James Opzoomer

New preprint on technologies to scale up CRISPR screens.

We use them to map 665,856 pairwise genetic perturbations and outline a path to comprehensive interaction mapping in human cells.

We also introduce an approach for cloning lentiviral libraries with billions of elements.

TF-MINDI is out! A new method to learn cis-regulatory codes through rich embeddings of TF binding sites. TF-MINDI decomposes motif neighbourhoods, and works downstream of any sequence-to-function deep learning model. We deeply study the enhancer code in human neural development, check out the thread

Ok here it is - out of 44 FDA approvals this year, 31 are small molecules (70%), 26 of those are oral drugs (84%), 22 of them are chiral (71%). This is the largest number and percentage of chiral FDA approved molecules in a single year. Fitusiran is not a small molecule, bonus.

My thoughts on the matter: www.nature.com/articles/s41...

Looking for some Thanksgiving reading? 🦃🦃🦃

🚨Check out our new preprint on CRISPore-seq!🚨

Combining pooled CRISPR perturbations with single-cell sequencing has been tremendously powerful... but we are missing a lot with current approaches like Perturb-seq and ECCITE-seq.

Universal consensus 3D segmentation of cells from 2D segmented stacks - Nature Methods u-Segment3D is a universal framework that translates and enhances 2D instance segmentations to a 3D consensus instance segmentation without training data. It performs well across diverse datasets, inc...

u-Segment3D: a universal framework for 2D to 3D cell segmentation that generalizes across cell types and imaging modalities.

www.nature.com/articles/s41...

The Tiling Tree Method, Part 2: Common Pitfalls and How to Overcome Them How to really think of every way of solving a problem

Just posted, "The Tiling Tree Method, Part 2: Common Pitfalls and How to Overcome Them" a follow-up to our previous essay on the "tiling tree" method for thinking of all the possible solutions to a problem, by Claire Wang, Nina Khera, and myself. engineeringx.substack.com/p/the-tiling...

CRISPR live-cell imaging reveals chromatin dynamics and enhancer interactions at multiple non-repetitive loci - Nature Biotechnology Multiplexed DNA imaging uncovers promoter−enhancer interaction dynamics and effects of epigenetic modifications.

CRISPR live-cell imaging reveals chromatin dynamics and enhancer interactions at multiple non-repetitive loci
www.nature.com/articles/s41...

Are you using any of our factor models, such as MOFA? 🛵
You might’ve found it challenging to tailor them to your specific use cases - not anymore!

Introducing MOFA-FLEX: a flexible, modular factor analysis framework designed for customizable modeling across diverse multi-omics data scenarios. 1/n

Squidiff: predicting cellular development and responses to perturbations using a diffusion model - Nature Methods Squidiff is a diffusion-based model to predict transcriptomic changes in response to perturbations.

Squidiff: a diffusion-based model to predict transcriptome response to perturbations.

www.nature.com/articles/s41...

TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1+ macrophages - Nature Genetics Targeting TGFBR1 in transplantable mouse colorectal tumor organoids improves response to anti-PD-L1 therapy. Mechanistically, TGF-β abrogates clonal expansion of T effector and memory phenotypes and i...

1/17 🧵
🙌Thrilled to share our first hard-core immunology paper out today in Nature Genetics! 👇

➡️We unravel how TGFβ suppresses the innate and adaptive immune system in microsatellite stable colorectal cancer (MSS CRC).

Very proud of the team and efforts behind it.

www.nature.com/articles/s41...

Enabling options for review: from training and transparency to author-centered AI tools - openRxiv Peer review is widely viewed as a critical aspect of biomedical communication. Ideally, it provides authors with feedback so they can improve manuscripts and gives readers, particularly nonspecialists...

Excited to launch an openRxiv partnership with the scientist-run AI review service qed (@qedscience.bsky.social), the brainchild of @odedrechavi.bsky.social 1/n

openrxiv.org/enabling-rev...

BioContextAI is a community hub for agentic biomedical systems - Nature Biotechnology Nature Biotechnology - BioContextAI is a community hub for agentic biomedical systems

BioContextAI is a community hub for agentic biomedical systems - @puellesv.bsky.social @biocontext.ai go.nature.com/3JmqKux

ESPRESSO: spatiotemporal omics based on organelle phenotyping - Nature Methods ESPRESSO leverages functional information obtained from organelles for deep spatiotemporal phenotyping of single cells.

ESPRESSO: a method that extracts functional information about organelles for deep spatiotemporal phenotyping at the single cell level.

www.nature.com/articles/s41...

Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database - Nature Communications Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD),…

New study of 800K+ genomes from gnomAD reveals most “pathogenic” variants in healthy people aren’t truly disease-tolerant. They are explained by annotation errors, mosaicism, or compensatory variants. 🧬
A big step for precision medicine!
www.nature.com/articles/s41...

Programming human cell type-specific gene expression via an atlas of AI-designed enhancers Differentially active enhancers are key drivers of cell type specific gene expression. Active enhancers are found in open chromatin, which can be mapped at genome scale across tissue and cell types. T...

🚀Excited to share our new preprint: “Programming human cell type-specific gene expression via an atlas of AI-designed enhancers”

We built the largest repository of AI-designed enhancers, validated across 10 human cell lines + mouse retina.

👉 www.biorxiv.org/content/10.1...

#AI #Genomics #SynBio

Age and gender distortion in online media and large language models - Nature Stereotypes of age-related gender bias are socially distorted, as evidenced by the age gap in the representations of women and men across various media and algorithms, despite no systematic age differ...

When ChatGPT was asked to rate 40,000 résumés, it ranked the older male candidates as better quality than the younger female applicants.

Scientists no Longer Find Twitter Professionally Useful, and have Switched to Bluesky Synopsis. Social media has become widely used by the scientific community for a variety of professional uses, including networking and public outreach. For

Looks like the science community has found a home.
academic.oup.com/icb/article-...

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

Cryo-mtscATAC-seq for single-cell mitochondrial DNA genotyping and clonal tracing in archived human tissues High-throughput clonal tracing of primary human samples relies on naturally occurring barcodes, such as somatic mitochondrial DNA (mtDNA) mutations detected via single-cell ATAC-seq (mtscATAC-seq). Fr...

🚨 New preprints from our lab!
First, we introduce Cryo-mtscATAC-seq, led by Maren (@ms-maren.bsky.social ), enabling high-throughput clonal tracing from frozen human samples by isolating nuclei with their mitochondria (“CryoCells”).
👉 www.biorxiv.org/content/10.1...

We are excited to share GPN-Star, a cost-effective, biologically grounded genomic language modeling framework that achieves state-of-the-art performance across a wide range of variant effect prediction tasks relevant to human genetics.
www.biorxiv.org/content/10.1...
(1/n)

A fascinating and important read!

🚨 New preprint

We present an extended version of ScAPE, the method that won one of the prizes 🏆 in the @neuripsconf.bsky.social 2023 Single-Cell Perturbation Prediction challenge.

📄 preprint: doi.org/10.1101/2025...
🧬 code: github.com/scapeML/scape

Review | The inventor of the web says we can recapture its magic. Is he right? In “This Is for Everyone,” Tim Berners-Lee writes about the early days of the internet and how we might restore its more democratic roots.

“The free, open access communications paradigm we have did not arrive like magic. It was the product of a fair amount of political wrangling” - that's why we must continue our fight for the web.

🙏 @washingtonpost.com for reviewing 'This Is for Everyone'

www.washingtonpost.com/books/2025/0...

Nick Clegg and Tim Berners-Lee: the battle for the soul o... The ex-deputy PM toes the line of his former Meta paymasters, while the web's inventor shares his vision of a utopian digital future

Thank you to @observeruk.bsky.social for this thoughtful review.

“Berners-Lee is clear-eyed about the benefits and the dangers. This Is for Everyone contains some very sharp thinking about what we need to do now.”

We must fight for the web we want.

observer.co.uk/culture/book...

Just published: The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube

A global temporal chromatin program, operating across the CNS, directs binding of specific spatial TFs & hence when/where neurons & glia are born

authors.elsevier.com/sd/article/S...

In vivo mapping of mutagenesis sensitivity of human enhancers - Nature Human enhancers contain a high density of sequence features that are required for their normal in vivo function.

In vivo mapping of mutagenesis sensitivity of human enhancers

www.nature.com/articles/s41...

Cryptic genetic variation shapes the fate of gene duplicates in a protein interaction network - Nature Communications Over time, paralogous genes accumulate changes in their sequences that do not affect their function, which is called cryptic variation. Using paralogous myosins, this study shows how cryptic variation...

How does cryptic genetic variation influence the long-term fate of gene duplicates (paralogs)?
Our new study addresses this question by dissecting the evolutionary potential of redundant myosin paralogs in yeast nature.com/articles/s41... (1/12)

We're thrilled to introduce PromoterAI — a tool for accurately identifying promoter variants that impact gene expression. 🧵 (1/)

Dynamic Landscape Analysis of Cell Fate Decisions: Predictive Models of Neural Development From Single-Cell Data Building a mechanistic understanding of cell fate decisions remains a fundamental goal of developmental biology, with implications for stem cell therapies, regenerative medicine and understanding dise...

Our latest "Dynamic Landscape Analysis of Cell Fate Decisions: Predictive Models of Neural Development From Single-Cell Data"

A rigorous mathematical foundation for Waddington's landscape to study cell fate decision making

Applied to ventral neural tube development

www.biorxiv.org/content/10.1...