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Jonathan Pritchard

@jkpritch.bsky.social
8K followers 1.1K following 349 posts

My lab at Stanford studies human population genetics and complex traits.

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Reposted by Jonathan Pritchard
Molly Przeworski @mollyprz.bsky.social · 16/09/2026
Work by Matin Saeidi and @will-milligan.bsky.social modeling mutator allele dynamics in humans, and asking what types of mutators we should expect to find by surveying offspring in trios.
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Reposted by Jonathan Pritchard
Piper Below @piperbelow.bsky.social · 23/09/2026
Very excited to see these three important papers published. This News and Views provides a short summary, for those interest in this new transcriptomic resource for the prefrontal cortex! www.nature.com/articles/d41...
nature.com
Vast cellular gene-expression atlas could transform how scientists understand brain ageing and disease
Single-nucleus RNA sequencing captures molecular changes in the prefrontal cortex across the lifespan and in health and disease.
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Reposted by Jonathan Pritchard
Richard Sever @richardsever.bsky.social · 21/09/2026
"any answer to 'is AI good for science' that neatly fits into a single yes or no is unserious...here is an invitation to join the real discussion" Thoughtful piece by @blekhman.bsky.social on a subject that provokes knee-jerk responses for and against. blekhman.substack.com/p/the-ai-dis...
blekhman.substack.com
The AI Discourse in Academia is Toxic. It Doesn’t have to be.
You are allowed to have a nuanced opinion about AI
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Harmit Singh Malik @harmitmalik.bsky.social · 21/09/2026
Thanks to the generosity of the Bezos Family Foundation, @basicsci.fredhutch.org is excited to announce a new search to recruit a Bezos Family Distinguished Scholar : apply.interfolio.com/193655
apply.interfolio.com
Apply - Interfolio {{$ctrl.$state.data.pageTitle}} - Apply - Interfolio
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Yun Deng @yundeng.bsky.social · 14/09/2026
I am excited to share that I will be joining the Baker Institute for Animal Health and College of Veterinary Medicine at Cornell University as an Assistant Professor next spring! I am grateful to my mentors and colleagues who have supported me throughout this journey.
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Jeff Spence @jeffspence.github.io · 14/09/2026
@roshnipatel.bsky.social and I wrote about using biobanks to learn about evolution, and how those findings shape interpretations of association studies. We focused on estimating evolutionary constraint and relating relating selection on variants to selection on traits and include open questions.
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Doc Edge @docedge.bsky.social · 12/09/2026
Please repost: My department (quantitative and computational biology at the University of Southern California) is hiring a teaching-track faculty member. The new hire will focus on teaching statistics courses to biology students. Apply by Dec 1 usccareers.usc.edu/job/los-ange...
usccareers.usc.edu
Full-Time, Teaching-Track Faculty Position in Quantitative and Computational Biology at USC
Learn more about applying for Full-Time, Teaching-Track Faculty Position in Quantitative and Computational Biology at USC
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Graham Coop @gcbias.bsky.social · 10/09/2026
I’m looking to hire an NIH funded postdoc to join our lab here at Davis (please RT). Ongoing areas of interest include: 1) polygenic signals of selection from time series, ARGs, GWAS, etc 2) The interpretation of GWAS, polygenic scores, & sources of confounding
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Tom Near @tjnear.bsky.social · 29/08/2026
1/11 🐟 2nd new preprint today from @chasedbrownstein.bsky.social We investigated how losing the swim bladder, the organ that most fishes use to control their buoyancy, has shaped the diversity of ray-finned fishes over 90 million years of Earth history. The results surprised us. 🧵
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Jonathan Pritchard @jkpritch.bsky.social · 29/08/2026
Genome-scale perturb-seq in human T cells. Our fantastic postdocs @ronghuizhu.bsky.social and @emmamarydann.bsky.social have done great work here to show the power and opportunities of perturb-seq in primary cells. This is part of a wonderful long-term collaboration with @marsonlab.bsky.social
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Emma Dann @emmamarydann.bsky.social · 28/08/2026
Our work on systematic perturb-seq of primary human T cells is now out in Cell 🎉 www.cell.com/cell/fulltex... It's been a privilege to work with @ronghuizhu.bsky.social between @jkpritch.bsky.social @marsonlab.bsky.social labs, with a dream-team of co-authors ❤️ Highlights in preprint thread👇
cell.com
Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits
A dynamic atlas of gene regulation was generated by perturbing every expressed gene across 22 million primary human CD4+ T cells under resting conditions and following re-stimulation. The resulting ma...
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Jesse Engreitz @jengreitz.bsky.social · 18/09/2025
Excited for a major milestone in our efforts to map enhancers and interpret variants in the human genome: The E2G Portal! e2g.stanford.edu This collates our predictions of enhancer-gene regulatory interactions across >1,600 cell types and tissues. Uses cases 👇 1/
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Julia M. Rohrer @dingdingpeng.the100.ci · 24/08/2026
Just read this very cool blog post by @jkpritch.bsky.social about recessive genes. Very interesting topic and I really appreciate the accessible explanation of a paper that I'd never dare to pick up myself. jkpritchard.substack.com/p/are-any-ge...
jkpritchard.substack.com
Are any genes truly recessive?
Journal club: Judd et al 2026 -- a surprising result about natural selection in recessive genes
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vincentholst.bsky.social @vincentholst.bsky.social · 14/08/2026
As promised, we now share some details why it took 32 months to get this Matters Arising published, and, since many asked, share some comments on the reply to our critique. All details can be found in this small FAQ vincentholst.github.io/the_curious_.... Below is a summary 🧵
vincentholst.github.io
The Curious Case of the Declining Disruption’s Disappearance
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Yun Deng @yundeng.bsky.social · 15/08/2026
The first manuscript from my postdoc is out (doi.org/10.64898/202...)! We introduce 𝐭𝐢𝐦𝐞-𝐬𝐭𝐫𝐚𝐭𝐢𝐟𝐢𝐞𝐝 𝐬𝐭𝐚𝐭𝐢𝐬𝐭𝐢𝐜𝐬 for studying population structure change over time, with the temporal resolution of Ancestral Recombination Graphs (ARGs). Joint with @jkpritch.bsky.social and @jeffspence.github.io. 1/n
google.com
Coalescent-Based Time-Stratified Statistics Reveal Population Structure Dynamics using the Ancestral Recombination Graph
Many questions in population genetics are concerned with reconstructing evolutionary history through time, such as inferring how population structure has changed throughout the past. Yet, many existing approaches have only an implicit temporal component, using quantities such as allele frequency or haplotype length as rough proxies for age. Recent advances in the inference of Ancestral Recombination Graphs (ARGs) have made it possible to estimate the entire sequence of local genealogies along the genome. These genealogies explicitly encode how samples are related to each other at different time points in the past, enabling the inference of how population structure has changed over time. To this end, recent work has used ARGs to define time-stratified versions of widely-used population genetics summary statistics in an attempt to capture the population structure present within a particular time window. Here, we show that naive approaches result in statistics that cannot be interpreted solely in terms of the population structure present within the time window they are targeting. To address this problem, we introduce a framework of coalescent-based time-stratified statistics, which use coalescence probabilities to partition classical summary statistics into interval-specific contributions. Using coalescent simulations, we demonstrate that these statistics accurately isolate population structure at different temporal depths and avoid spurious signals. Our results highlight the necessity of integrating coalescent theory into ARG-based temporal analyses and provide a principled and practical foundation for studying the dynamics of population structure through time. ### Competing Interest Statement The authors have declared no competing interest. National Human Genome Research Institute, https://ror.org/00baak391, R01HG014005
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vincentholst.bsky.social @vincentholst.bsky.social · 13/08/2026
In 2023, @nature.com published 'Papers and patents are becoming less disruptive over time', receiving world-wide media attention. Our Matters Arising, published after a 32 month delay (more on that soon), shows that the reported decline can largely be attributed to dataset artefacts. 🧵
The average CD_5 index per year for Web of Science. The original Park et al. decline (top curve) becomes essentially flat (bottom curve) when removing papers with CD_5=1. Those papers largely correspond to dataset artefacts.
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Graham Coop @gcbias.bsky.social · 12/08/2026
Excited for @gabrielesgarlata.bsky.social’s new preprint on the Genome-Wide Effect of Drift and Selection over a Single Generation 1/n www.biorxiv.org/content/10.6...
biorxiv.org
The Genome-Wide Effect of Drift and Selection over a Single Generation
The relative importance of genetic drift versus selection to evolutionary change has long been debated. This debate has mainly focused over long-time-scales (e.g. hundreds of thousands of generations)...
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Jonathan Pritchard @jkpritch.bsky.social · 12/08/2026
I'm curious about the reasons why some people/labs choose NOT to preprint their papers, either for specific papers or in general. Do you have a sense of this, either for yourself or for colleagues and collaborators? [I have some guesses, but curious to hear from others]
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Cedric Boeckx @cedricboeckx.bsky.social · 10/08/2026
Taking this opportunity to recommend once more @jkpritch.bsky.social’s excellent (and open-access!) textbook, which offers a very accessible introduction to the field of human genetics. 🧪🧬 web.stanford.edu/group/pritch...
web.stanford.edu
An Owner's Guide to the Human Genome
An Owner's Guide to the Human Genome
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Duncan Sproul @sproullab.bsky.social · 10/08/2026
Heartedly agree with this! Hugely useful to know numbers like these for biology in general not just genetics. Think my most used numbers are: ~6.6pg in a human cell ~145bp DNA wrapped round a nucleosome
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Aylwyn Scally @aylwyn-scally.bsky.social · 09/08/2026
Highly recommend this, and it's a key element in most physics training. I'd add another trick that many biologists could benefit from, a small thing that makes a big difference: always use units. If you're unsure about the units of your number, chances are you don't properly understand it.
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Jonathan Pritchard @jkpritch.bsky.social · 09/08/2026
Must-know numbers in human genetics -- As many of you know, I'm writing a free online textbook in human genetics. In this blog post I cover a key skill for genome scientists from that book: how to use mental math to figure out key genome properties. jkpritchard.substack.com/p/on-fermi-p...
jkpritchard.substack.com
On Fermi Problems in Human Genetics
and some very useful numbers about human genomes to get you started!
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Jonathan Pritchard @jkpritch.bsky.social · 09/08/2026
So, I've started a substack. I'll be writing about biology, but my first posts are about applying statistical methods to one of my hobbies: track fandom. In the first posts I describe the Pareto trade-off between a fast overall speed and finishing speed: jkpritchard.substack.com/p/greatest-1...
jkpritchard.substack.com
Greatest 1500m races? Fast times vs fast finishes, and the Pareto Frontier.
A statistical analysis of how overall race speed relates to finishing speed.
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Franck Polleux @franckp.bsky.social · 05/08/2026
I am exciting to highlight our new study published today in @cp-neuron.bsky.social. This work represents over 6 years of effort by an incredibly talented postdoc, Carlos Diaz-Salazar, in collaboration with @krzischlab.bsky.social, @bhadurilab.bsky.social at UCLA and Mercedes Paredes lab at UCSF 👇 🧵
cell.com
Human-specific SRGAP2 paralogs synchronize neotenic microglial maturation and synaptic development
Using a combination of microglia-specific conditional mouse knockout and knockin approaches and xenotransplantation of human iPSC-derived microglia, Diaz-Salazar et al. demonstrate that the human-spec...
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Jesse Engreitz @jengreitz.bsky.social · 04/08/2026
Update: scE2G is now online at Nature Genetics! Since the preprint, we added a new benchmark on a fully held-out CRISPR dataset. scE2G continues to show state-of-the-art performance, reinforcing that it generalizes well nature.com/articles/s41588-026-02695-8 1/
Held-out CRISPR benchmark: n=189 positives, 4,175 tested pairs from 5 cell types. Weighted AUPRC bar chart with scE2G-Multiome and scE2G-ATAC highest, above Distance to TSS, ABC, and 8 other single-cell methods.
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Julius Upmeier zu Belzen @juliusuzb.bsky.social · 05/08/2026
🧬 New preprint! An interpretable omnigenic neural network architecture for the human genome We introduce the Omnigenic Model (OGM), a neural network architecture for human genetics. It uses biological system structure to aggregate genetic variation for disease risk prediction.
doi.org
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Jeff Groh @jeffgroh.bsky.social · 28/07/2026
Avocados come in 2 varieties - A-types start each day female and switch to male midday. B-types do the reverse. In work just published from the last chapter of my PhD, we show this system evolved 40+million yrs ago and is regulated by alleles of 1 transcription factor www.pnas.org/doi/10.1073/...
pnas.org
Balanced polymorphism in a floral transcription factor underlies the ancient rhythm of daily sex alternation in avocado | PNAS
In avocado and certain wild relatives in Lauraceae, a highly synchronized daily rhythm of floral sex timing promotes cross-pollination between two ...
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Count Binface @countbinface.bsky.social · 27/07/2026
Here it is. My manifesto for the 2026 Clacton By-Election. It's a once-in-a-lifetime opportunity. Join me, clean up Clacton and let's make 13th August Bin Day! #VoteBinface #VoteyMcVoteface #YesWeTinCan
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Nicole Nova @nicole-nova.bsky.social · 23/07/2026
A fundamental question in disease ecology remains unresolved: How can an acute, immunizing virus persist in nature? Theory says viruses like measles need huge pools of susceptible hosts. Our new preprint offers an answer. www.biorxiv.org/content/10.6...
biorxiv.org
Persistent, Multi-Species Outbreaks and Long-Range Transmissions of a Measles-Like Virus
Canine distemper\---|a measles-like disease with high mortality and presently without a cure\---|poses a major threat to wild and domestic carnivores globally. Domestic dogs are generally considered t...
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Benoit Bruneau @benoitbruneau.bsky.social · 23/07/2026
4D Nucleome special issue of Science, featuring our paper "Dose-dependent sensitivity of human three-dimensional chromatin to a heart disease–linked transcription factor", led by Zoe Grant in my lab and Zhuzhen Kuang in Katie Pollard's lab @gladstoneinst.bsky.social www.science.org/toc/science/...
science.org
Contents | Science 393, 6809
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George Davey Smith @mendelrandom.bsky.social · 22/07/2026
Does the (live) shingles vaccine protect against dementia? Fergus Hamilton and colleagues provide important evidence in a new preprint using hospital data from the whole of England in a regression discontinuity design from which we *don't* show evidence of a meaningful protective effect /cont
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Andreas Gschwind @argschwind.bsky.social · 15/07/2026
Thrilled to share that our ENCODE enhancer–gene mapping paper is now out in Nature! An encyclopedia of human enhancer–gene regulatory interactions: www.nature.com/articles/s41... Thread 👇 1/
nature.com
An encyclopedia of human enhancer–gene regulatory interactions - Nature
An encyclopedia of more than 92 million enhancer–gene regulatory interactions created as part of the ENCODE4 project provides a valuable resource for future studies of gene regulation and human geneti...
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Jonathan Pritchard @jkpritch.bsky.social · 09/07/2026
It was a lot of fun working with @nikhilmilind.dev and @jeffspence.github.io on this paper about how gene dosage relates to traits (and resolving a nice paradox along the way). Thanks Craig Smail for a great Preview article!
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John Doench @johndoench.bsky.social · 06/07/2026
New preprint from the group, comparing CRISPRko and CRISPRi via a Perturb-seq readout: www.biorxiv.org/content/10.6...
biorxiv.org
Direct comparison of CRISPR knockout and interference with Perturb-seq
CRISPR knockout (CRISPRko) and CRISPR interference (CRISPRi) are two workhorse technologies for loss-of-function studies, yet direct comparisons between the two are scant relative to their widespread ...
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Jonathan Pritchard @jkpritch.bsky.social · 04/07/2026
really thinking FIFA missed a huge opportunity to schedule a 250th anniversary USA vs England rematch for today
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Shoa Clarke @shoaclarke.bsky.social · 02/07/2026
Really incredible work from the Tcheandjieu Lab that finally helps us to decipher what is going on at the 9p21 locus and its association with coronary disease on different ancestral backgrounds. www.cell.com/ajhg/fulltex...
cell.com
Linkage disequilibrium and allelic heterogeneity explain variation in coronary artery disease risk at 9p21 across populations and reduced effect in Africans
Using cross-ancestry fine-mapping across global and local ancestry groups, this study dissects the 9p21.3 coronary artery disease locus and shows how ancestry-specific haplotype structure shapes assoc...
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Anders Sejr Hansen @andersshansen.bsky.social · 29/06/2026
Very interesting new preprint from @jengreitz.bsky.social lab arguing that rather than there being significant enhancer-promoter compatibility, promoters simply differ in their enhancer responsiveness. If promoters are responsive, they respond to all enhancers. www.biorxiv.org/content/10.6...
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Nikhil Milind @nikhilmilind.dev · 22/06/2026
Super interesting work by @jonj-udd.bsky.social and @jeffspence.github.io is now out in Genetics!
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Jeff Spence @jeffspence.github.io · 22/06/2026
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...
doi.org
Allele Frequencies at Recessive Disease Genes are Mainly Determined by Pleiotropic Effects in Heterozygotes
Abstract. The classic theory of mutation-selection balance predicts the equilibrium frequency of genetic variation under negative selection. The model pred
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Anders Sejr Hansen @andersshansen.bsky.social · 22/06/2026
(1/n) Very excited to share tri-lab collab (Mirny & Zechner) led by Harvey, Henrik & Jack: Q: How do enhancers & promoters interact in space (contact vs. action-at-a-distance) and time (stable vs. transient)? A: Transient E-P contact (~25-42 nm lasting ~10-20 sec): www.biorxiv.org/content/10.6...
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American Statistical Association History of Statistics @hos-asa.bsky.social · 21/06/2026
Happy🎂to Siméon Poisson b #OTD 1781 (d 25 Apr 1840) His name is most associated with the Poisson distribution, developed to model jury decision-making. It gained traction in 1898 with Bortkiewicz’s analysis of Prussian horse kick data. But it is another example of Stigler’s Law of Eponomy 1/3
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Jase Gehring @skyjase.bsky.social · 17/06/2026
they even got the gradients right by pouring the H2O2 in from the side. it's a giga-plate fr @baym.lol is seeing his vision fully realized
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Michael Baym @baym.lol · 17/06/2026
I am SO VERY EXCITED for this
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Peter Andolfatto @pandolfatto.bsky.social · 16/06/2026
1/n Check out our new paper, spearheaded by @fborne.bsky.social, just out in PLoS Genetics doi.org/10.1371/jour....
doi.org
Epistasis among clustered lineage-specific amino acid substitutions in the Drosophila Trio protein
Author summary Proteins fold into three-dimensional structures that are essential for their function. Because these structures depend on interactions among amino acids, the fitness effect of a mutatio...
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Kamila Naxerova @naxerova.bsky.social · 16/06/2026
Please join us in NH (perfect place to be in August!) for this inspiring conference organized by @petrovadmitri.bsky.social and Joy Bergelson. Very interdisciplinary, so I look forward to learning tons of new concepts. www.grc.org/function-of-...
grc.org
Function of Evolving Systems - Gordon Research Conferences
GRC presents Function of Evolving Systems, a conference on .
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Daniel Bolnick @danielbolnick.bsky.social · 10/06/2026
A recently finished undergraduate (with lots of research time in my lab) applied for 60 research tech jobs with no luck... And this week I talked to an undergrad (son of a family friend) looking unsuccessfully for summer research in evolutionary genetics - AS A VOLUNTEER. (thread...)
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Molly Przeworski @mollyprz.bsky.social · 09/06/2026
Now published: journals.plos.org/plosbiology/...
journals.plos.org
What sets the mutation rate of a cell type in an animal species?
Mutation rates per generation are strikingly similar across germlines of animals and across at least one somatic cell type, suggesting a key role for natural selection in shaping mutation rates. This ...
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Yun Deng @yundeng.bsky.social · 09/06/2026
#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!
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Jonathan Pritchard @jkpritch.bsky.social · 04/06/2026
Massive dataset of perturbations+imaging from SF Biohub.
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Aaron Ragsdale @apragsdale.bsky.social · 03/06/2026
New from @gvbarroso.bsky.social in our lab: quantifying the relative importance of mutation rate variation and background selection to levels of diversity along the human genome.
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