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/

Jesse Engreitz@jengreitz.bsky.social · 2y ago

Introducing scE2G: a new model to link enhancers to target genes using single-cell data. Excited that scE2G will enable building enhancer maps in hundreds of cell types in the human body! Wonderful collaboration with @randersson.bsky.social @613weilin.bsky.social @mayayayas.bsky.social Thread👇

🧬 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.

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/...

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 ...

pnas.org

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

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...

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...

biorxiv.org

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/...

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

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/

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...

nature.com

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!

Jeff Spence@jeffspence.github.io · 4w ago

Craig Smail wrote up a really nice Preview of @nikhilmilind.dev's paper where we try to explain why large effect variants tend to affect traits in the same direction on average, which we think about in terms of the non-linearity of gene dosage response curves. www.cell.com/cell-genomic...

New preprint from the group, comparing CRISPRko and CRISPRi via a Perturb-seq readout: www.biorxiv.org/content/10.6...

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 ...

biorxiv.org

really thinking FIFA missed a huge opportunity to schedule a 250th anniversary USA vs England rematch for today

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...

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...

cell.com

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...

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

Jeff Spence@jeffspence.github.io · last mo.

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...

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...

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

doi.org

(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...

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

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

Harmit Singh Malik@harmitmalik.bsky.social · 2mo ago

One of the world's most tightly controlled experimental evolution projects is underway in DC, and I hope someone has had the foresight to collect a time series of algal samples. www.cnn.com/2026/06/16/p...

I am SO VERY EXCITED for this

Harmit Singh Malik@harmitmalik.bsky.social · 2mo ago

One of the world's most tightly controlled experimental evolution projects is underway in DC, and I hope someone has had the foresight to collect a time series of algal samples. www.cnn.com/2026/06/16/p...

1/n Check out our new paper, spearheaded by @fborne.bsky.social, just out in PLoS Genetics doi.org/10.1371/jour....

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...

doi.org

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-...

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...)

Now published: journals.plos.org/plosbiology/...

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 ...

journals.plos.org

Molly Przeworski@mollyprz.bsky.social · 8mo ago

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

#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!

Massive dataset of perturbations+imaging from SF Biohub.

#SingleCell preprints@prepub-singlecell.bsky.social · 2mo ago

A multimodal perturbation atlas defines the phenotypic resolution of cellular morphology. #SingleCell 🧪🧬🖥️ https://www.biorxiv.org/content/10.64898/2026.06.01.728087v1

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.

bioRxiv Evolutionary Biology@biorxiv-evobio.bsky.social · 2mo ago

Causal inference clarifies the roles of background selection and mutation rate variation in shaping human genetic diversity https://www.biorxiv.org/content/10.64898/2026.06.02.727906v1

We took ~750,000 whole genomes and found the putative mechanism by which mitochondrial DNA mutations accumulate with age in blood. Spoiler: we think these mutations arise by replication error and tag age-related clonal hematopoiesis. Read @nature.com broad.io/ob2jft

Mechanism of age-related accumulation of mtDNA mutations in human blood - Nature

Genome-wide analyses indicate that accumulation of mitochondrial DNA mutations, a hallmark of ageing, may be caused by cryptic replication errors, which act as passenger mutations that eventually become detectable with age owing to age-related somatic mosaicism, rather than oxidative damage.

broad.io

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.

Romain Lopez@biologicalml.org · 2mo ago

🚀 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...

I’m looking to hire one or two postdocs - possible projects include pop gen theory, methods development, and human evolutionary inference. Please share, and email if you are interested. More info: evoldir.net/brian/evoldi...

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.