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 👇

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

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.

Delighted to have our work on 🧬 resilience to 🩸cancer led by @g-agarwal.bsky.social & amazing collaborators, including @kharaslab.bsky.social, published in @science.org: www.science.org/doi/10.1126/... 🧵

Sunset on 2025. Wishing my Bluesky friends all the very best in the new year.

One of the most pleasant surprises of the past 20 years was the transformation of Wikipedia into arguably the most reliable general information source freely accessible to the public. It’s not perfect — I’ve certainly seen errors — but it’s kind of shockingly good. One might consider a donation.

I love this plot illustrating the famous generation-time effect on mutation rates with modern data!

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

www.cell.com/cell/fulltex... On how ~neutrally evolving CAG repeats over the lifespan eventually exerts neurodegenerative phenotype in Huntington’s disease.

All right it’s time for the annual “please tell us about one (or a few if you are ambitious) paper from 2025 that really impressed you and why we should all read it“! Go! If you tell us how it changed your view of the world and what makes it so powerful and consequential It would be excellent.

I guess the preprint came out in 2024 but it was published this year so I'll say this paper from @jeffspence.github.io and @hakha.bsky.social which is probably the paper that pleiotropy-pilled me the most. Really got me to think about what GWAS means www.nature.com/articles/s41...

As a (to me very enjoyable) part of this paper, we worked out what mutation-selection balance looks like in finite populations with varying degrees of inbreeding.

Now TWO great new papers on why frequencies of disease genes rarely match expectations Here was the first: www.nature.com/articles/s41...

Our latest preprint revisits the classic model of mutation-selection balance. Do human recessive genes fit Haldane's 100-year old model? This work is by the wonderful @jonj-udd.bsky.social, and co-mentored by @jeffspence.github.io www.biorxiv.org/content/10.6...

“Brilliance wrapped in modesty, decency, and good humor.” So true. 😭 May his memory be a blessing.

GWAS has been an incredible discovery tool for human genetics: it regularly identifies *causal* links from 1000s of SNPs to any given trait. But mechanistic interpretation is usually difficult. Our latest work on causal models for this is out yesterday: www.nature.com/articles/s41... A short🧵:

After time in the Bay Area, I’ve started a new role as Lecturer in the Department of Allergy and Rheumatology at the University of Tokyo. We’re the group of clinicians who see patients with autoimmune diseases, while researching new treatments and patient stratification. (continued)

Our latest collaboration with @jkpritch.bsky.social – led by joint post-doc Mineto Ota – is in @nature.com today: www.nature.com/articles/s41...

Our new ancient DNA paper has just been published! We present 28 new genomes from southern Africa - several of them high-coverage whole genomes. Exciting to be moving towards population-level representation of ancient southern African genetic diversity! www.nature.com/articles/s41...

Congratulations to Richard Durbin on being awarded our Genetics Society Medal!

It was a total pleasure to work with @roshnipatel.bsky.social on this, who really led the charge in all respects. Anyone interested in learning about the intersection of population genetics and statistical genetics should check out her new lab in Oregon!

Grateful to Isabella Alves & @cterminiphd.bsky.social for writing this fantastic N&V in @natcellbio.nature.com: www.nature.com/articles/s41... Nicely covers our 📰 led by della Volpe & co: www.nature.com/articles/s41...

The last work of my PhD is finally out: www.pnas.org/doi/10.1073/...! This work is about accurately estimating branch length in the Ancestral Recombination Graph (ARG), which is achieved by a really simple framework with minimal assumptions. (1/n)

Super excited about our schedule for BAPG at stanford on Dec 6. bapg2025.github.io/bapg2025stan... Amazing talks, a fabulous keynote, a lively poster session. A brilliant and interactive community. What’s not to love? 1/2 @sophiejwalton.bsky.social

We have 115 people signed up already for BAPG! Great representation across career stages too. If you want to attend don't forget to sign up. It is free but required. @sophiejwalton.bsky.social and I are looking through the wonderful talk submissions and will announce the talks shortly. Stay tuned!

An empirical approach to evaluating the prevalence of long-lived balancing selection in humans--and important limitations. Work by @hannahmm.bsky.social

Excited to share some new work led by grad student Sophie Walton (w/ @petrovadmitri.bsky.social). We used in vitro gut communities to study how natural selection acts on strains of the same species as they compete within larger communities. Check out Sophie's thread below for details!

Really cool paper that changed the way I think about what GWAS and Burden tests are doing, and also basically made me pleiotropy-pilled

Excited to share our latest work on the factors that determine what genes we find (and don't find!) in GWAS and burden tests. We describe a critical concept that we call *specificity*. Led by Jeff Spence and Hakhamanesh Mostafavi:

Bay Area Pop Gen conference Dec 6! One of my favorite conferences. Registration is free! Only controversy is how to pronounce BAPG (bap-guh is the right answer). docs.google.com/forms/d/e/1F...

Everything Jeff said except since we're hosting at Stanford it's pronounced BAP-G bsky.app/profile/jros...

Proud of the latest edition of my free intro biostats book. gitrepo: github.com/ybrandvain/b... book: ybrandvain.github.io/biostats/ Not complete but at a good point to take a break, and I think its quite usable dm me with comments , ideas etc

For population genetics and evolutionary biology folks in the Bay Area: the next BAPG will be hosted by Stanford CEHG and the Petrov lab at Stanford on 12/6. Registration is free but required. The deadline for talk submission is Nov. 16. Hope to see you soon! Pls RT! docs.google.com/forms/d/e/1F...

I'm recruiting a postdoc for my group (based in beautiful Eugene, OR). Please get in touch if you're interested, esp if you'd like to chat at #ASHG25!

I’ll be attending #ASHG25! I’m currently hiring for (i) a Senior Research Scientist or (ii) a Postdoc position in my lab. If you’re interested, please reach out to arrange a time to meet and discuss.

Save the date for a new conference exploring genomics for linking polygenic signals to mechanistic insights! Biology at Scale: From Variants to Cellular Programs & Functions is opening soon for registrations. #BiologyAtScale26 📍 Wellcome Genome Campus, UK 📅 29 June -1 July 2026 👉 bit.ly/4mYud02

Genetic architectures of #ComplexTraits vary widely. @yuvalsim.bsky.social @jkpritch.bsky.social @gs2747.bsky.social &co show these diffs arise from mutational target size & heritability per site; when controlled for, all tested traits have similar architectures @plosbiology.org 🧪 plos.io/47mZXqT

Blog post: Ancestry and Education Indirect, direct, confounded and quasi-causal. I write about a preprint by Wang et al, in which they look for associations with genetic ancestry in an admixed Mexican population. They found genetic effects for height and Type-II diabetes, but not for education.

I want to try something again at #ASHG25 this year: I'll block some time on Thursday and Friday afternoons to meet with trainees who would be interested to chat on any topic. I did this last year and it was great to meet a whole bunch of new people, at all career stages!

In these dark times, it comes as a rare pleasure to highlight @natanaels.bsky.social ‬ & @marcdemanuel.bsky.social's work on germline and somatic mutations in humans. 1/n www.biorxiv.org/cgi/content/...

🎉scverse conference 2025 Call for Abstracts DEADLINE EXTENDED! 🎉 We're excited to announce that the deadline to submit abstracts for the scverse Conference 2025 has been extended to September 15, 2025! 🧵 #scverse #scverse2025 #SingleCell #Conference

Delighted to share some wonderful work by our recent grad Matthew Aguirre on theoretical models of GRNs, and what eQTL data can teach us about these!

Excited to share our new preprint for the tskit_arg_visualizer Python package! ARGs can sometimes feel like a black box, so @yanwong.bsky.social and I have been developing a method to programmatically drawing these graphs. 🔗 arxiv.org/abs/2508.03958 1/6

🧠 Meet the keynote speakers for the 2025 scverse conference! Panos Roussos, Professor at Icahn School of Medicine at Mount Sinai 🧵 @panosroussos.bsky.social #scverse #scverse2025 #SingleCell #SpatialTranscriptomics #Conference #Keynote

Grateful for this terrific commentary by @tomonroe.bsky.social in @jclinical-invest.bsky.social on our paper that is out in final print format today: www.jci.org/articles/vie... Please check it out: www.jci.org/articles/vie...

"The molecular evolutionary basis of species formation revisited" by Molly Schumer (@mollyschumer.bsky.social) & colleagues "The origin of species has long fascinated biologists, but determining the genes [involved] has only recently become possible in non-model organisms." shorturl.at/wG0B5

Incredibly proud of this work where we developed a method for understanding the information contained in millions of genomes. Another example of NIH funded research.

Cool paper, and -- as expected by how similar the titles are -- dovetails nicely with our work (led by Margaret Antonio, Clemens Weiß, Ziyue Gao, and Susanna Sawyer): elifesciences.org/articles/79714

Bittersweet to be leaving @docedge.bsky.social after a wonderful postdoc, but excited to share that I'm joining @uoregon.bsky.social next month as an Assistant Professor in the Department of Data Science.