How can we hope to understand organismal development when it is controlled by huge, complex networks of interacting genes?


One option is to move away from molecular details and focus on learning representations and rules.

Check out the new perspective from me and @jamesbriscoe.bsky.social

Gene regulatory networks: from correlative models to causal explanations Nature Reviews Genetics - In this Perspective, Maizels and Briscoe discuss the limitations of current models of gene regulatory networks and outline solutions to harness data abundance without...

New Perspective form Rory Maizels & me: "Gene regulatory networks: from correlative models to causal explanations"

Gene regulatory networks are supposed to give us mechanistic explanations of development, so why are we drowning in 'hairballs' of statistical correlations?

rdcu.be/e7zx7

Gene regulatory networks: from correlative models to causal explanations Nature Reviews Genetics, Published online: 09 March 2026; doi:10.1038/s41576-026-00939-1In this Perspective, Maizels and Briscoe discuss the limitations of current models of gene regulatory networks and outline solutions to harness data abundance without compromising explanatory power.

New online! Gene regulatory networks: from correlative models to causal explanations

We are thrilled to share our new pre-print: “System-wide extraction of cis-regulatory rules from sequence-to-function models in human neural development”. S2F-deeplearning models can accurately encode enhancers, yet decoding these models into human-interpretable rules remains a major challenge.

🧪 The #IRBBarcelona #PhD Call is still open! We are offering PhD #fellowships to talented young scientists from around the world who wish to pursue a doctoral degree in #biomedicine!

Learn more and apply by January 9!

General call ➡️ https://bit.ly/3LtzIXi
IRB DRIVE call ➡️ https://bit.ly/4hODx5B

TAD boundary architecture and gene activity are uncoupled Topologically associating domains (TADs) are prominent features of genome organization. A proposed function of TADs is to contribute to gene regulation by promoting chromatin interactions within a TAD...

"We find that while TAD boundaries pair more frequently than non-boundary regions, these interactions are infrequent and are uncorrelated with transcriptional activity of genes within the TAD. (...) These results suggest that TAD boundary architecture and gene activity are largely uncoupled"

A genome-scale single-cell CRISPRi map of trans gene regulation across human pluripotent stem cell lines Feng et al. present the first genome-scale CRISPR interference perturbation map with scRNA-seq readout across many genetic backgrounds in human pluripotent cells, pioneering population-scale CRISPR pe...

Happy to see this out now in Cell Genomics: A genome-scale single-cell CRISPRi map of trans gene regulation across human pluripotent stem cell lines: www.cell.com/cell-genomic...

Virtual Cell Perturbation Metrics Reloaded Thoughts on metrics for perturbation prediction models

As more single-cell perturbation data become available, it is crucial to establish a consensus on measures of success for perturbation prediction models.

I reviewed recent literature and collected some thoughts on the current state of affairs.

open.substack.com/pub/giovanni...

Comic. Panels up to the 10-year point are grayed out. New panels since the Ten Years comic, which chronicles the first ten years of PERSON 1's journey with cancer: (1) [two people in bed] PERSON 1 (woman): One more chapter? PERSON 2 (man): Don’t we both have to get up early? PERSON 1: Nnnnnggggh PERSON 2: Sure, good point. (2) [many people wearing masks, walking while looking at graphs on their phones] (3) [birds landing on people] PERSON 2 in beanie and scarf: Hah! They like *my* seeds best. PERSON 1 in scarf holding phone with a bird sitting on it: Wait, how do I take a picture of this one? (4) [two people rowing boats with tree landscape] (5) [Person 1 carries overflowing stack of things to Person 2 in bed] PERSON 1: I brought you honey lemon tea, more pillows, a cinnamon roll, Tylenol, another blanket, a– PERSON 2: It was just Appendicitis, I’m really– PERSON 1: *It is my turn to take care of you and I am going to do it right!* (6) [Two people in car] (7) [still in car) PERSON 1: Oh my god. PERSON 2: Oh my god. (8) [car driving] PERSON 1: Pull over! PERSON 2: I am! (9) [both people get out of car] (10) [Large colored panel of aurora borealis over water with both people looking on] (11) [Person 1 sits against tree while Person 2 lies on the ground] PERSON 1: Fifteen years. No sign of the cancer. (12) I *am* having some weird symptoms. Joint pain. Fatigue. I think I’m losing my close-up vision. PERSON 2: Yeah. Me too. (13) PERSON 2: I think we’re getting old. (14) PERSON 1: I guess that’s okay. PERSON 2: It’s all I wanted.

Fifteen Years

xkcd.com/3172/

We wrapped up an inspiring week with a visit to NVIDIA headquarters right after the scverse conference. Huge thanks to the NVIDIA Healthcare team and @severin7.bsky.social for hosting us and for the great discussions on scaling single-cell analysis and accelerating open science ⚡️

An illustration of a cross-section of a tree trunk, highlighting the core labeled "Undead wood" and a glowing ring-shaped layer labeled "Alive part".

Trees are amazing! They build their bodies from thin air, move water with pressures that would crush a human, and grow using a system of living cables wrapped in layers of corpses. Watch our video to find out how they work, and why they might even be immortal: https://kgs.link/TreesAreDead

I'm guest-editing a collection on "Enhancer-promoter interactions" at Genome Biology. Please send us your exciting stories!

link.springer.com/collections/...

📍 Latest OmniPath paper is out now! ➡️ academic.oup.com/nar/advance-...

All scverse attendees

scverse conference organizers

First session

scverse conference 2025 done ✅ Really engaging week at Stanford with scPerturb-seq work, agentic models in biology, and strong interest in scaling software to millions of cells. Organizing alongside the rest of the @scverse.bsky.social team was a blast! Hope attendees found it productive 😄

A highlight of my summer was this collab w/
@twangmdphd.bsky.social ! CRISPR base editors are driving several clinical trials, but it's hard to quantify off-target edits and their effects. Tong developed a sequencing assay to identify off-targets *in primary cells* 🧬🖥️🧪 #genomics #chromatin #CRISPR

Can't make it to Stanford? We've just opened remote attendance for scverse Conference 2025! Join us online Nov 17-18 via Zoom 👇

Nature suggests you use their "Manuscript Adviser" bot to get advice before submitting

I uploaded the classic Watson & Crick paper about DNA structure, and the Adviser had this to say about one of the greatest paper endings of the century:

Benchmarking large language models for personalized, biomarker-based health intervention recommendations npj Digital Medicine - Benchmarking large language models for personalized, biomarker-based health intervention recommendations

How do we know whether our AI solutions are up to our standards, for instance in clinical recommendations? We try to contribute to the answer by our recent study on *Benchmarking large language models for personalized, biomarker-based health intervention recommendations* rdcu.be/eMVeL

Congrats Britta! 🎉

Arc is looking for an outstanding early-career scientist to be our next Science Fellow. This program provides resources and freedom for those looking to transition into a principal investigator role immediately after doctoral training. Apply here: arcinstitute.org/programs/sea...

Which mutations rewire function of regulatory DNA?

Excited to share SEAM: Systematic Explanation of Attribtuion-based Mechanisms. SEAM is an explainable AI method that dissects cis-regulatory mechanisms learned by seq2fun genomic deep learning models.

Led by @EESetiz

1/N 🧵👇

🌟 Thank You to Our Gold Sponsor: Stellaromics! 🌟

We're proud to recognize Stellaromics as a Gold Sponsor of scverse conference 2025! 🥇

@stellaromics.bsky.social
#scverse2025 #SpatialBiology #3DSpatial #ComputationalBiology #SingleCell #Stellaromics #SpatialOmics #Bioinformatics

Now that I'm settled in at @umasschan.bsky.social, I'm hiring at all levels: grad students, post-docs, and software engineers/bioinformaticians!

The goal of my lab is to understand the regulatory role of every nucleotide in our genomes and how this changes across every cell in our bodies.

Loops of DNA Equipped Ancient Life To Become Complex | Quanta Magazine New work shows that physical folding of the genome to control genes located far away may have been an early evolutionary development.

I adored writing this piece. It brings together several of the things preoccupying me right now, like chromatin organization and gene regulation. There's so much more to be said on that. Also, these marine critters look gorgeous.
www.quantamagazine.org/loops-of-dna...

🧠 Arc Workshop at the upcoming scverse conference 2025 🧠

Processing and Modeling Large-Scale Single-Cell Perturbation Data with Machine Learning
🧵

@arcinstitute.org

#scverse2025 #PerturbSeq #MachineLearning #SingleCell #CRISPR #GenomicScreening #VirtualCells

"… Goodall’s … is a story of genuine scientific curiosity, determination, and respect for nature and humanity …" H. Holden Thorp, Editor-in-chief, Science journals

Jane Goodall has died at the age of 91.

In 2020, Goodall spoke with Science Editor-in-Chief H. Holden Thorp for a #ScienceEditorial reflecting on the 60th anniversary of her arrival in Gombe to study wild chimpanzees. Read more: https://scim.ag/472Chb8

Introducing ParTIpy, a python package for Pareto Task Inference that scales to large-scale datasets, including single-cell and spatial transcriptomics.
🔗 Manuscript: www.biorxiv.org/content/10.1...
💻 Code: partipy.readthedocs.io

My favorite part of last-year #scverse conference was to finally meet in-person many developers that I only knew from their GitHub username!

Submissions and travel grant applications close in 3 days. Find out more and apply at scverse.org/conference2025

@scverse.bsky.social

A-tack-seq OR attack-seq?

Explain your answer.

Been digging through GEO for multiome single-cell data, frustrating how much is unusable 🫠 (missing annotations, frag files, raw data). Uploading properly takes effort, but it makes your dataset so much more impactful... Props to (most of) the authors who fixed things when I reached out, though 👍