How do genetic variants affect secreted proteins? A new study introduces MultiSTEP, a scalable method for measuring variant effects in coagulation factor IX. The approach assessed >8,500 F9 missense variants and helped reclassify 63.1% of VUSs. pubmed.ncbi.nlm.nih.gov/40514537/

Multiplex and multimodal mapping of variant effects in secreted proteins via MultiSTEP - PubMed

Despite widespread advances in DNA sequencing, the functional consequences of most genetic variants remain poorly understood. Multiplexed assays of variant effect can measure the function of variants at scale but cannot readily be applied to the ~10% of human genes encoding secreted proteins. Here w …

pubmed.ncbi.nlm.nih.gov

A massive update: At least ~15 companies~ are selling scientists antibodies using faked validation data. We've documented 18,000+ manipulated images on 17,000+ products sold by leading laboratory suppliers including Thermo Fisher, Abcam, Santa Cruz Biotechnology, Millipore Sigma and Bio-Techne. 1/🧵

First synthetic mouse enhancers active in defined embryonic tissues! Great collaboration led by @alex-stark.bsky.social lab now at @natgenet.nature.com

Shenzhi Chen@shenzhichen1999.bsky.social · last mo.

Excited to share our paper in @natgenet.nature.com on the de novo design of tissue-specific mammalian enhancers that function in vivo in mouse embryos. 🧬🐭 www.nature.com/articles/s41...

Latest from our lab! A proteome-wide association study of cardiovascular diseases in 640,000 participants of multiple ancestries www.medrxiv.org/content/10.6... A truly global collaboration of computational and experimental researchers. h\t @yuxu.bsky.social, Doug Loesch, Henry Taylor among many!

Finally… Excited to share what I’ve been working on for the first half of my PhD! ENCODE GRAMMAR: One of the largest collections of regulatory DNA seq2func models to date (3,865 in total) trained across ENCODE, with full model interpretations and annotations tracks. Blog: tinyurl.com/3hmknhaa 1/

Thrilled to share that our scE2G paper is now published in Nature Genetics! www.nature.com/articles/s41... scE2G predicts enhancer-gene regulatory interactions from single-cell data with state-of-the-art performance. Amazing work led by @mayayayas.bsky.social and @613weilin.bsky.social!

Mapping enhancer–gene regulatory interactions from single-cell data - Nature Genetics

scE2G is a family of models that predict enhancer–gene regulatory interactions from single-cell datasets and enable mapping of these interactions across diverse cell types and tissues.

nature.com

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

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/

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👇

RNA-seq tells us how much RNA is present in the cell. But to understand gene regulation, we need to easily measure the synthesis and decay rates driving this abundance. We introduce AIR-seq: analog intrinsic recoding sequencing. (1/6) www.biorxiv.org/content/10.6...

Analog intrinsic recoding measures RNA dynamics without chemical conversion

Steady-state RNA abundance measurements mask the synthesis and decay rates that shape gene expression. Analog intrinsic recoding sequencing (AIR-seq) repurposes the base-pairing properties of N4-hydro...

biorxiv.org

super excited to share that I'm starting as an Assistant Professor at CU Denver this fall! my lab will be right in the heart of downtown Denver :) mattioli-lab.org i'm hiring! if you're interested in joining us to study how alternative isoforms contribute to cancer, please reach out

A massive team effort with @kmualim.bsky.social , @karbalayghareh.bsky.social, @mayayayas.bsky.social , @kanishkadey.bsky.social, Evelyn Jagoda, Ramil Nurtdinov, Wang Xi, Lars Steinmetz, @anshulkundaje.bsky.social , @jengreitz.bsky.social and many others across ENCODE. 6+ years in the making! 2/

An encyclopedia of enhancer-gene regulatory interactions — online today! nature.com/articles/s4158… Now with an improved model, expanded maps across 1400+ biosamples, larger validation CRISPR datasets, and guidance on applying the model 1/

Andreas Gschwind@argschwind.bsky.social · 3mo ago

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/

We believe the models, benchmarks and E–G maps will provide a lasting resource. Predictions for 1,458 biosamples: www.encodeproject.org Model: github.com/EngreitzLab/ENCODE_rE2G Benchmarking pipelines: github.com/EngreitzLab/... github.com/EngreitzLab/... github.com/Deylab999MSK... 16/

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

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

A biology journal trialled paying their reviewers and found it led to faster first editorial decisions – and increased review quality. go.nature.com/446SaLu

Why paying peer reviewers works, according to a journal’s editor-in-chief

A biology journal which paid peer reviewers found that the approach cut the time to a first editorial decision by 85% and maintained high-quality reviews.

go.nature.com

Our evil ORFeome paper is out! In collaboration with @alex-stark.bsky.social, we screened ~4,000 viral proteins and secreted effectors from bacteria and parasites, covering hundreds of diverse pathogens, for phenotypes in human cells.

We find that promoters differ dramatically in their intrinsic capacity to be activated by *any* enhancer (>100-fold vs 1.1-fold) -- from highly- to effectively non-activatable! Promoter responsiveness scales the magnitude of activation while enhancer rank-order stays similar.

Does every enhancer work with every promoter? With @jengreitz.bsky.social and Will Greenleaf, we revisit this long-debated question and resolve an outstanding contradiction in the field. A tour 🧵👇 www.biorxiv.org/content/10.6...

Intrinsic promoter responsiveness dictates sensitivity to transcriptional activation by enhancers

Enhancers activate specific target promoters, but whether intrinsic enhancer-promoter compatibility contributes to this specificity is debated. Recent studies using different reporter assays have reac...

biorxiv.org

New preprint! 📢 PerturbPlan introduces an analytical framework for designing Perturb-seq and TAP-seq experiments, reducing power calculation runtimes by up to seven orders of magnitude and enabling interactive experimental design. www.biorxiv.org/content/10.6...

PerturbPlan: An analytical framework for designing Perturb-seq experiments

CRISPR screens with single-cell RNA-seq readouts provide a powerful tool for characterizing the functions of noncoding elements and genes. However, designing these experiments to balance statistical p...

biorxiv.org

New preprint with @kanishkadey.bsky.social's group. We asked: can you connect what happens to beta cells under nutrient stress in a dish to T2D genetics and dietary patterns in ~46K people? We built a "dish-to-biobank" framework to find out. #StemCells #UKBiobank www.biorxiv.org/content/10.6...

A dish-to-biobank framework links β-cell nutrient-stress programs to genetic and dietary risk for Type 2 Diabetes

Type 2 diabetes (T2D) arises from genetic susceptibility and chronic metabolic stress, but whether these converge on shared molecular programs in human populations remains unclear. Here, we develop a ...

biorxiv.org

Super chuffed to see our latest preprint is out: Polygenic risk of cardiovascular disease manifests in cardiac structure and function 👉 www.medrxiv.org/content/10.6... A collaborative study led by exceptional PhD student Benedetta Felici!

1/🧵 Can transcription factor condensate formation be explained without phase separation? Our new preprint introduces SPARK, a simulation tool that reproduces condensate behavior (clustering, fusion, FRAP) from diffusion & binding kinetics alone. Movie: 60 sec FRAP sim www.biorxiv.org/content/10.6...

Planning a Perturb-seq experiment? Building virtual cells? First step to good models is good data. How many cells to profile? How deeply to sequence? What statistical power? Check out PerturbPlan — new tool from Ziang Niu in Katsevich Lab www.perturbplan.com www.biorxiv.org/content/10.6...

Exciting single cell eQTL study of IBD — showing how cell type resolved QTLs at scale find colocalized signals for over half of the GWAS signals www.nature.com/articles/s41...

Cell-type-resolved genetic variation shapes inflammatory bowel disease risk - Nature

Single-cell mapping of cis-expression quantitative trait loci in inflammatory bowel disease revealed distal, enhancer-enriched variants detected at the cell-type level more frequently co-loc...

links.springernature.com

Out now in Science! Our study challenges long-standing assumptions about transcription factor specificity in eukaryotes. Novel single-molecule measurements of TF behavior in living cells reveal an independence of locus-specific binding from DNA sequence recognition.🧵 www.science.org/doi/10.1126/...

Unstructured transcription factor interactions enable emergent specificity

How intrinsically disordered regions (IDRs) shape chromatin binding and nuclear organization of transcription factors (TFs) remains unclear. We used proximity-assisted photoactivation (PAPA), a single...

science.org

Hello #world, meet 1,000× Expansion Microscopy. A small gel would grow to the size of an Olympic swimming pool, while amino-acid-scale distances become visible with ordinary light microscopy. Led by Helena Hu from @eboyden3.bsky.social's lab, in collab with us. Story: www.biorxiv.org/content/10.6...

I'm excited to share that our work studying gene dosage response curves (GDRCs) is now out in Cell Genomics (@cellpress.bsky.social). www.cell.com/cell-genomic... [1/n]

Buffering of gene dosage response curves for human complex traits

Milind et al. explore why loss-of-function variants and duplications tend to have average effects in the same direction on 94 complex traits. Using gene dosage response curves (GDRCs), they gather evi...

cell.com

How can researchers access and build on IGVF resources?  In this workshop presentation, Michael Love, PhD, highlights the IGVF data portal, catalog, APIs, and computational tools supporting reproducible functional genomics research. youtu.be/W6Mr7O7gUNY

Accessing and Building on the IGVF Data Portal and Catalog

YouTube video by Impact of Genomic Variation on Function

youtu.be

🚨🧪🧵URGENT INPUT NEEDED: NIH asks input for next strategic plan-including emphasis on non-animal models (NAMs) to replace animals. Per NIH insider, anti-animal responses now outnumber scientists 200-700x. Please please provide input. Deadline: May 26, 11:59 PM ET. grants.nih.gov/news-events/...

Now out @natbiotech.nature.com ! Do lncRNAs commonly bind 1000s of genomic sites? Maybe they do, but the dozens of studies that report genomic binding maps of lncRNAs are deeply flawed, with probes binding suprious DNA sites rather than RNA-bound ones.

Igor Ulitsky@igorulitsky.bsky.social · 11mo ago

A preprint‼️that's bound to ruffle some 🪶 "Widespread DNA off-targeting confounds studies of RNA chromatin occupancy" led by our Micah Goldrich and Louis Delhaye from Pieter Mestdagh in Ghent. TL;DR we show that many of lncRNA chromatin occupancy obtained are flawed www.biorxiv.org/content/10.1...