Practical utility of sequence-to-omics models for improving the reproducibility of genetic fine-mapping https://www.biorxiv.org/content/10.64898/2026.02.04.703796v1

Yesterday, five-year-old Liam and his dad Adrian were released from Dilley detention center. I picked them up last night and escorted them back to Minnesota this morning. Liam is now home. With his hat and his backpack.

We mapped the fitness landscape of the 10kb MYC locus using SpRY-Cas9 saturation mutagenesis. 67% of the essential bps are noncoding. So even for a protein coding gene locus, most genetic information may be encoded outside of coding regions.

Does the noncoding genome actually carry more genetic information than coding seqs? Motivated by this question we mutated every bp in the 10kb MYC locus. Results are even more exciting: Decoding the MYC locus reveals a druggable ultraconserved RNA element www.biorxiv.org/content/10.6...

Today in @nature.com, we describe how discarded reads in biobank-scale WGS can help resolve the genetic predictors and consequences of Epstein-Barr Virus (EBV) infection. Wonderful working with @ryandhindsa.bsky.social @sherrynyeo.bsky.social @erinmayc.bsky.social www.nature.com/articles/s41...

AlphaGenome is out in @nature.com today along with model weights! 🧬 📄 Paper: www.nature.com/articles/s41... 💻 Weights: github.com/google-deepm... Getting here wasn’t a straight path. We discussed the story behind the model, paper & API in the following roundtable: youtu.be/V8lhUqKqzUc

An NIH source tells me that after this story was published, agency leadership held an emergency meeting about Council approval and is looking for ways to speed up the pipeline. "Better late than never?" the source says.

ICE has detained at least 3,800 kids under the second Trump administration — more than 500 of whom were under 5 years old. Children shouldn't be locked up by our government.

"Senate Democrats will not provide the votes to proceed to the appropriations bill if the DHS funding bill is included,” Schumer said Saturday evening. talkingpointsmemo.com/news/democra...

Nature research paper: Construction of complex and diverse DNA sequences using DNA three-way junctions go.nature.com/4qu2ExZ

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.

Excited to share our latest work in @ajhgnews.bsky.social 🧬📄 We mapped the regulatory landscape of human liver at single-nucleus resolution using snMultiome, connecting genetic variants to the cell-type mechanisms underlying cardiometabolic disease. www.sciencedirect.com/science/arti...

The conference (agreement between House and Senate) appropriations bill that includes HHS and NIH was released this morning. www.appropriations.senate.gov/news/majorit... 1/5

How can we identify circRNAs that might be functional? Together with @jengreitz.bsky.social, Howard Chang, and team, we found that answering this question is much more challenging than previously thought! academic.oup.com/nar/article/... See thread below:

The @zeitlingerlab.bsky.social is pleased to announce @sergio-gma91.bsky.social’s preprint “High-resolution binding data of TFIID and cofactors show promoter-specific differences in vivo” (www.biorxiv.org/content/10.6...). TLDR; TFIID behaves differently depending on promoter type. More below:

Thinking about using Cas13 to screen for functional circRNAs? Think again! Thread coming soon

How well does TWAS estimate a gene’s direction of effect on a trait? We think of this as an important stress-test for the accuracy of TWAS. In a new pre-print, we find that TWAS gets the sign wrong around 20-30% of the time! doi.org/10.64898/202... 1/n

Together with @ronghuizhu.bsky.social, we are thrilled to present our new perturb-seq study of 22M primary CD4+ T cells, across donors and timepoints – the result of a decade-long collaboration between the Marson @marsonlab.bsky.social and Pritchard @jkpritch.bsky.social labs 🧵 tinyurl.com/gwt2025

Join @stirlingchurchman.bsky.social, @moffittlab.bsky.social, @saramostafavi.bsky.social, me and all speakers for the 2026 CSHL meeting Systems Biology: Global Regulation of Gene Expression, March 11-14. Abstract deadline January 9! More infos and registration at meetings.cshl.edu/meetings.asp...

A free, open-access library of high-quality organism illustrations for science communication

Do transcriptional activators work on any promoter? Our data says no. 🙅‍♂️ Despite driving ~2/3 of mammalian genes, CpG island (CGI) promoters have remained a puzzle. We identified >50 activators that are exclusively compatible with this promoter class. 🧬

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits https://www.biorxiv.org/content/10.64898/2025.12.23.696273v1

We’re excited to share our new Nature Genetics paper examining the genetic architecture of aortic valve function and aortic stenosis. We used deep learning of cardiac MRI and MTAG to study disease biology long before clinical diagnosis. nature.com/articles/s41... 1/10

A reminder to use the right P2A sequence to produce separate proteins - the images are from a GPCR-P2A-mCherry construct using a P2A variant without (upper row) and with (lower row) a preceding GSG linker.

GWAS has been an incredible discovery tool for human genetics: it regularly identifies *causal* links from 1000s of SNPs to any given trait. But mechanistic interpretation is usually difficult. Our latest work on causal models for this is out yesterday: www.nature.com/articles/s41... A short🧵:

The new Enabling Discovery through GEnomics (EDGE) Program page is posted. Please contact us at [email protected] if you have questions. www.nsf.gov/funding/oppo...

The Court wrote a roadmap for illegal gerrymanders: Just wait to pass them until the “eve” of the election, and no one can stop you.

Oh hey, looks like I can upload longer videos here now! Here’s my most recent one covering the latest findings on ecDNA retention mechanisms from the Chang & Mischel labs.

Excited to share our new FinnGen single-nucleus multiome preprint! 🧬 We profiled ~10M PBMCs (snRNA-seq + snATAC-seq) from 1,108 Finnish donors to map how genetic variants drive complex disease through chromatin and gene regulation 🧵👇 🔗 Link: www.medrxiv.org/content/10.1...

We are thrilled to announce the first official release (v0.1.8) of #𝗯𝗲𝗱𝗱𝗲𝗿, the successor to one of our flagship tool, #𝗯𝗲𝗱𝘁𝗼𝗼𝗹𝘀! Based on ideas we conceived of long ago (!), this was achieved thanks to the dedication of Brent Pedersen. 1/n

Massive single-cell study by Kanai et al (www.medrxiv.org/content/10.1...): - Once statistical power is high, constrained genes have more (though weaker) eQTLs. - Chromatin-QTLs near constrained genes have "normal" effect sizes, colocalize more with disease, but exhibit attenuated peak-gene effects.

📣 I hereby make my Bluesky debut to announce that our work linking DNA binding affinities and kinetics 𝘪𝘯 𝘷𝘪𝘵𝘳𝘰 and 𝘪𝘯 𝘷𝘪𝘷𝘰 for the human transcription factor KLF1 just got published in Cell! @cp-cell.bsky.social www.cell.com/cell/fulltex... Key findings in a thread (1/6):

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

Design and interpretation of eQTL-GWAS colocalisation studies: lessons from a large-scale evaluation https://www.medrxiv.org/content/10.1101/2025.11.20.25340664v1

The architecture of allele-specific regulatory variant effects across five human genomes https://www.biorxiv.org/content/10.1101/2025.11.22.689315v1

New paper “Proteome-wide model for human disease genetics” is now live at Nature Genetics: rdcu.be/eRu7K popEVE (pop.evemodel.org) finds the needles in the haystacks of human genetic variation:

Excited to share a preprint of my PhD project looking at interactions between SNPs and polygenic scores in the UK Biobank! A thread... 🧵 www.medrxiv.org/content/10.1...

In August, NIH institute and center directors received this document entitled "Achieving NIH Mission: Leveraging Funding Policies". 1/6

We are pleased to announce a new preprint by @mlweilert.bsky.social: “Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs” (www.biorxiv.org/content/10.1...). See summary and longer recap below: (TLDR; low-affinity motifs matter as pioneers!)

First time on Bsky and first big announcement! I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature. Our manuscript is here: www.nature.com/articles/s41....

Excited to share Nona: a unifying multimodal masking framework for functional genomics. Models for DNA have evolved along separate paths: sequence-to-function (AlphaGenome), language models (Evo2), and generative models (DDSM). Can these be unified under a single paradigm? 1/15

A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording - @jshendure.bsky.social @troymcdiarmid.bsky.social @uwgenome.bsky.social go.nature.com/49eTPCu

How do GWAS and rare variant burden tests rank gene signals? In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck! 🧬🧪🧵 www.nature.com/articles/s41...

Our latest paper has just been published in Cell! doi.org/10.1016/j.ce... We developed a new method called MCC ultra, which allows 3D chromatin structure to be visualised with a 1 base pair pixel size.

Stoked to share our latest work entitled: “Large-scale discovery of neural enhancers for cis-regulation therapies” shorturl.at/H3Qww This is an enormous team effort that I had the honour of spearheading with Nick Page and Florence Chardon. Bluetorial below.

I'm happy to share that our gReLU package is now published in Nature Methods! www.nature.com/articles/s41...

Today my @nytimes.com colleagues and I are launching a new series called Lost Science. We interview US scientists who can no longer discover something new about our world, thanks to this year‘s cuts. Here is my first interview with a scientist who studied bees and fires. Gift link: nyti.ms/3IWXbiE

i desperately want everyone involved in the destruction of USAID to have to, st the very least, answer to the american people for the suffering and misery they have caused apnews.com/article/myan...

🧵1/ Excited to share our new paper introducing a new #singlecell assay: scTF-seq, a high-throughput single-cell approach to explore how transcription factor (TF) dose shapes cell identity and reprogramming outcomes. 🔗 www.nature.com/articles/s41... Big congrats to the entire team @EPFL & @SIAT_China

Many enhancers that drive tissue-specific gene expression are already connected to gene promoters in human pluripotent cells. In a new preprint, we share some clues about when, how, and why this happens! www.biorxiv.org/content/10.1...