Delighted to share our latest research from the 23andMe Research Team, just published in @nature.com ! We looked at data from >27,000 participants to uncover how human genetics influences weight loss efficacy and side effects of GLP-1 medications like semaglutide. A short thread 🧵👇

Brian and I were grad students together. He's a mensch, and the goons who torpedoed his funding and his livelihood are contemptible.

I hope this isn’t the end of Brian’s career but if there’s something people can do, it’s use his material in your classes (thankfully carried on by @robbeewedow.bsky.social and company)

I’m so glad someone covered this story. Brian is an amazing scholar and person who I’ve been blessed to be able to get to know, even a little. What happened to him is awful

Biodiversity includes genetic diversity within species. A framework for predicting changes in genetic diversity under realistic habitat change scenarios suggests that species have already lost up to 13% of nucleotide genetic diversity. In PNAS: https://ow.ly/s0R150YCr5K

Distilling the most confident mutation effect scores across different versions of the same protein language model results in a superior sequence-only variant effect predictor. @vntranos.bsky.social www.nature.com/articles/s41...

Never seen a more compelling endorsement for submitting your work to GENETICS @genetics-gsa.bsky.social

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).

Our paper is out! We compared introgression maps, both across populations and at the individual level. Some consistencies were observed across maps: A core set of genomic regions, lower background selection in introgressed regions, and some phenotypes were enriched across multiple maps. (1/3)

Meiosis faces a fundamental problem: It must repair hundreds of DNA double-strand breaks while executing a transcriptional programme essential for gamete development. But many of these breaks occur in genes. So how are these two processes reconciled? www.biorxiv.org/content/10.6...

We are destroying species' habitats, leading to a mass extinction event. This habitat destruction also reduces the genetic diversity _within_ species. Our latest work develops quantitative models to predict how much genetic diversity has been and _will be_ lost. 🧬🧪🧵 www.pnas.org/doi/10.1073/...

Delighted to share our latest preprint: Julie Zhu identifies a surprising reason why the genetic architecture of brain-related traits is so different than other traits. Check it out!

So why is it low-dimensional? Are adaptive mutants low-dimensional ONLY near their local fitness peak? What would happen if we took the same set of mutants, and the same set of environmental perturbations, but we applied them around some distant “base” environment? (8/n)

Really excited that this major work from my PhD is finally published in @plosbiology.org ! In it, we were trying to tackle a fundamental question in evolution - how do genetic mutations map onto evolutionary fitness? (1/n) journals.plos.org/plosbiology/...

Join us for talks across our cross-campus institutes, a poster session with hors d'oeuvres, and trainee awards for best poster and best short talk ($1,000 each)! humangenetics.ucsf.edu/pcb-ihg-and-...

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

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

Predicting the effect of a #mutation on #fitness is hard. @oliviamghosh.bsky.social @petrovadmitri.bsky.social &co use fitness effects of adaptive yeast mutants to show that underlying genotype-phenotype-fitness maps are low-dimensional but context-dependent @plosbiology.org 🧪 plos.io/4dLy2Ez

Congratulations to my @UCSF colleague Geeta Narlikar and my grad school classmate Abby Dernberg on this well-deserved honor (and everyone else too)! It’s good to have something to celebrate in these challenging times.

👀 Absolute banger paper. Leveraging cattle/pig GWAS/eQTL to help explain the missing regulatory gap in humans. Consistent with previous works, selection makes identifying relevant eQTLs in humans challenging. www.biorxiv.org/content/10.6...

Humans are such a horrible study system, it’s a shame they’re us

Insightful new work on the genetic architectures of brain-related traits, by @huishengzhu.bsky.social @yuvalsim.bsky.social @jeffspence.github.io @jkpritch.bsky.social, showing that “the genetic architectures of complex traits are shaped by the tissues through which these traits are mediated” 🧪🧬

“Human ancestors interbred with two distinct populations of distant relatives” nice new preprint by @alanrogers.bsky.social @colinmbrand.bsky.social @timwebster.bsky.social showing that “archaics” & “moderns” interbred with two distinct “superarchaic” populations 🧪🧬💀

Excited to share a recent publication co-authored with Dr Chris Donohue, former historian of genetics/eugenics at the National Human Genome Research Institute. It's an overview of how modern population genetics contributes to its own weaponization. onlinelibrary.wiley.com/doi/epdf/10....

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-...

I used a combination of claude and codex, as well as the excellent base code from our jaxQTL project, to drive glmax. glmax is a jax-based GLM framework that is jit-compiled and end-to-end differentiable. It leverages implicit function theorem for improved autodiff. mancusolab.github.io/glmax/

We (with @yanwong.bsky.social) are advertising a 3 year postdoc position for a project on ARG inference and methods! Based at Oxford stats. Closing date noon 7 April, full details at my.corehr.com/pls/uoxrecru...

Just created a new postdoctoral position at UCSF doing cardiovascular deep learning and common-variant genetics in my lab. Please take a look at the posting and send me an email if interested! postdocs.ucsf.edu/postdoctoral...

Some more thoughts on why this outbreak (large, happening quickly, in one place) might be happening: johnlees.me/posts/menb-o... Perhaps strain + immunity + high transmission

Here's our R package for interacting with WGS derived GWAS summary statistics with many rare variants (from e.g. UKB or AofUs). It uses duckdb underneath so it's fast. Includes some helpful tie ins to Open Targets / Encode Screen / Ensembl APIs for annotation. weinstocklab.github.io/gwasplot/ind...

We invite you to join our seminar at UCSF Mission Bay campus with Paul Norman from @cuanschutz.bsky.social humangenetics.ucsf.edu/ihg-seminar-...

📣New from Kumar & co! 📄MetaGLIMPSE: Meta-imputation of low-coverage sequencing data for modern and ancient genomes 🖥️ github.com/karinkumar/M...

Nice to see this out! Great work by Kiran Kumar and Sebastian Zöllner!

Great to see this work out, led by Jon Rosen and co-supervised Karen Mohlke @klmohlke.bsky.social! Connecting to some recent threads here:

Finally, today's offering! www.biorxiv.org/content/10.6... This began life as a very different project which failed because we couldn't agree on defining eqtl sharing across cohorts. So two young members of the lab dug deeply into this - first @ijbeasley.bsky.social, then @patrickgibbs.bsky.social

My preprint on keju, a statistical tool for Massively Parallel Reporter Assay (MPRA) data, is out! keju improves sensitivity, calibration, and reliability over previous methods by closely modeling important uncertainty sources in MPRAs. Check it out: www.biorxiv.org/content/10.6... (1/n)

Power is a major confounder in the analysis of cross-ancestry 'portability' in human eQTLs https://www.biorxiv.org/content/10.64898/2026.02.26.708346v1

My lab is seeking to co-hire another postdoctoral fellow with the @shaonsengupta.bsky.social team. See details below! careers.chop.edu/us/en/job/10...

@pratikkatte.bsky.social and I just released Lorax 🌲, a tool for interactive exploration of biobank-scale ancestral recombination graphs (ARGs). If you’ve ever wanted to scroll across the ancestries of thousands of genomes… this is for you.

Two post-doc post in ARG space and loads of internal and external collaboration Postdoctoral Research Associate in quantitative genomics elxw.fa.em3.oraclecloud.com/hcmUI/Candid... Postdoctoral Research Associate in quantitative genetics and breeding elxw.fa.em3.oraclecloud.com/hcmUI/Candid...

Super cool to see more nuanced models of heritability and genetic architecture for medically relevant definitions.

postdoc recruitment still open!

Can we simulate realistic evolutionary trajectories and “replay the tape of life”? In this work, we propose a flexible, generalizable deep learning framework for modeling how the entire protein sequence evolves over time while capturing complex interactions across sites. 1/n doi.org/10.64898/202...

The last chapter of my PhD is finally out !!!! In the same species, on neighboring islands, we see radically different warning colors emerge. Evolution in action: Selection-driven color variation in the aposematic strawberry poison frog, Oophaga pumilio: Current Biology www.cell.com/current-biol...

The next BAPG has been announced! April 11 at Davis organized by the inimitable @jrossibarra.bsky.social! bapg-conference.github.io

Our Perspective paper "Toward informed batch correction for single-cell transcriptome integration" is out now in Nature Computational Science! 📄✨ We review a decade of batch-correction methods and propose a move from "blind" integration to "informed" modeling. 🧵👇 🔗 rdcu.be/e4cSp

I used my JAX-based skills for codex to port the excellent Python3 LDSC spec to JAX and Polars. My intent here was to stress test my JAX skill definitions and find how I could improve rules and contexts--NOT to develop a replacement github.com/mancusolab/j...

Fun news! @gcbias.bsky.social and I are teaching a 2-week online population genetics workshop this summer to raise money for the Center for Population Biology at UC Davis. We're trying to gauge interest -- please fill this out if you might be interested! And please share broadly!

Buscamos una/un postdoc entusiasta y motivada para unirse al grupo de Paleogenómica y Biología Evolutiva en @liigh-unam.bsky.social para liderar un proyecto enfocado a muestras humanas prehispánicas. Interesadxs ​por favor enviar CV y ​​carta de intención a [email protected]. Por favor #RT.

(Observation 3) Qualitative trends of portability can depend on the measure of prediction accuracy used. For some traits our measure of group-level prediction accuracy often drops where at the individual level, it increases. (19/27)