social). www.cell.com/cell-genomic... [1/n]

Happy to share that this is now out in Cell Genomics and a featured paper for Multi-Journal Submission from @cellpress.bsky.social — many thanks to the editorial team + our reviewers! Short recap + some further thoughts on the paper ⬇️ [1/7] www.cell.com/cell-genomic...

Some deep work by my former student Matthew Aguirre on what the properties of cis- and trans eQTLs can teach us about the structure of gene regulatory networks!

This is a fantastic mentoring opportunity!

An amazing opportunity to work with @tamigj.bsky.social and make a positive social impact with your comp bio skills!

I am excited to share my first paper, our new preprint: www.biorxiv.org/content/10.6... with @arbelharpak.bsky.social and @docedge.bsky.social. Family GWAS provides direct genetic effect estimates and is increasingly important. But how much can we trust these estimates? (1/15)

🧬New from @lukeoconnor.bsky.social & Sella! 📄Principled measures and estimates of trait polygenicity

As I process large gwas summary files I am so thankful, yet again, for tabix. So fast.

Thrilled to see this out. What started out as a chat several years back with @drfejzo.bsky.social about leveraging publicly available data on hyperemesis gravidarum GWAS turned into a wonderful collaboration with April Shu, @mvaudel.bsky.social, @xwww.bsky.social and many others! rdcu.be/fdl9k

Some slides from a recent talk on missing heritability. www.dropbox.com/scl/fi/kvogj...

Gonna be some rad science -- @mollyschumer.bsky.social keynote and a bunch of good talks and posters. And I'll personally pay the registration of anyone who wants to come (it's free).

Differences in evolutionary parameters have important implications for interpreting GWAS results. With the inferred parameters, we reproduced the period when major depression yielded no GWAS discoveries, and we predict that psychiatric disorders will eventually reach higher saturation points. 🧵12/n

This work was done in collaboration with my wonderful mentors @yuvalsim.bsky.social , @jeffspence.github.io , @gs2747.bsky.social , and @jkpritch.bsky.social . doi.org/10.64898/202... 🧵2/n

Monthly median Received to Accepted time (days) at Nature Genetics

Why do schizophrenia GWAS signals look so flat across the genome? In our recent preprint, we explored why psychiatric disorders — and, more broadly, brain-related traits involving the central nervous system — appear to have unusual genetic architectures. 🧵1/n

We invite you to join our seminar at UCSF Mission Bay campus with Hakhamanesh Mostafavi from NYU Grossman School of Medicine humangenetics.ucsf.edu/ihg-seminar-...

It's out! I hope this work encourages folks to move beyond a standard "one variant, one gene" QTL paradigm and consider proxitropic variant effects. Big thanks to the reviewers and editors at @ajhgnews.bsky.social for their help! @sbmontgom.bsky.social www.sciencedirect.com/science/arti...

Excited to share our new preprint from the @arbelharpak.bsky.social Lab! How do recruitment into genetic studies and study characteristics impact what we infer about the genetic bases of traits, and what are the consequences? (1/21) www.biorxiv.org/content/10.6...

If you like larger sample sizes, then do check out our reprocessed and fine mapped cis-eQTLs and cis-sQTLs (leafCutter and MAJIQ!) from the INTERVAL cohort (whole blood, n up to 4,729)! zenodo.org/records/1795... These will be on the eQTL Catalogue FTP soon as well. cc @yosephbarash.bsky.social

We used a similar design in this paper: www.sciencedirect.com/science/arti... Found that in cis-MR with multiple colocalising instruments (i.e. multiple indepdent signals colocalise between eQTL and pQTL traits) sign concordance was around 95%:

Your numbers after stringent colocalization seem quite consistent with theirs (tagging @nikhilmilind.dev @jkpritch.bsky.social) . Colocalization is clearly needed, but it kills recall and that's a difficult thing to get around with standard sample sizes...

Clever use of proteomic data to stress-test TWAS and QTL colocalization methods, revealing a high false sign rate. This hypothesis about high-LD and cross-tissue confounding is particularly interesting:

Happy to share our new preprint from @sashagusevposts.bsky.social and @nmancuso.bsky.social labs! We introduce Mr. PEG, a framework integrating perturbational screens, eQTL, and GWAS data to identify mediating genes for complex traits. (1/n) www.medrxiv.org/content/10.6...

New method from our group for identifying disease-mediating genes using perturb-seq, eQTL, and GWAS data. Check out the thread:

New preprint alert: we use sign errors as a test of how well TWAS works. Very worryingly we find that TWAS gets the sign wrong around 1/3 of the time (compared to 50% for pure guessing). You can read more about our analysis here, and what we think is going on 👇

How well does TWAS estimate a gene’s direction of effect on a trait? We think of this as an important stress-test for the accuracy of TWAS. In a new pre-print, we find that TWAS gets the sign wrong around 20-30% of the time! doi.org/10.64898/202... 1/n

I'm just delighted to announce our new preprint on genome-scale perturb-seq in CD4+ T cells. We learned both general lessons about the power of perturb-seq, and specific lessons about T cell biology. Led by amazing postdocs Emma Dann and Ronghui Zhu, with my wonderful collaborator Alex Marson.

This is only the beginning: with the help from lattice team @biohub.org, we made all the data available. We hope this dataset will be a foundational resource for systems immunology, human genetics, "virtual cell" modeling efforts, and immunotherapy development.

Together with @ronghuizhu.bsky.social, we are thrilled to present our new perturb-seq study of 22M primary CD4+ T cells, across donors and timepoints – the result of a decade-long collaboration between the Marson @marsonlab.bsky.social and Pritchard @jkpritch.bsky.social labs 🧵 tinyurl.com/gwt2025

Happy to highlight an essay I wrote together with @marcdemanuel.bsky.social, @natanaels.bsky.social and Anastasia Stolyarova, trying to think through what sets the mutation rate of a cell type in an animal species: www.biorxiv.org/content/10.6... 1/n

We wrote the Strain on scientific publishing to highlight the problems of time & trust. With a fantastic group of co-authors, we present The Drain of Scientific Publishing: a 🧵 1/n Drain: arxiv.org/abs/2511.04820 Strain: direct.mit.edu/qss/article/... Oligopoly: direct.mit.edu/qss/article/...

High false sign rates in transcriptome-wide association studies https://www.biorxiv.org/content/10.64898/2025.12.19.695550v1